COMBINATION THERAPIES COMPRISING A QUINOXALINE INHIBITOR OF PI3K-ALPHA FOR USE IN THE TREATMENT OF CANCER

Description

Cross-Reference to Related Applications

[0001] The Applicants claim priority under 35 U.S.C. 119(e) to copending Provisional Application No. 60/923,164 filed on April 11, 2007.

FIELD OF THE INVENTION

[0002] This invention relates to the use in a method of treating cancer with a compound that inhibits lipid kinase enzymatic activity and the resultant modulation of cellular activities (such as proliferation, differentiation, programmed cell death, migration, chemoinvasion and metabolism) in combination with anticancer agents.

BACKGROUND OF THE INVENTION

[0003] Improvements in the specificity of agents used to treat various disease states such as cancer, metabolic, and inflammatory diseases is of considerable interest because of the therapeutic benefits which would be realized if the side effects associated with the administration of these agents could be reduced. Traditionally, dramatic improvements in the treatment of cancer are associated with identification of therapeutic agents acting through novel mechanisms.

[0004] Phosphatidylinositol 3-kinase (PI3K or PIK3CA) is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. PTEN, a tumor suppressor which inhibits cell growth through multiple mechanisms, can dephosphorylate PIP3, the major product of PIK3CA. PIP3, in turn, is required for translocation of protein kinase B (AKT1, PKB) to the cell membrane, where it is phosphorylated and activated by upstream kinases. The effect of PTEN on cell death is mediated through the PIK3CA/AKT1 pathway.

[0005] PI3Kα has been implicated in the control of cytoskeletal reorganization, apoptosis, vesicular trafficking, proliferation and differentiation processes. Increased copy number and expression of PIK3CA or activating mutations in the p110a catalytic subunit of PIK3CA are associated with a number of malignancies such as ovarian cancer (Campbell et al., Cancer Res 2004, 64, 7678-7681; Levine et al., Clin Cancer Res 2005, 11, 2875-2878; Wang et al., Hum Mutat 2005, 25, 322; Lee et al., Gynecol Oncol 2005, 97, 26-34), cervical cancer, breast cancer (Bachman, et al. Cancer Biol Ther 2004, 3, 772-775; Levine, et al., supra; Li et al., Breast Cancer Res Treat 2006, 96, 91-95; Saal et al., Cancer Res 2005, 65, 2554-2559; Samuels and Velculescu, Cell Cycle 2004, 3, 1221-1224), colorectal cancer (Samuels, et al. Science 2004, 304, 554; Velho et al. EurJ Cancer 2005, 41, 1649-1654), endometrial cancer (Oda et al. Cancer Res. 2005, 65, 10669-10673), gastric carcinomas (Byun et al., Int J Cancer 2003, 104, 318-327; Li et al., supra; Velho et al., supra; Lee et al., Oncogene 2005, 24, 1477-1480), hepatocellular carcinoma (Lee et al., id.), small and non-small cell lung cancer (Tang et al., Lung Cancer 2006, 51, 181-191; Massion et al., Am J Respir Crit Care Med 2004, 170, 1088-1094), thyroid carcinoma (Wu et al., J Clin Endocrinol Metab 2005, 90, 4688-4693), acute myelogenous leukemia (AML) (Sujobert et al., Blood 1997, 106, 1063-1066), chronic myelogenous leukemia (CML) (Hickey and Cotter J Biol Chem 2006, 281, 2441-2450), and glioblastomas (Hartmann et al. Acta Neuropathol (Berl) 2005, 109, 639-642; Samuels et al., supra).

[0006] The prior art already discloses quinaxoline derivatives as PI3K inhibitors. Indeed document WO2007/023186 discloses fused-pyrazine derivatives, in particular quinaxoline derivatives as P13K inhibitors and document WO2007/044729, published in the priority period of the present disclosure, also discloses the present compounds of formula (I), as P13K inhibitors, in combination with a chemotherapeutic agent, surgery and radiation.

[0007] In view of the important role of PI3K-α in biological processes and disease states, inhibitors and/or modulators of this lipid kinase are desirable. In addition, it is well established that combining treatments with different mechanisms of action often leads to enhanced anti-tumor activity as compared to single treatments administered alone. This is true for combinations of chemotherapies (e.g. Kyrgiou M. et. al. J Natl Cancer Inst 2006, 98, 1655) and combinations of antibodies and chemotherapy (e.g. Pasetto LM et. al. Anticancer Res 2006, 26, 3973.

[0008] For example, activation of the PI3K pathway contributes to the resistance of human tumor cells to a wide variety of chemotherapeutic agents, including microtubule stabilizing agents such as taxol (Brognard, J., et. al. Cancer Res 2001, 61, 3986-3997; Clark, A. S., et. al. Mol Cancer Ther 2002, 1, 707-717; Kraus, A. C., et. al. Oncogene 2002, 21, 8683-8695; Krystal, G. W., et. al. Mol Cancer Ther 2002, 1, 913-922; and Yuan, Z. Q., et. al. J Biol Chem 2003, 278, 23432-23440). Taxol is widely used to treat advanced cancers including prostate carcinomas, which frequently harbor deletions in the PTEN gene, resulting in elevated signaling downstream of PI3K. A number of preclinical studies suggest that inhibiting signaling downstream of PI3K restores or enhances the ability of chemotherapeutic agents such as taxol to kill tumor cells (Brognard, J., et. al. Cancer Res 2001, 61, 3986-3997; Clark, A. S., et. al. Mol Cancer Ther 2002, 1, 707-717; Kraus, A. C., et. al. Oncogene 2002, 21, 8683-8695; Krystal, G. W., et. al. Mol Cancer Ther 2002, 1, 913-922; and Saga, Y., et. al. Clin Cancer Res 2002, 8, 1248-1252).

[0009] Rapamycin, another chemotherapeutic agent, is a potent inhibitor of the mTOR/Raptor complex. Inhibition of mTOR/Raptor prevents p70S6K and S6 phosphorylation, but also leads to relief of a negative feedback loop emanating from p70S6K that serves to downregulate PI3K (Sarbassov, D. D., et. al. Science 2005, 307, 1098-1101). As a result, rapamycin treatment can lead to upregulation of PI3K and increased phosphorylation of AKT (O'Donnell, A., et. al. paper presented at Proc Am Soc Clin Oncol. 2003; and O'Reilly, K. E., et. al. Cancer Res 2006, 66, 1500-1508). Thus, combining rapamycin with inhibitors of PI3K can enhance the efficacy of rapamycin (Powis, G. et. al. Clinical Cancer Research 2006, 12, 2964-2966; Sun, S.-Y., et. al. Cancer Research 2005, 65, 7052-7058).

[0010] A growing body of clinical and preclinical data indicates that activation of the PI3K pathway confers resistance to EGFR inhibitors such as erlotinib (Bianco, R., et. al. Oncogene 2003, 22, 2812-2822; Chakravarti, A., et. al. Cancer Res 2002, 62, 200-207; and Janmaat, M. L., et. al. Clin Cancer Res 2003, 9, 2316-2326). Both NSCLC patients with K-Ras mutations and glioblastoma patients with PTEN deletions fail to respond to erlotinib, potentially because of genetic activation of the PI3K pathway (Mellinghoff, I. K., et. al. N. Eng. J Med. 2006, 353, 2012-2024). Preclinical studies have shown that downregulation of PI3K signaling in EGFR-expressing tumor cells confers increased sensitivity to EGFR inhibitors (Ihle, N. T., et. al. Mol Cancer Ther 2005, 4, 1349-1357). Thus, treating cancer with a PI3K inhibitor in combination with an EGFR inhibitor, such as erlotinib, is desirable.

[0011] Activation of the PI3K pathway also contributes to the resistance of human tumor cells to DNA damaging agents, such as platins. A number of preclinical studies suggest that inhibiting signaling downstream of PI3K restores or enhances the ability of chemotherapeutic agents such as platins to kill tumor cells (Brognard, J., et. al. Cancer Res 2001, 61, 3986-3997; and Yuan, Z. Q., et. al. J Biol Chem 2003, 278, 23432-23440). Carboplatin is widely used to treat advanced cancers including non-small cell lung carcinomas (NSCLC), which frequently harbor activating mutations in the K-Ras gene, resulting in activation of PI3K (Aviel-Ronen S., et. al. Clin Lung Cancer 2006, 8, 30-38). NSCLC patients with K-Ras mutations do not respond to EGFR inhibitors such as Tarceva, and thus represent a significant unmet medical need (Janne PA, et. al. J Clin Oncology 2005, 23, 3227-3234). Thus, treating NSCLC with a DNA-damaging agent such as a platin in combination with an inhibitor of P13K is desirable in light of the lack of efficacious treatments.

[0012] Treatments that combine an inhibitor of PI3K-α with other anti-cancer agents are desirable and needed.

SUMMARY OF THE INVENTION

[0013] The following only summarizes certain aspects of the invention and is not intended to be limiting in nature. These aspects and other aspects and embodiments are described more fully below. In the event of a discrepancy between the express disclosure of this specification and the references mentioned herein, the express disclosure of this specification shall control.

[0014] According to the invention, there is provided a compound which is:

or a tautomer or a single isomer thereof where the compound is optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof; for use in combination with one or more treatments independently selected from one or more chemotherapeutic agents selected from the group consisting of a platin, a taxane, rapamycin, and erlotinib for the treatment of cancer.

[0015] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a compound of Formula I:

or a single isomer thereof where the compound is optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof; or administering a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula I and a pharmaceutically acceptable carrier, excipient, or diluent in combination with one or more treatments independently selected from surgery, one or more chemotherapeutic agents, one or more hormone therapies, one or more antibodies, one or more immunotherapies, radioactive iodine therapy, and radiation, where the Compound of Formula I is that wherein:

W¹, W², W³, and W⁴ are -C(R¹)=; or one or two of W¹, W², W³, and W⁴ are independently -N= and the remaining are -C(R¹)=; and where each R¹ is independently hydrogen, alkyl, haloalkyl, nitro, alkoxy, haloalkoxy, halo, hydroxy, cyano, amino, alkylamino, or dialkylamino;

R⁵¹ is hydrogen or alkyl;

R⁵² is hydrogen or halo;

R⁵⁰, R⁵³, and R⁵⁴ are independently hydrogen, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, nitro, amino, alkylamino, dialkylamino, -N(R⁵⁵)C(O)-C₁-C₆-alkylene-N(R^55a)R^55b, alkylcarbonyl, alkenylcarbonyl, carboxy, alkoxycarbonyl, cyano, alkylthio, -S(O)₂NR⁵⁵R^55a, or alkylcarbonylamino and where R⁵⁵ and R^55b are indepedently hydrogen, alkyl, or alkenyl and R^55a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy; or R⁵³ and R⁵⁴ together with the carbons to which they are attached form a 5- or 6-membered heteroaryl or 5- or 6-membered heterocycloalkyl;

B is phenyl substituted with R^3a and optionally further substituted with one, two, or three R³; or

B is heteroaryl optionally substituted with one, two, or three R³;

R^3a is cyano; hydroxyamino; carboxy; alkoxycarbonyl; alkylamino; dialkylamino; alkylcarbonyl; haloalkoxy; alkylsulfonyl; aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; or

a) -N(R⁷)C(O)-C₁-C₆-alkylene-N(R^7a)(R^7b) where R⁷ is hydrogen, alkyl, or alkenyl and R^7a and R^7b are independently hydrogen, alkyl, alkenyl, hydroxyalkyl, haloalkyl, alkoxy, alkoxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, or arylalkyloxy and where the aryl, cycloalkyl, heterocycloalkyl and heteroaryl rings in R^7a and R^7b (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, amino, alkylamino, dialkylamino, hydroxy, halo, alkoxy, alkylthio, and oxo);

b) -C(O)NR⁸R^8a where R⁸ is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and R^8a is hydrogen, alkyl, alkenyl, hydroxyalkyl, cyanoalkyl, alkoxyalkyl, alkylthioalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl and where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in R^8a (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonyl, and -C(O)H;

c) -NR⁹C(O)R^9a where R⁹ is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and R^9a is hydrogen, C₂-C₆-alkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl; where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in R^9a (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, hydroxy, hydroxyalkyl, halo, haloalkyl, haloalkoxy, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, alkoxycarbonyl, -C(O)H, aryl (optionally substituted with one or two halo), arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cyloalkyl, cyloalkylalkyl, and cycloalkylcarbonyl;

d) -C(O)N(R¹⁰)-C₁-C₆-alkylene-N(R^10a)R^10b where R^10a is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, or hydroxyalkyl and R¹⁰ and R^10b are independently hydrogen, alkyl, alkenyl, haloalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, or hydroxyalkyl;

e) -NR¹¹C(O)NR^11aR^11b where R^11a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy and R¹¹ and R^11b are independently hydrogen, alkyl, alkenyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl;

f) -C(O)R¹² where R¹² is heterocycloalkyl optionally substituted with 1, 2, or 3 groups selected from alkyl, oxo, amino, alkylamino, and heterocycloalkylalkyl;

g) -NR¹³C(O)OR^13a where R¹³ is hydrogen, alkyl, or alkenyl and R^13a is aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aryl, or arylalkyl;

h) -C(O)N(R¹⁴)N(R^14a)(R^14b) where R¹⁴, R^14a, and R^14b are independently hydrogen, alkyl, or alkenyl;

i) -S(O)₂N(R¹⁵)-C₁-C₆-alkylene-N(R^15a)R^15b where R¹⁵, R^15a, and R^15b are independently hydrogen, alkyl, or alkenyl;

j) -C(O)N(R¹⁶)-C₁-C₆-alkylene-C(O)OR^16a where R¹⁶ is hydrogen, alkyl, or alkenyl and R^16a is alkyl or alkenyl;

k) heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl;

l) -N(R¹⁷)-C(=N(R^17b)(R^17a))(NR^17cR^17d) where R¹⁷, R^17a, R^17b, R^17c, and R^17d are independently hydrogen, alkyl, or alkenyl;

m) -N(R¹⁸)C(O)-C₁-C₆-alkylene-N(R^18b)C(O)R^18a where R^18a is hydrogen, alkyl, alkenyl, or alkoxy and R¹⁸ and R^18b are independently hydrogen, alkyl, or alkenyl;

n) -C(O)N(R¹⁹)-C₁-C₆-alkylene-C(O)R^19a where R¹⁹ is hydrogen, alkyl, or alkenyl and R^19a is amino, alkylamino, dialkylamino, or heterocycloalkyl;

o) -N(R²⁰)C(O)-C₁-C₆-alkylene-C(O)R^20a where R²⁰ is hydrogen, alkyl, or alkenyl and R^20a is cycloalkyl or heterocycloalkyl;

p) -NR²¹S(O)₂-C₁-C₆-alkylene-N(R^21b)R^21a where R²¹ is hydrogen, alkyl, or alkenyl and R^21a and R^21b are independently hydrogen, alkyl, or alkenyl;

q) -N(R²²)C(O)-C₁-C₆-alkylene-N(R^22b)-N(R^22c)(R^22a) where R²², R^22a and R^22b are independently hydrogen, alkyl, or alkenyl;

r) -C₀-C₆-alkylene-N(R²³)-C₁-C₆-alkylene-N(R^23b)R^23a where R²³, R^23a and R^23b are independently hydrogen, alkyl, or alkenyl; or

s) -NR²⁴C(O)-C₁-C₆-alkylene-OR^24a where R²⁴ is hydrogen, alkyl, or alkenyl and R^24a is
alkoxyalkyl or aryl optionally substituted with one or two halo or alkyl; and
where each of the alkylene in R^3a is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, amino, alkylamino, and dialkylamino; and each R³ (when R³ is present) is independently alkyl; alkenyl; alkynyl; halo; hydroxy; oxo;
alkoxy; cyano; hydroxyamino; carboxy; alkoxycarbonyl; amino; alkylamino; dialkylamino; alkylcarbonyl; haloalkoxy; alkylsulfonyl; aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; or

a) -N(R⁷)C(O)-C₁-C₆-alkylene-N(R^7a)(R^7b) where R⁷ is hydrogen, alkyl, or alkenyl and R^7a and R^7b are independently hydrogen, alkyl, alkenyl, hydroxyalkyl, haloalkyl, alkoxy, alkoxyalkyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, arylalkyl, or arylalkyloxy and where the aryl, cycloalkyl, heterocycloalkyl and heteroaryl rings in R^7a and R^7b (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, amino, alkylamino, dialkylamino, hydroxy, halo, alkoxy, alkylthio, and oxo);

b) -C(O)NR⁸R^8a where R⁸ is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and R^8a is hydrogen, alkyl, alkenyl, hydroxyalkyl, cyanoalkyl, alkoxyalkyl, alkylthioalkyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl and where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in R^8a (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxy, hydroxyalkyl, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, alkoxycarbonyl, and -C(O)H;

c) -NR⁹C(O)R^9a where R⁹ is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or haloalkoxy and R^9a is hydrogen, C₂-C₆-alkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, aryl, or arylalkyl; where the aryl, cycloalkyl, heteroaryl, and heterocycloalkyl rings in R^9a (either alone or as part of arylalkyl, cycloalkylalkyl, heterocycloalkylalkyl and heteroarylalkyl) are independently optionally substituted with 1, 2, or 3 groups independently selected from alkyl, alkenyl, alkoxy, hydroxy, hydroxyalkyl, halo, haloalkyl, haloalkoxy, oxo, amino, alkylamino, dialkylamino, alkylcarbonyl, alkoxycarbonyl, -C(O)H, aryl (optionally substituted with one or two halo), arylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, cyloalkyl, cyloalkylalkyl, and cycloalkylcarbonyl;

d) -C(O)N(R¹⁰)-C₁-C₆-alkylene-N(R^10a)R^10b where R^10a is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, haloalkyl, or hydroxyalkyl and R¹⁰ and R^10b are independently hydrogen, alkyl, alkenyl, haloalkyl, or hydroxyalkyl;

e) -NR¹¹C(O)NR^11aR^11b where R^11a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy and R¹¹ and R^11b are independently hydrogen, alkyl, alkenyl, aminoalkyl, alkylaminooalkyl, dialkylaminoalkyl;

f) -C(O)R¹² where R¹² is heterocycloalkyl optionally substituted with 1, 2, or 3 groups selected from alkyl, oxo, amino, alkylamino, and heterocycloalkylalkyl;

g) -NR¹³C(O)OR^13a where R¹³ is hydrogen, alkyl, or alkenyl and R^13a is aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aryl, or arylalkyl);

h) -C(O)N(R¹⁴)N(R^14a)(R^14b) where R¹⁴, R^14a, and R^14b are independently hydrogen, alkyl, or alkenyl;

i) -S(O)₂N(R¹⁵)-C₁-C₆-alkylene-N(R^15a)R^15b where R¹⁵, R^15a, and R^15b are independently hydrogen, alkyl, or alkenyl;

j) -C(O)N(R¹⁶)-C₁-C₆-alkylene-C(O)OR^16a where R¹⁶ is hydrogen, alkyl, or alkenyl and R^16a is alkyl or alkenyl;

k) heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl;

l) -N(R¹⁷)-C(=N(R^17b)(R^17a))(NR^17cR^17d) where R¹⁷, R^17a, R^17b, R^17c, and R^17d are independently hydrogen, alkyl, or alkenyl;

m) -N(R¹⁸)C(O)-C₁-C₆-alkylene-N(R^18b)C(O)R^18a where R^18a is hydrogen, alkyl, alkenyl, or alkoxy and R¹⁸ and R^18b are independently hydrogen, alkyl, or alkenyl;

n) -C(O)N(R¹⁹)-C₁-C₆-alkylene-C(O)R^19a where R¹⁹ is hydrogen, alkyl, or alkenyl and R^19a is amino, alkylamino, dialkylamino, or heterocycloalkyl;

o) -N(R²⁰)C(O)-C₁-C₆-alkylene-C(O)R^20a where R²⁰ is hydrogen, alkyl, or alkenyl and R^20a is cycloalkyl or heterocycloalkyl;

p) -NR²¹S(O)₂-C₁-C₆-alkylene-N(R^21b)R^21a where R²¹ is hydrogen, alkyl, or alkenyl and R^21a and R^21b are independently hydrogen, alkyl, or alkenyl;

q) -N(R²²)C(O)-C₁-C₆-alkylene-N(R^22b)-N(R^22c)(R^22a), where R²², R^22a and R^22b are independently hydrogen, alkyl, or alkenyl;

r) -C₀-C₆-alkylene-N(R²³)-C₁-C₆-alkylene-N(R^23b)R^23a where R²³, R^23a and R^23b are independently hydrogen, alkyl, or alkenyl; or

s) NR²⁴C(O)-C₁-C₆-akylene-OR^24a where R²⁴ is hydrogen, alkyl, or alkenyl and R^24a is alkoxyalkyl or aryl optionally substituted with one or two halo or alkyl;

wherein each of the alkylene in R³ is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, amino, alkylamino, and dialkylamino; and provided that when R⁵⁰ and R⁵² are hydrogen, R⁵¹ is hydrogen or methyl, R⁵³ is hydrogen or methoxy, and R⁵⁴ is hydrogen or methoxy, then B is not 2,3-dihydro-1,4-benzodioxinyl, thien-2-yl, or thien-2-yl substituted with one R³ where R³ is halo.

[0016] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a compound of Formula II:

or a pharmaceutically acceptable salt or solvate, thereof; or administering a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula II and a pharmaceutically acceptable carrier, excipient, or diluent in combination with one or more treatments independently selected from surgery, one or more chemotherapeutic agents, one or more of the hormone therapies, one or more of the antibodies, one or more immunotherapies, radioactive iodine therapy, and radiation wherein the Compound of Formula I is that wherein: W¹, W², W³, and W⁴ are -C(R^1a)=; or one or two of W¹, W², W³, and W⁴ are independently -N= and the remaining are -C(R^1a)=;
X¹ is -N(R^5a)-;
A is aryl, -S(O)₂-aryl, heteroaryl, cycloalkyl, heterocycloalkyl, halo, haloalkyl, haloalkoxy, alkyl, alkoxy, or -alkyl-N(R⁷)R^7a, where each of the aryl, heteroaryl, cycloalkyl, heterocycloalkyl, alkyl and alkoxy groups, each either alone or as part of another group within A, are independently optionally substituted with one, two, three, or four R^2a; or
B¹ is aryl, arylalkyl, alkyl, heteroaryl, or heteroaryalkyl, wherein each of the aryl, heteroaryl and alkyl groups are independently optionally substituted with one, two, three, or four R^3d;
each R^1a is independently selected from hydrogen, alkoxy, alkyl, nitro, halo, cyano, and -C₀-C₆-alkyl-N(R⁷)R^7a, wherein each of the alkyl and alkoxy groups is optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, alkoxy, halo, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -N(R⁸)R^8a, and -C(O)OR⁶;
each R^2a (when R^2a is present) is independently selected from alkyl, alkenyl, -alkenyl-C(O)OR⁶, -OR⁶, -N(R⁷)C(O)R⁶, -N(R⁷)C(O)-C₀-C₆ alkyl-N(R^7b)R^7a, -OC(O)-C₀-C₆ alkyl-N(R⁷)R^7a, -N(R⁷)C(O)-C₁-C₆ alkylC(O)OR⁶, C₀-C₆-alkyl-C(O)R⁶, oxo, dioxo, -S(O)₂-N(R⁷)R^7a, -C(O)OR⁶, -CH(R⁶)₂-C(O)OR⁶, -S(O)₂R⁶, cycloalkyl, heterocycloalkyl, heteroaryl, -C(O)N(R⁷)-alkyl-OR⁶, -C₀-C₆ alkyl-C(O)N(R⁷)-C₀-C₆-alkyl-C(O)OR⁶, -C₀-C₆-alkyl-C(O)N(R⁷)R^7a, aryl, arylalkyl, -S-(C₁-C₆ alkyl), halo, oxo, nitro, -SCN, cyano, and -C₀-C₆ alkyl-N(R⁷)R^7a, wherein each of the alkyl (including, for example the alkyl within alkoxy), aryl, cycloalkyl, heterocycloalkyl, and heteroaryl groups, either alone or as part of another group within R², is independently optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, halo, haloalkyl, haloalkoxy, oxo, nitro, cyano, hydroxy, -N(R⁸)R^8a, alkoxy, and -C(O)OR⁹;
each R^3d (when R^3d is present) is independently oxo, nitro, halo, cyano, alkyl, alkenyl, alkynyl, alkoxy, C₃-C₆-cycloalkyl, -C₀-C₆-alkyl-heterocycloalkyl, -C₀-C₆ alkyl-N(R⁷)C(O)-C₀-C₆-alkyl-N(R^7b)R^7a, -C₀-C₆ alkyl-N(R⁷)C(O)-C₀-C₆-alkyl-N(R^7b)C(O)R^7a, -C₀-C₆ alkyl-C(O)-C₀-C₆-alkyl-N(R⁷)R^7a, -C₀-C₆-alkyl-C(O)N(R⁷)-C₀-C₆-alkyl-N(R^7b)R^7a, -C₀-C₆-alkyl-C(O)N(R⁷)-C₁-C₆alkylC(O)OR^7a, -C₀-C₆ alkyl-N(R⁷)C(O)-C₀-C₆-alkyl-(R^7a), -C₀-C₆ alkyl-N(R⁷)-C₀-C₆-alkyl-N(R^7b)R^7a, -C₀-C₆ alkyl-N(R⁷)C(O)-C₀-C₆-alkyl-N(R^7b)-N(R^7c)R^7a, -C₀-C₆ alkyl-N(R⁷)C(O)O-C₀-C₆-alkyl-aryl, -C₀-C₆ alkyl-C(O)N(R⁷)-C₀-C₆-alkyl-N(R^7b)R^7a, -C₀-C₆ alkyl-N(R⁷)-C₀-C₆alkyl-C(=N(R^7b)(R^7a))(NR^7cR^7d), -C₀-C₆-alkyl-aryl, -C₀-C₆-alkyl-heteroaryl, -C₀-C₆ alkyl-heterocycloalkyl, -O-C₀-C₆ alkyl-N(R⁷)R^7a, -C₀-C₆ alkyl-OR₆, -C₀-C₆ alkyl-C(O)OR⁶, C₀-C₆-alkyl-N(R⁷)R^7a, -C₀-C₆ alkyl-C(O)NR₇R^7a, -C₀-C₆ alkyl-C(O)R⁷, -SR₇, -S(O)₂R₇, -S(O)₃R₇, -S(O)R⁷, -SO₂N(R⁷)R^7a, -SO₂N(R⁷)-C₀-C₆ alkyl-N(R^7b)R^7a, -C₀-C₆-alkyl-N(R⁷)-aryl, -C₀-C₆-alkyl-N(R⁷)-heteroaryl, -C₀-C₆-alkyl-N(R⁷)-heterocycloalkyl, -C₀-C₆-alkyl-C(O)N(R⁷)-C₀-C₆-alkyl-cycloalkyl, C₀-C₆-alkyl-C(O)N(R⁷)-C₀-C₆-alkyl-aryl, C₀-C₆ alkyl-C(O)N(R⁷)-C₀-C₆ alkyl-heteroaryl, C₀-C₆ alkyl-C(O)N(R⁷)-C₀-C₆-alkyl-heterocycloalkyl, -C₀-C₆-alkyl-N(R⁷)C(O)-C₀-C₆-alkyl-cycloalkyl, -C₀-C₆-alkyl-N(R⁷)C(O)-C₀-C₆-alkyl-aryl, C₀-C₆-alkyl-N(R⁷)C(O)-C₀-C₆-alkyl-heteroaryl, -C₀-C₆-alkyl-N(R⁷)C(O)-C₀-C₆-alkyl-heterocycloalkyl, C₀-C₆-alkyl-N(R⁷)C(O)-C₀-C₆-alkyl-heterocycloalkyl-aryl, -N(R⁷)C(O)OR⁶, or -NHC(O)H, wherein each of the alkyl, alkenyl, cycloalkyl, aryl, (including, for example the alkyl within alkoxy), heterocycloalkyl, and heteroaryl groups, either alone or as part of another group within R^3d, is independently optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, alkenyl, -C₀-C₆-alkyl-OR⁹, cycloalkyl, halo, haloalkyl, haloalkoxy, -C(O)R⁹, nitro, cyano, oxo, -C₀-C₆-alkyl-N(R⁸)R^8a, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, -C(O)OR⁹, alkylthio, and hydroxyalkyl;
R⁴ is hydrogen, aryl, -C₀-C₆-alkyl-N(R⁷)R^7a, alkoxy, or C₁-C₆ alkyl, wherein each of the alkyl and aryl groups, either alone or as part of another group in R⁴, is independently optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, halo, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -N(R⁸)R^8a, alkoxy, and -C(O)OR⁶; or
R⁴ and X¹ together with the atoms to which they are attached form a heterocycloalkyl or heteroaryl group, wherein R^5a is absent when X is -N(R^5a)-, wherein each of the heterocycloalkyl or heteroaryl is optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, halo, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -N(R⁷)R^7a, alkoxy, and -C(O)OR⁶;
R^5a is hydrogen, -C₁-C₆ alkyl-N(R⁷)R^7a, alkoxy, alkyl, or aryl, wherein each of the alkyl and aryl is optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, halo, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -N(R⁸)R^8a, C₁-C₆ alkoxy, or -C(O)OR⁶; or
R^5a and R⁴ together with the atoms to which they are attached form a heterocycloalkyl or heteroaryl group, wherein the heterocycloalkyl and heteroaryl is optionally substituted with 1, 2, 3, 4, or 5 groups selected from alkyl, halo, haloalkyl, haloalkoxy, nitro, cyano, hydroxy, -N(R⁷)R^7a, C₁-C₆ alkoxy, and -C(O)OR⁶;
R⁶ and R⁹ are independently hydrogen, hydroxy, alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, heteroarylalkyl, or aryl, each alkyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl, either alone or as part of another group within R⁶ and R⁹, is independently optionally substituted with 1, 2, 3, 4,
or 5 groups independently selected from amino, hydroxy, alkoxy, alkyl, and halo; and R⁷, R^7a R^7b, R^7c, R^7d, R⁸, and R^8a are independently hydrogen, alkyl, alkenyl, hydroxy, alkyloxy, alkenyloxy, -O-C₀-C₆ alkyl-aryl, -C₀-C₆ alkyl-C(O)OR⁶, -C₀-C₆ alkyl-C(O)R⁶, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, or heterocycloalkylalkyl, wherein each of the alkyl, aryl, heteroaryl, and heterocycloalkyl, either alone or part of another group within R⁷, R^7a R^7b, R^7c, R^7d, R⁸, and R^8a is independently optionally substituted with 1, 2, 3, 4, or 5 groups selected from amino, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, -S-C₁-C₆ alkyl, cyano, nitro, hydroxy, C₁-C₆ alkoxy, C₁-C₆ alkyl, halo, aryl, heterocycloalkylalkyl, and heteroaryl optionally substituted with one or two C₁-C₆ alkyl.

DETAILED DESCRIPTION OF THE INVENTION

Abbreviations and Definitions

[0017] The following abbreviations and terms have the indicated meanings throughout:

Abbreviation	Meaning
br	broad
°C	degrees Celsius
CBZ	CarboBenZoxy = benzyloxycarbonyl
d	doublet
dd	doublet of doublet
dt	doublet of triplet
EI	Electron Impact ionization
Et	Ethyl
g	gram(s)
GC	gas chromatography
h or hr	hour(s)
HPLC	high pressure liquid chromatography
L	liter(s)
M	molar or molarity
m	Multiplet
mg	milligram(s)
MHz	megahertz (frequency)
Min	minute(s)
mL	milliliter(s)
mM	Millimolar
mmol	millimole(s)
mol	mole(s)
MS	mass spectral analysis
N	normal or normality
nM	Nanomolar
NMR	nuclear magnetic resonance spectroscopy
q	Quartet
RT	Room temperature
s	Singlet
s-	Secondary
t-	Tertiary
t or tr	Triplet
TFA	trifluoroacetic acid
THF	Tetrahydrofuran
µL	microliter(s)
µM	Micromole(s) or micromolar

Definitions for a Compound of Formula I, Ia, and II

[0018] The symbol "-" means a single bond, "=" means a double bond, "≡" means a triple bond, and "---" means a single bond and optionally a double bond. When chemical structures are depicted or described, unless explicitly stated otherwise, all carbons are assumed to have hydrogen substitution to conform to a valence of four.

[0019] "Administration" and variants thereof (e.g., "administering" a compound) in reference to a compound of the invention means introducing the compound or a prodrug of the compound into the system of the animal in need of treatment. When a compound of the invention or prodrug thereof is provided in combination with one or more other active agents (e.g., surgery, radiation, and chemotherapy, etc.), "administration" and its variants are each understood to include concurrent and sequential introduction of the compound or prodrug thereof and other agents.

[0020] "Alkenyl" or "lower alkenyl" means a straight or branched hydrocarbon radical having from 2 to 6 carbon atoms and at least one double bond and includes ethenyl, propenyl, 1-but-3-enyl, 1-pent-3-enyl, 1-hex-5-enyl and the like.

[0021] "Alkenylcarbonyl" means a C(O)R group where R is alkenyl, as defined herein.

[0022] "Alkenyloxy" or "lower alkenyloxy" means an -OR group where R is alkenyl, as defined herein. Representative examples include methoxy, ethoxy, 1-methoxyprop-1-en-3-yl, propoxy, isopropoxy, cyclopropyloxy, cyclohexyloxy and the like.

[0023] "Alkoxy" or "lower alkoxy" means an -OR group where R is alkyl, as defined herein. Representative examples include methoxy, ethoxy, 1-methoxyprop-1-en-3-yl, propoxy, isopropoxy, cyclopropyloxy, cyclohexyloxy and the like.

[0024] "Alkoxyalkyl" means an alkyl group, as defined herein, substituted with one, two, or three alkoxy groups, as defined herein.

[0025] "Akoxycarbonyl" means a -C(O)OR group where R is alkyl as defined herein.

[0026] "Alkoxyycarbonylalkyl" means an alkyl group, as defined herein, substituted with one, two, or three alkoxycarbonyl groups, as defined herein.

[0027] "Alkyl" or "lower alkyl" means a linear or branched hydrocarbon group having one to six carbon atoms. Examples of lower alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, s-butyl, t-butyl, isobutyl, pentyl, hexyl and the like. A "C₀" alkyl (as in "C₀-C₆-alkyl") is a covalent bond. "C₆ alkyl" refers to, for example, n-hexyl, iso-hexyl, and the like.

[0028] "Alkylamino" means a -NHR radical where R is alkyl as defined herein, or an N-oxide derivative thereof, e.g., methylamino, ethylamino, n-, iso-propylamino, n-, iso-, tert-butylamino, or methylamino-N-oxide, and the like.

[0029] "Alkylaminoalkyl" means an alkyl group substituted with one or two alkylamino groups, as defined herein.

[0030] "Alkylaminoalkyloxy" means an -OR group where R is alkylaminoalkyl, as defined herein.

[0031] "Alkylcarbonyl" means a C(O)R group where R is alkyl, as defined herein.

[0032] "Alkylcarbonylamino" means a -NRC(O)R' group where R is hydrogen or alkyl, as defiend herein, and R' is alkyl, as defiend herein.

[0033] "Alkylene" refers to straight or branched divalent hydrocarbon, containing no unsaturation and having from two to eight carbon atoms. Examples of alkylene include ethdiyl (-CH₂CH₂-), prop-1,3-diyl (-CH₂CH₂CH₂-), 2,2-dimethylprop-1,3-diyl (-CH₂C(CH₃)₂CH₂-), and the like.

[0034] "Alkylsulfonyl" means a -S(O)₂R group where R is lakyl, as defined herien.

[0035] "Alkylthio" means a -SR group where R is alkyl, as defined herein. Examples of alkylthio include methylthio and ethylthio, and the like.

[0036] "Alkylthioalkyl" means an alkyl group substituted with one or two alkylthio groups, as defined herein, e.g. 2-(methylthio)-ethyl and 2-(ethylthio)-ethyl.

[0037] "Alkynyl" or "lower alkynyl" means a straight or branched hydrocarbon radical having from 2 to 6 carbon atoms and at least one triple bond and includes ethynyl, propynyl, butynyl, pentyn-2-yl and the like.

[0038] "Amino" means a -NH₂.

[0039] "Aminoalkyl" means an alkyl group subsitutted with at least one, for example one, two, or three, amino groups.

[0040] "Aminoalkyloxy" means an -OR group where R is aminoalkyl, as defined herein.

[0041] "Aryl" means a monovalent six- to fourteen-membered, mono- or bi-carbocyclic ring, wherein the monocyclic ring is aromatic and at least one of the rings in the bicyclic ring is aromatic. Representative examples include phenyl, naphthyl, and indanyl, and the like.

[0042] "Arylalkyl" means an alkyl group, as defined herein, subsituted with one or two aryl groups, as defined herein. Examples include benzyl, phenethyl, phenylvinyl, phenylallyl and the like.

[0043] "Aryloxy"means a -OR group where R is aryl as defined herein.

[0044] "Arylalkyloxy" means a -OR group where R is arylalkyl as defined herein.

[0045] "Arylsulfonyl" means a -SO₂R group where R is aryl as defined herein.

[0046] "Carboxyalkyl" means an alkyl group, as defined herein, substituted with one, two, or three -C(O)OH groups.

[0047] "Carboxy ester" means a -C(O)OR group where R is lower alkyl, lower alkenyl, lower alkynyl, cycloalkyl, aryl or arylalkyl, each of which is defined herein. Representative examples include methoxycarbonyl, ethoxycarbonyl, and benzyloxycarbonyl, and the like.

[0048] "Cyanoalkyl" means an alkyl, alkenyl, or alkynyl radical, as defined herein, substituted with at least one, for example one, two, or three, cyano groups.

[0049] "Cycloalkyl" means a monocyclic or polycyclic hydrocarbon radical having three to thirteen carbon atoms. The cycloalkyl can be saturated or partially unsaturated, but cannot contain an aromatic ring. Cycloalkyl includes fused, bridged, and spiro ring systems. Examples of such radicals include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

[0050] "Cycloalkylalkyl" means alkyl group substituted with one or two cycloalkyl groups, as defined herein. Representative examples include cyclopropylmethyl and 2-cyclobutyl-ethyl, and the like.

[0051] "Cycloalkylcarbonyl" means a -C(O)R group where R is cycloalkyl as defined herein.

[0052] "Dialkylamino" means a -NRR' radical where R and R' are independently alkyl as defined herein, or an N-oxide derivative, or a protected derivative thereof, e.g., dimethylamino, diethylamino, N,N-methylpropylamino or N,N-methylethylamino, and the like.

[0053] "Dialkylaminoalkyl" means an alkyl group substituted with one or dialkylamino groups, as defined herein.

[0054] "Dialkylaminoalkyloxy" means an -OR group where R is dialkylaminoalkyl, as defined herein.

[0055] "Fused ring system" and "fused ring" refer to a polycyclic ring system that contains bridged or fused rings; that is, where two rings have more than one shared atom in their ring structures. In this application, fused-polycyclics and fused ring systems are not necessarily all aromatic ring systems. Typically, but not necessarily, fused-polycyclics share a vicinal set of atoms, for example naphthalene or 1,2,3,4-tetrahydro-naphthalene. A spiro ring system is not a fused-polycyclic by this definition, but fused polycyclic ring systems of the invention may themselves have spiro rings attached thereto via a single ring atom of the fused-polycyclic. In some examples, as appreciated by one of ordinary skill in the art, two adjacent groups on an aromatic system may be fused together to form a ring structure. The fused ring structure may contain heteroatoms and may be optionally substituted with one or more groups. It should additionally be noted that saturated carbons of such fused groups (i.e. saturated ring structures) can contain two substitution groups.

[0056] "Haloalkoxy" means an -OR' group where R' is haloalkyl as defined herein, e.g., trifluoromethoxy or 2,2,2-trifluoroethoxy, and the like.

[0057] "Haloalkoxyalkyl" means an alkyl group, as defined herein, substituted with one, two, or three haloalkoxy, as defined herein.

[0058] "Halogen" or "halo" means fluoro, chloro, bromo and iodo.

[0059] "Haloalkenyl means an alkenyl group, as defined herein, substituted with one or more halogens, for example one to five halo atoms.

[0060] "Haloalkyl" means an alkyl group, as defined herein, substituted with one or more halogens, for example one to five halo atoms. Representative examples includes 2,2-difluoroethyl, trifluoromethyl, and 2-chloro-1-fluoroethyl, and the like.

[0061] "Heteroaryl" means a monocyclic, fused bicyclic, or fused tricyclic, monovalent radical of 5 to 14 ring atoms containing one or more, for example one, two, three, or four ring heteroatoms independently selected from -O-, -S(O)_n- (n is 0, 1, or 2), -N-, -N(R^x)-, and the remaining ring atoms being carbon, wherein the ring comprising a monocyclic radical is aromatic and wherein at least one of the fused rings comprising a bicyclic or tricyclic radical is aromatic. One or two ring carbon atoms of any nonaromatic rings comprising a bicyclic or tricyclic radical may be replaced by a -C(O)-, -C(S)-, or -C(=NH)- group. R^x is hydrogen, alkyl, hydroxy, alkoxy, acyl, or alkylsulfonyl. Fused bicyclic radical includes bridged ring systems. Unless stated otherwise, the valency may be located on any atom of any ring of the heteroaryl group, valency rules permitting. In particular, when the point of valency is located on the nitrogen, R^x is absent. In another embodiment, the term heteroaryl includes, but is not limited to, 1,2,4-triazolyl, 1,3,5-triazolyl, phthalimidyl, pyridinyl, pyrrolyl, imidazolyl, thienyl, furanyl, indolyl, 2,3-dihydro-1H-indolyl (including, for example, 2,3-dihydro-1H-indol-2-yl or 2,3-dihydro-1H-indol-5-yl, and the like), isoindolyl, indolinyl, isoindolinyl, benzimidazolyl, benzodioxol-4-yl, benzofuranyl, cinnolinyl, indolizinyl, naphthyridin-3-yl, phthalazin-3-yl, phthalazin-4-yl, pteridinyl, purinyl, quinazolinyl, quinoxalinyl, tetrazoyl, pyrazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, oxazolyl, isooxazolyl, oxadiazolyl, benzoxazolyl, quinolinyl, isoquinolinyl, tetrahydroisoquinolinyl (including, for example, tetrahydroisoquinolin-4-yl or tetrahydroisoquinolin-6-yl, and the like), pyrrolo[3,2-c]pyridinyl (including, for example, pyrrolo[3,2-c]pyridin-2-yl or pyrrolo[3,2-c]pyridin-7-yl, and the like), benzopyranyl, thiazolyl, isothiazolyl, thiadiazolyl, benzothiazolyl, benzothienyl, and the derivatives thereof, or N-oxide or a protected derivative thereof.

[0062] "Hetereoarylalkyl" means an alkyl group substituted with one or two heteroaryl groups as defined herein.

[0063] "Heterocycloalkyl" means a saturated or partially unsaturated monovalent monocyclic group of 3 to 8 ring atoms or a saturated or partially unsaturated monovalent fused bicyclic group of 5 to 12 ring atoms in which one or more, for example one, two, three, or four ring heteroatoms independently selected from -O-, -S(O)_n- (n is 0, 1, or 2), -N=, -N(R^y)- (where R^y is hydrogen, alkyl, hydroxy, alkoxy, acyl, or alkylsulfonyl), the remaining ring atoms being carbon. One or two ring carbon atoms may be replaced by a -C(O)-, -C(S)-, or -C(=NH)- group. Fused bicyclic radical includes bridged ring systems. Unless otherwise stated, the valency of the group may be located on any atom of any ring within the radical, valency rules permitting. In particular, when the point of valency is located on a nitrogen atom, R^y is absent. In another embodiment the term heterocycloalkyl includes, but is not limited to, azetidinyl, pyrrolidinyl, 2-oxopyrrolidinyl, 2,5-dihydro-1H-pyrrolyl, piperidinyl, 4-piperidonyl, morpholinyl, piperazinyl, 2-oxopiperazinyl, tetrahydropyranyl, 2-oxopiperidinyl, thiomorpholinyl, thiamorpholinyl, perhydroazepinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, dihydropyridinyl, tetrahydropyridinyl, oxazolinyl, oxazolidinyl, isoxazolidinyl, thiazolinyl, thiazolidinyl, quinuclidinyl, isothiazolidinyl, octahydroindolyl, octahydroisoindolyl, decahydroisoquinolyl, tetrahydrofuryl, and tetrahydropyranyl, and the derivatives thereof and N-oxide or a protected derivative thereof.

[0064] "Heterocycloalkylalkyl" means an alkyl group, as defined herein, substituted with one or two heterocycloalkyl groups, as defined herein.

[0065] "Hydroxyalkyl" means an alkyl radical, as defined herein, substituted with at least one, for example one, two, or three, hydroxy groups, provided that if two hydroxy groups are present they are not both on the same carbon atom. Representative examples include, but are not limited to, hydroxymethyl, 2-hydroxyethyl, 2-hydroxypropyl, 3-hydroxypropyl, 1-(hydroxymethyl)-2-methylpropyl, 2-hydroxybutyl, 3-hydroxybutyl, 4-hydroxybutyl, 2,3-dihydroxypropyl, 1-(hydroxymethyl)-2-hydroxyethyl, 2,3-dihydroxybutyl, 3,4-dihydroxybutyl and 2-(hydroxymethyl)-3-hydroxypropyl, for example 2-hydroxyethyl, 2,3-dihydroxypropyl, or 1-(hydroxymethyl)-2-hydroxyethyl, and the like.

[0066] "Hydroxyamino" means a -NH(OH) group.

[0067] "Optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances in which it does not. One of ordinary skill in the art would understand that with respect to any molecule described as containing one or more optional substituents, only sterically practical and/or synthetically feasible compounds are meant to be included. "Optionally substituted " refers to all subsequent modifiers in a term. So, for example, in the term "optionally substituted arylC_1-8 alkyl," both the "C_1-8 alkyl" portion and the "aryl" portion of the molecule may or may not be substituted. A list of exemplary optional substitutions is presented below in the definition of "substituted."

[0068] "Optionally substituted alkyl" means an alkyl radical, as defined herein, optionally substituted with one or more groups, for example one, two, three, four, or five groups, independently selected from alkylcarbonyl, alkenylcarbonyl, cycloalkylcarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, amino, alkylamino, dialkylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cyano, cyanoalkylaminocarbonyl, alkoxy, alkenyloxy, hydroxy, hydroxyalkoxy, carboxy, alkylcarbonylamino, alkylcarbonyloxy, alkylS(O)_0-2-, alkenyl-S(O)_0-2-, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, alkylsulfonyl-NR^c- (where R^c is hydrogen, alkyl, optionally substituted alkenyl, optionally substituted alkynyl, hydroxy, alkoxy, alkenyloxy, or cyanoalkyl), alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylaminoalkyloxy, dialkylaminoalkyloxy, alkoxycarbonyl, alkenyloxycarbonyl, alkoxycarbonylamino, alkylaminocarbonylamino, dialkylaminocarbonylamino, alkoxyalkyloxy, and -C(O)NR^aR^b (where R^a and R^b are independently hydrogen, alkyl, optionally substituted alkenyl, optionally substituted alkynyl, hydroxy, alkoxy, alkenyloxy, or cyanoalkyl).

[0069] "Optionally substituted alkenyl" means an alkenyl radical, as defined herein, optionally substituted with one or more groups, for example one, two, or three groups, independently selected from alkylcarbonyl, alkenylcarbonyl, cycloalkylcarbonyl, alkylcarbonyloxy, alkenylcarbonyloxy, amino, alkylamino, dialkylamino, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, cyano, cyanoalkylaminocarbonyl, alkoxy, alkenyloxy, hydroxy, hydroxyalkoxy, carboxy, alkylcarbonylamino, alkylcarbonyloxy, alkyl-S(O)_0-2-, alkenyl-S(O)_0-2-, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, alkylsulfonyl-NR^c- (where R^c is hydrogen, optionally substituted alkyl, optionally substituted alkynyl, hydroxy, alkoxy, or alkenyloxy), alkylaminocarbonyloxy, dialkylaminocarbonyloxy, alkylaminoalkyloxy, dialkylaminoalkyloxy, alkoxycarbonyl, alkenyloxycarbonyl, alkoxycarbonylamino, alkylaminocarbonylamino, dialkylaminocarbonylamino, alkoxyalkyloxy, and -C(O)NR^aR^b (where R^a and R^b are independently hydrogen, optionally substituted alkyl, alkenyl, optionally substituted alkynyl, hydroxy, alkoxy, or alkenyloxy).

[0070] "Optionally substituted aryl" means an aryl group, as defined herein, which is optionally substituted with one, two, three, four, of five groups selected from halo, haloalkyl, haloalkoxy, hydroxy, lower alkyl, lower alkenyl, lower alkynyl, alkoxy, carboxy, carboxy ester, amino, alkylamino, dialkylamino, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, -C(O)NR'R" (where R' is hydrogen or alkyl and R" is hydrogen, alkyl, aryl, heteroaryl, or
heterocycloalkyl), -NR'C(O)R" (where R' is hydrogen or alkyl and R" is alkyl, aryl, heteroaryl, or heterocycloalkyl), and -NHS(O)₂R' (where R' is alkyl, aryl, or heteroaryl).

[0071] "Optionally substituted heteroaryl" means a heteroaryl group, as defined herein, optionally substituted with one, two, three, four, or five groups selected from halo, haloalkyl, haloalkoxy, lower alkyl, lower alkenyl, lower alkynyl, alkoxy, hydroxy, oxo (valency rules permitting), carboxy, carboxy ester, amino, alkylamino, dialkylamino, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, heteroaryl, optionally substituted aryl, -C(O)NR'R" (where R' is hydrogen or alkyl and R" is hydrogen, alkyl, aryl, heteroaryl, or heterocycloalkyl), -NR'C(O)R" (where R' is hydrogen or alkyl and R" is alkyl, aryl, heteroaryl, or heterocycloalkyl), and -NHS(O)₂R' (where R' is alkyl, aryl, or heteroaryl).

[0072] "Optionally substituted heterocycloalkyl" means a heterocycloalkyl, as defined herein, optionally substituted with one, two, three, four, or five groups selected from halo, haloalkyl, haloalkoxy, hydroxy, oxo, lower alkyl, lower alkenyl, lower alkynyl, alkoxy, optionally substituted cycloalkyl, heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, alkylaminoalkyl, dialkylaminoalkyl, carboxy, carboxy ester, -C(O)NR'R" (where R' is hydrogen or alkyl and R" is hydrogen, alkyl, aryl, heteroaryl, or heterocycloalkyl), -NR'C(O)R" (where R' is hydrogen or alkyl and R" is alkyl, aryl, heteroaryl, or heterocycloalkyl), amino, alkylamino, dialkylamino, and -NHS(O)₂R' (where R' is alkyl, aryl, or heteroaryl).

[0073] "Saturated bridged ring system" refers to a bicyclic or polycyclic ring system that is not aromatic. Such a system may contain isolated or conjugated unsaturation, but not aromatic or heteroaromatic rings in its core structure (but may have aromatic substitution thereon). For example, hexahydro-furo[3,2-b]furan, 2,3,3a,4,7,7a-hexahydro-1H-indene, 7-aza-bicyclo[2.2.1]heptane, and 1,2,3,4,4a,5,8,8a-octahydro-naphthalene are all included in the class "saturated bridged ring system."

[0074] "Spirocyclyl" or "spirocyclic ring" refers to a ring originating from a particular annular carbon of another ring. For example, as depicted below, a ring atom of a saturated bridged ring system (rings C and C'), but not a bridgehead atom, can be a shared atom between the saturated bridged ring system and a spirocyclyl (ring D) attached thereto. A spirocyclyl can be carbocyclic or heteroalicyclic.

[0075] "Yield" for each of the reactions described herein is expressed as a percentage of the theoretical yield.

Definitions for the Compound of formula 100

[0076] The terms used to describe the scope of formula 100 are defined in WO 2004/006846 (US Nat'l Stage Application Serial No. 10/522,004) which is herein incorporated by reference. For example "optionally substituted alkyl" for formula 100 has the meaning given in WO 2004/006846 (US Nat'l Stage Application Serial No. 10/522,004). Whenever a compound of formula 100 is described in this application, whether by structure or by use of the term "formula 100," the terms used to describe that compound are defined by WO 2004/006846 (US Nat'l Stage Application Serial No. 10/522,004).

Other Definitions

[0077] "AKT inhibitor" includes, for example, LY294002, PKC 412, perifosine, compounds in Table 2a, compounds in Table 2b, and compounds described in WO 2006/071819 and WO05/117909. These references also describe in vitro assays that can be used to determine the inhibitory activity of AKT.

[0078] "Alkylating agent" includes, for example, one or more of the following: Chlorambucil, Chlormethine, Cyclophosphamide, Ifosfamide, Melphalan, Carmustine, Streptozocin, Fotemustine, Lomustine, Streptozocin, Carboplatin, Cisplatin, Oxaliplatin, BBR3464, Busulfan, Dacarbazine, Mechlorethamine, Procarbazine, Temozolomide, ThioTEPA, and Uramustine.

[0079] "Antibody" includes, for example, one or more of the following: an IGF1R antibody (including, for example, αIGF-1R A12 MoAb, 19D12, h7C10 and CP-751871), an EGFR antibody (including, for example, Cetuximab (Erbitux®) and Panitumumab), an ErbB2 antibody (including, for example, Trastuzumab (Herceptin®)), a VEGF antibody (including, for example, Bevacizumab (Avastin®)), an IgG1 antibody (including, for example, Ibritumomab (tiuxetan)), a CD20 antibody (including, for example, Rituximab and Tositumomab), a CD33 antibody (including, for example, Gemtuzumab and Gemtuzumab ozogamicin), and a CD52 antibody (including, for example, Alemtuzumab).

[0080] "Antimetabolite" include, for example, methotrexate, Pemetrexed, Raltitrexed, Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Thioguanine, Capecitabine, Cytarabine, fluorouracil (administered with or without leucovorin or folinic acid), and Gemcitabine.

[0081] "Antimicrotubule agent" includes, for example, Vincristine,Vinblastine, Vinorelbine, Vinflunine, and Vindesine.

[0082] "Aromatase inhibitor" includes, for example, one or more of the following: Aminoglutethimide, Anastrozole (Arimidex®), Letrozole (Femara®), Exemestane (Aromasin®), and Formestane (Lentaron®).

[0083] "Cancer" refers to cellular-proliferative disease states, including but not limited to: Cardiac: sarcoma (angiosarcoma, fibrosarcoma, rhabdomyosarcoma, liposarcoma), myxoma, rhabdomyoma, fibroma, lipoma and teratoma; Lung: bronchogenic carcinoma (squamous cell, undifferentiated small cell, undifferentiated large cell, adenocarcinoma), alveolar (bronchiolar) carcinoma, bronchial adenoma, sarcoma, lymphoma, chondromatous hanlartoma, inesothelioma; Gastrointestinal: esophagus (squamous cell carcinoma, adenocarcinoma, leiomyosarcoma, lymphoma), stomach (carcinoma, lymphoma, leiomyosarcoma), pancreas (ductal adenocarcinoma, insulinoma, glucagonoma, gastrinoma, carcinoid tumors, vipoma), small bowel (adenocarcinoma, lymphoma, carcinoid tumors, Karposi's sarcoma, leiomyoma, hemangioma, lipoma, neurofibroma, fibroma), large bowel (adenocarcinoma, tubular adenoma, villous adenoma, hamartoma, leiomyoma); Genitourinary tract: kidney (adenocarcinoma, Wilm's tumor [nephroblastoma], lymphoma, leukemia), bladder and urethra (squamous cell carcinoma, transitional cell carcinoma, adenocarcinoma), prostate (adenocarcinoma, sarcoma), testis (seminoma, teratoma, embryonal carcinoma, teratocarcinoma, choriocarcinoma, sarcoma, interstitial cell carcinoma, fibroma, fibroadenoma, adenomatoid tumors, lipoma); Liver: hepatoma (hepatocellular carcinoma), cholangiocarcinoma, hepatoblastoma, angiosarcoma, hepatocellular adenoma, hemangioma; Bone: osteogenic sarcoma (osteosarcoma), fibrosarcoma, malignant fibrous histiocytoma, chondrosarcoma, Ewing's sarcoma, malignant lymphoma (reticulum cell sarcoma), multiple myeloma, malignant giant cell tumor chordoma, osteochronfroma (osteocartilaginous exostoses), benign chondroma, chondroblastoma, chondromyxofibroma, osteoid osteoma and giant cell tumors; Nervous system: skull (osteoma, hemangioma, granuloma, xanthoma, osteitis defornians), meninges (meningioma, meningiosarcoma, gliomatosis), brain (astrocytoma, medulloblastoma, glioma, ependymoma, germinoma [pinealoma], glioblastorna multiform, oligodendroglioma, schwannoma, retinoblastoma, congenital tumors), spinal cord neurofibroma, meningioma, glioma, sarcoma); Gynecological: uterus (endometrial carcinoma), cervix (cervical carcinoma, pre-tumor cervical dysplasia), ovaries (ovarian carcinoma [serous cystadenocarcinoma, mucinous cystadenocarcinoma, unclassified carcinoma], granulosa-thecal cell tumors, Sertoli-Leydig cell tumors, dysgerminoma, malignant teratoma), vulva (squamous cell carcinoma, intraepithelial carcinoma, adenocarcinoma, fibrosarcoma, melanoma), vagina (clear cell carcinoma, squamous cell carcinoma, botryoid sarcoma (embryonal rhabdomyosarcoma], fallopian tubes (carcinoma); Hematologic: blood (myeloid leukemia [acute and chronic], acute lymphoblastic leukemia, chronic lymphocytic leukemia, myeloproliferative diseases, multiple myeloma, myelodysplastic syndrome), Hodgkin's disease, non-Hodgkin's lymphoma [malignant lymphoma]; Skin: malignant melanoma, basal cell carcinoma, squamous cell carcinoma, Karposi's sarcoma, moles dysplastic nevi, lipoma, angioma, dermatofibroma, keloids, psoriasis; Adrenal Glands: neuroblastoma; and breast cancer. Thus, the term "cancerous cell" as provided herein, includes a cell afflicted by any one of the above-identified conditions.

[0084] "Chemotherapeutic agent" includes, but is not limited to, an AKT inhibitor, an alkylating agent, an antimetabolite, an antimicrotubule agent, an aromatase inhibitor, a c-KIT inhibitor, a cMET inhibitor, an EGFR inhibitor, an ErbB2 inhibitor, a Flt-3 inhibitor, an HSP90 inhibitor, an IGF1R inhibitor, a platin, a Raf inhibitor, rapamycin, a Rapamycin analogue, a Receptor Tyrosine Kinase inhibitor, a taxane, a topoisomerase inhibitor, a SRC and/or ABL kinase inhibitor, and a VEGFR inhibitor. A pharmaceutically acceptable salt, solvate, and/or hydrate of a chemotherapeutic agent can be prepared by one of ordinary skill in the art and such salt, solvate, and/or hydrates thereof can be used to practice the invention.

[0085] "c-KIT inhibitor" includes, for example, imatinib, sunitinib, nilotinib, AMG 706, sorafenib, compounds in Table 3b, compounds in Table 3c, compounds in Table 8, compounds in Table 9, and compounds described in WO 2006/108059, WO/2005/020921, WO/2006/033943, and WO 2005/030140.

[0086] "cMET inhibitor" includes, for example, compounds in Table 3a, compounds in Table 3b, compounds in Table 3c, compounds described in WO06/108059, WO 2006/014325, and WO 2005/030140.

[0087] "EGFR inhibitor"includes, for example, one or more of the following: pelitinib, lapatinib (Tykerb®), gefitinib (Iressa®), erlotinib (Tarceva®), Zactima (ZD6474, vandetinib), AEE788 and HKI-272, EKB-569, CI-1033, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, compounds in Table 4, compounds in Table 7, and compounds described in WO 2004/006846 and WO 2004/050681.

[0088] "ErbB2 inhibitor" includes, for example, lapatinib (GW572016), PKI-166, canertinib, CI-1033, HKI272, and EKB-569.

[0089] "Flt-3 inhibitor" includes, for example, CEP-701, PKC 412, MLN518, sunitinib, sorafenib, compounds in Table 3a, compounds in Table 3b, compounds in Table 3c, compounds in Table 9, and compounds described in WO 2006/108059, WO/2006/033943, WO 2006/014325, and WO 2005/030140.

[0090] "Hormone therapy" or "hormonal therapy" includes, for example, treatment with one or more of the following: steroids (e.g. dexamethasone), finasteride, tamoxifen, and an aromatase inhibitor.

[0091] "HSP90 inhibitor" includes, for example, 17-AAG, 17-DMAG, Geldanamycin, 5-(2,4-dihydroxy-5-isopropylphenyl)-N-ethyl-4-(4-(morpholinomethyl)phenyl)isoxazole-3-carboxamide [NVP-AUY922 (VER 52296)], 6-chloro-9-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-9H-purin-2-amine (CNF2024, also named BIIB021), compounds disclosed in WO2004072051 (which is herein incorporated by reference), compounds disclosed in WO2005028434 (which is herein incorporated by reference), compounds disclosed in WO2007035620 (which is herein incorporated by reference) and compounds disclosed in WO2006091963 (which is herein incorporated by reference).

[0092] "IGF1R inhibitor" includes, for example, Tyrphostin AG 1024, compounds in Table 5a, compounds in Table 5b, and compounds described in WO06/074057.

[0093] "Kinase-dependent diseases or conditions" refer to pathologic conditions that depend on the activity of one or more lipid kinases. Kinases either directly or indirectly participate in the signal transduction pathways of a variety of cellular activities including proliferation, adhesion, migration, differentiation and invasion. Diseases associated with kinase activities include tumor growth, the pathologic neovascularization that supports solid tumor growth, and associated with other diseases where excessive local vascularization is involved such as ocular diseases (diabetic retinopathy, age-related macular degeneration, and the like) and inflammation (psoriasis, rheumatoid arthritis, and the like).

[0094] While not wishing to be bound to theory, phosphatases can also play a role in "kinase-dependent diseases or conditions" as cognates of kinases; that is, kinases phosphorylate and phosphatases dephosphorylate, for example lipid substrates. Therefore compounds of the invention, while modulating kinase activity as described herein, may also modulate, either directly or indirectly, phosphatase activity. This additional modulation, if present, may be synergistic (or not) to activity of compounds of the invention toward a related or otherwise interdependent kinase or kinase family. In any case, as stated previously, the compounds of the invention are useful for treating diseases characterized in part by abnormal levels of cell proliferation (i.e. tumor growth), programmed cell death (apoptosis), cell migration and invasion and angiogenesis associated with tumor growth.

[0095] "Metabolite" refers to the break-down or end product of a compound or its salt produced by metabolism or biotransformation in the animal or human body; for example, biotransformation to a more polar molecule such as by oxidation, reduction, or hydrolysis, or to a conjugate (see Goodman and Gilman, "The Pharmacological Basis of Therapeutics" 8.sup.th Ed., Pergamon Press, Gilman et al. (eds), 1990 for a discussion of biotransformation). As used herein, the metabolite of a compound of the invention or its salt may be the biologically active form of the compound in the body. In one example, a prodrug may be used such that the biologically active form, a metabolite, is released in vivo. In another example, a biologically active metabolite is discovered serendipitously, that is, no prodrug design per se was undertaken. An assay for activity of a metabolite of a compound of the present invention is known to one of skill in the art in light of the present disclosure.

[0096] "Patient" for the purposes of the present invention includes humans and other animals, particularly mammals, and other organisms. Thus the methods are applicable to both human therapy and veterinary applications. In another embodiment the patient is a mammal, and in another embodiment the patient is human.

[0097] A "pharmaceutically acceptable salt" of a compound means a salt that is pharmaceutically acceptable and that possesses the desired pharmacological activity of the parent compound. It is understood that the pharmaceutically acceptable salts are non-toxic. Additional information on suitable pharmaceutically acceptable salts can be found in Remington's Pharmaceutical Sciences, 17th ed., Mack Publishing Company, Easton, PA, 1985, which is incorporated herein by reference or S. M. Berge, et al., "Pharmaceutical Salts," J. Pharm. Sci., 1977;66:1-19 both of which are incorporated herein by reference.

[0098] Examples of pharmaceutically acceptable acid addition salts include those formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like; as well as organic acids such as acetic acid, trifluoroacetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, 3-(4-hydroxybenzoyl)benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, glucoheptonic acid, 4,4'-methylenebis-(3-hydroxy-2-ene-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, p-toluenesulfonic acid, and salicylic acid and the like.

[0099] Examples of a pharmaceutically acceptable base addition salts include those formed when an acidic proton present in the parent compound is replaced by a metal ion, such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Preferable salts are the ammonium, potassium, sodium, calcium, and magnesium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include, but are not limited to, salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins. Examples of organic bases include isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, tromethamine, N-methylglucamine, polyamine resins, and the like. Exemplary organic bases are isopropylamine, diethylamine, ethanolamine, trimethylamine, dicyclohexylamine, choline, and caffeine.

[0100] "Platin," and "platin-containing agent" include, for example, cisplatin, carboplatin, and oxaliplatin.

[0101] "Prodrug" refers to compounds that are transformed (typically rapidly) in vivo to yield the parent compound of the above formulae, for example, by hydrolysis in blood. Common examples include, but are not limited to, ester and amide forms of a compound having an active form bearing a carboxylic acid moiety. Examples of pharmaceutically acceptable esters of the compounds of this invention include, but are not limited to, alkyl esters (for example with between about one and about six carbons) the alkyl group is a straight or branched chain. Acceptable esters also include cycloalkyl esters and arylalkyl esters such as, but not limited to benzyl. Examples of pharmaceutically acceptable amides of the compounds of this invention include, but are not limited to, primary amides, and secondary and tertiary alkyl amides (for example with between about one and about six carbons). Amides and esters of the compounds of the present invention may be prepared according to conventional methods. A thorough discussion of prodrugs is provided in T. Higuchi and V. Stella, "Pro-drugs as Novel Delivery Systems," Vol 14 of the A.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987, both of which are incorporated herein by reference for all purposes.

[0102] "Raf inhibitor" includes, for example, sorafenib, RAF 265 (CHIR 265), compounds in Table 6, and compounds described in WO 2005/112932. These references also describe in vitro assays that can be used to determine the inhibitory activity of RAF.

[0103] "Rapamycin analogue" includes for example, CCI-779, AP23573, RAD 001, TAFA 93, and compounds described in WO 2004/101583 and US 7,160,867 which are each incorporated herein by reference in their entireties.

[0104] "Receptor Tyrosine Kinase inhibitor" includes, for example, inhibitors of AKT, EGFR, ErbB2, IGF1R, KIT, Met, Raf, and VEGFR2. Examples of receptor tyrosine kinase inhibitors can be found in WO 2006/108059 (US Nat'l Stage Application Serial No. 11/910,720), WO 2006/074057 (US Nat'l Stage Application Serial No. 11/722,719), WO 2006/071819 (US Nat'l Stage Application Serial No. 11/722,291), WO 2006/014325 (US Nat'l Stage Application Serial No. 11/571,140), WO 2005/117909 (US Nat'l Stage Application Serial No. 11/568,173), WO 2005/030140 (US Nat'l Stage Application Serial No. 10/573,336), WO 2004/050681 US Nat'l Stage Application Serial No. 10/533,555), WO 2005/112932 (US Nat'l Stage Application Serial No. 11/568,789), and WO 2004/006846 (US Nat'l Stage Application Serial No. 10/522,004), each of which is incorporated herein by reference for all purposes. In particular, the applications cited in this paragraph are incorporated for the purpose of providing specific examples and generic embodiments (and the definitions associated with the terms used in the embodiments) of compounds that are useful in the practice of the invention. These references also describe in vitro assays useful in the practice of this invention.

[0105] "Taxane" includes, for example, one or more of the following: Paclitaxel (Taxol^®) and Docetaxel (Taxotere^®).

[0106] "Therapeutically effective amount" is an amount of a compound of the invention, that when administered to a patient, ameliorates a symptom of the disease. The amount of a compound of the invention which constitutes a "therapeutically effective amount" will vary depending on the compound, the disease state and its severity, the age of the patient to be treated, and the like. The therapeutically effective amount can be determined routinely by one of ordinary skill in the art having regard to their knowledge and to this disclosure.

[0107] "Topoisomerase inhibitor" includes, for example, one or more of the following: amsacrine, camptothecin, etoposide, etoposide phosphate, exatecan, irinotecan, lurtotecan, and teniposide, and topotecan.

[0108] "Treating" or "treatment" of a disease, disorder, or syndrome, as used herein, includes (i) preventing the disease, disorder, or syndrome from occurring in a human, i.e. causing the clinical symptoms of the disease, disorder, or syndrome not to develop in an animal that may be exposed to or predisposed to the disease, disorder, or syndrome but does not yet experience or display symptoms of the disease, disorder, or syndrome; (ii) inhibiting the disease, disorder, or syndrome, i.e., arresting its development; and (iii) relieving the disease, disorder, or syndrome, i.e., causing regression of the disease, disorder, or syndrome. As is known in the art, adjustments for systemic versus localized delivery, age, body weight, general health, sex, diet, time of administration, drug interaction and the severity of the condition may be necessary, and will be ascertainable with routine experimentation by one of ordinary skill in the art.

[0109] "SRC and/or ABL kinase inhibitor" includes, for example, dasatinib, imatinib (Gleevec®), and compounds described in WO 2006/074057.

[0110] "VEGFR inhibitor" includes, for example, one or more of the following: VEGF Trap, ZD6474 (vandetanib, Zactima), sorafenib, Angiozyme, AZD2171 (cediranib), pazopanib, sorafenib, axitinib, SU5416 (semaxanib), PTK787 (vatalanib), AEE778, RAF 265, sunitinib (Sutent), N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, compounds in Table 7, and compounds described in WO 2004/050681 and WO 2004/006846 .

[0111] The following paragraphs present a number of options for compounds described herein. In each instance, the option includes both the recited compounds as well as individual isomers and mixtures of isomers. In addtion, in each instance, the option optionally includes the pharmaceutically acceptable salts, hydrates, and/or solvates of the recited compounds and any individual isomers or mixture of isomers thereof.

[0112] For each of the following options, the Compound of Formula I can, for example, be of Formula I(a) or be selected from a Compound in Table 1.

[0113] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, where growth and/or survival of tumor cells of the cancer is enhanced, at least in part, by the activity of PI3K; in combination with one or more treatments selected from surgery, one or more chemotherapeutic agents, one or more hormone therapies, one or more antibodies, one or more immunotherapies radioactive iodine therapy, and radiation.

[0114] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery, one or more chemotherapeutic agents, one or more hormone therapies, one or more antibodies, one or more immunotherapies, radioactive iodine therapy, and radiation; where the cancer is selected from breast cancer, colon cancer, rectal cancer, endometrial cancer, gastric carcinoma (including gastrointestinal carcinoid tumors and gastrointestinal stromal tumors), glioblastoma, hepatocellular carcinoma, small cell lung cancer, non-small cell lung cancer (NSCLC), melanoma, ovarian cancer, cervical cancer, pancreatic cancer, prostate carcinoma, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), non-Hodgkin's lymphoma, and thyroid carcinoma. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery, one or more chemotherapeutic agents, one or more hormone therapies, one or more antibodies, one or more immunotherapies, radioactive iodine therapy, and radiation; where the cancer is selected from prostate cancer, NSCLC, ovarian cancer, cervical cancer, breast cancer, colon cancer, rectal cancer, and glioblastoma. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery, one or more chemotherapeutic agents, one or more hormone therapies, one or more antibodies, one or more immunotherapies, radioactive iodine therapy, and radiation; where the cancer is selected from NSCLC, breast cancer, prostate cancer, glioblastoma, and ovarian cancer.

[0115] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or more chemotherapeutic agents.

[0116] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents independently selected from rapamycin, a rapamycin analogue, an alkylating agent, a taxane, a platin, an EGFR inhibitor, and an ErbB2 inhibitor. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above,
in combination with a treatment where the treatment is one or two chemotherapeutic agents independently selected from rapamycin, temozolomide, paclitaxel, docetaxel, carboplatin, cisplatin, oxaliplatin, gefitinib (Iressa®), erlotinib (Tarceva®), Zactima (ZD6474), HKI-272, pelitinib, canertinib, a compound selected from Table 4, a compound in Table 7, and lapatinib. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents independently selected from rapamycin, temozolomide, paclitaxel, docetaxel, carboplatin, trastuzumab, erlotinib, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, a compound in Table 7, and lapatinib. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the defined combination a treatment treatment is one or two chemotherapeutic agents independently selected from rapamycin, paclitaxel, carboplatin, erlotinib, and N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine.

[0117] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents independently selected from a platin and a taxane. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents independently selected from carboplatin, cisplatin, oxaliplatin, and paclitaxel.

[0118] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an AKT inhibitor. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an AKT inhibitor selected from perifosine, PKC 412, a compound in Table 2a, and a compound in Table 2b.

[0119] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a cMET inhibitor. Also described is the use in a method bf treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a cMET inhibitor selected from a compound in Table 3a, a compound in Table 3b, and a compound in Table 3c.

[0120] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an EGFR inhibitor. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above,
in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an EGFR inhibitor selected from lapatinib (Tykerb®), gefitinib (Iressa®), erlotinib (Tarceva®), Zactima (ZD6474), AEE788, HKI-272, EKB-569, CI 1033, a compound selected from Table 4, and a compound in Table 7. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an EGFR inhibitor selected from lapatinib (Tykerb®), gefitinib (Iressa®), erlotinib (Tarceva®), Zactima (ZD6474), AEE788, HKI-272, EKB-569, CI 1033, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine N-(4-bromo-3-chloro-2-fluorophenyl)-7-({(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, and N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine.

[0121] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an ErbB2 inhibitor. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an ErbB2 inhibitor selected from lapatinib, EKB-569, HKI272, CI 1033, PKI-166, and a compound selected from Table 4.

[0122] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an HSP90 inhibitor. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an HSP90 inhibitor selected from 17-AAG, 17-DMAG, Geldanamycin, and CNF2024. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an HSP90 inhibitor selected from 17-AAG, 17-DMAG, and Geldanamycin.

[0123] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an IGF1R inhibitor. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is an IGF1R inhibitor selected from Table 5a and Table 5b.

[0124] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a Raf inhibitor. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a Raf inhibitor selected from sorafenib, RAF 265 (CHIR-265), and a compound in Table 6.

[0125] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount ofa Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a VEGFR inhibitor. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a VEGFR inhibitor selected from VEGF Trap, ZD6474 (Zactima), cediranib (AZ2171), pazopanib, sunitinib, sorafenib, axitinib, AEE788, RAF 265 (CHIR-265), a compound selected from Table 4, and a compound selected from Table 7.

[0126] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a cKIT inhibitor. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a cKIT inhibitor selected from imatinib, sunitinib, nilotinib, AMG 706, sorafenib, a compound in Table 3b, a compound in Table 3c, a compound in Table 8, and a compound in Table 9.

[0127] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a FLT3 inhibitor. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above,
in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is a FLT3 inhibitor selected from CEP-701, PKC 412, sunitinib, MLN518, sunitinib, sorafenib, a compound in Table 3a, a compound in Table 3b, a compound in Table 3c, and a compound in Table 9.

[0128] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula 1, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from rapamycin, a rapamycin analogue, PI103, and SF 1126. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is select from rapamycin, CCI-779, AP23573, RAD 001, TAFA 93, PI103, and SF 1126. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is rapamycin.

[0129] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is of formula 100:

where q is 1, 2, or 3; E is -NR⁹-, -O-, or absent and Y is -CH₂CH₂-, -CH₂-, or absent provided that when E is -NR⁹- or -O-, then Y is -CH₂CH₂-; R² is selected from halogen, trihalomethyl, -CN, -NO₂, -OR³, and lower alkyl; R⁸ is selected from -H, lower alkyl, -C(O)OR³, -C(O)N(R³)R⁴, -SO₂R⁴, and -C(O)R³; R⁹ is hydrogen or lower alkyl; R³ is hydrogen or R⁴; R⁴ is selected from lower alkyl, aryl, lower arylalkyl, heterocyclyl, and lower heterocyclylalkyl; or R³ and R⁴, when taken together with a common nitrogen to which they are attached, form a five- to seven-membered heterocyclyl, said five- to seven-membered heterocyclyl optionally containing one or more additional heteroatom selected from N, O, S, and P; or a single geometric isomer, stereoisomer, racemate, enantiomer, or diastereomer, thereof and optionally as a pharmaceutically acceptable salt, additionally optionally as a solvate, and additionally as a hydrate thereof. The terms used to describe the scope of formula 100 are defined in WO 2004/006846 (US Nat'l Stage Application Serial No. 10/522,004) which is herein incorporated by reference. Whenever a compound of formula 100 is described in this application, whether by structure or by use of the term "formula 100," the terms used to describe that compound are defined by WO 2004/006846 (US Nat'l Stage Application Serial No. 10/522,004). In particular, "alkyl" in formula 100 is intended to include linear, branched, or cyclic hydrocarbon structures and combinations thereof, inclusively; "lower alkyl" means alkyl groups of from one to six carbon atoms. "Aryl" in formula 100 means an aromatic six- to fourteen-membered carbocyclic rings which include, for example, benzene, naphthalene, indane, tetralin, fluorene and the like. "Lower arylalkyl" in formula 100 means a residue in which an aryl moiety is attached to a parent structure via one of an alkylene, alkenylene, or alkynylene radical where the "alkyl" portion of the group has one to six carbons; examples include benzyl, phenethyl, phenylvinyl, phenylallyl and the like. In formula 100, "heterocyclyl" means a stable monocyclic, bicyclic or tricyclic three- to fifteen-membered ring radical (including fused or bridged ring systems) that consists of carbon atoms and from one to five heteroatoms selected from the group consisting of nitrogen, phosphorus, oxygen and sulfur where the nitrogen, phosphorus, carbon and sulfur atoms in the heterocyclyl radical may be optionally oxidized to various oxidation states and the nitrogen atom may be optionally quaternized; and the ring radical may be partially or fully saturated or aromatic. "Lower heterocyclylalkyl" means a residue in which a heterocyclyl is attached to a parent structure via one of an alkylene, alkenylene, and alkynylene radical having one to six carbons.

[0130] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 2a. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 2a. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 2a.

[0131] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 2b. Also described is the use in a method bf treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 2b. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 2b.

[0132] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined in the Summary of the Invention, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3a. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3a. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3a.

[0133] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3b. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3b. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected m a compound in Table 3b.

[0134] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3c. Also described is the use in a method bf treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3c. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 3c.

[0135] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 4. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 4. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 4.

[0136] Also described is the use in a method'of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}-oxy)-6-(methyloxy)quinazolin-4-amine, or N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a) in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, or N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one
or two chemotherapeutic agents where one of the chemotherapeutic agents is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, or N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, optionally as a pharmaceutically acceptable salt and additionally optionnally as a hydrate and additionally optionally as a solvate thereof.

[0137] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof. Also described is a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a) in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table I in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionnally optionnally as a hydrate and additionally optionally as a solvate thereof.

[0138] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 5ac. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 5a. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 5a.

[0139] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 5b. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 5b. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 5b.

[0140] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 6. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 6. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selec from a compound in Table 6.

[0141] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 7. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 7. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 7.

[0142] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 8. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the e chemotherapeutic agents is selected from a compound in Table 8. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 8.

[0143] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 9. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a), in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 9. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1, in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agents is selected from a compound in Table 9.

[0144] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table I in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agent is paclitaxel.

[0145] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agent is rapamycin.

[0146] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table I in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agent is carboplatin.

[0147] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agent is erlotinib.

[0148] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table I in combination with a treatment where the treatment is one or two chemotherapeutic agents where one of the chemotherapeutic agent is lapatinib.

[0149] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two antibodies where one of the antibodies is trastuzumab.

[0150] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two antibodies where one of the antibodies is cetuximab.

[0151] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table I in combination with a treatment where the treatment is one or two antibodies where one of the antibodies is panitumumab.

[0152] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two antibodies where one of the antibodies is bevacizumab.

[0153] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is radiation. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a) in combination with a treatment where the treatment is radiation. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is radiation.

[0154] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two antibodies. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two antibodies independently selected from an IGF1R antibody (including, for example, ^αIGF-1R A 12 MoAb, ^αIGF-1R 19D12 MoAb, ^αIGF-1R h7C10 MoAb and ^αIGF-1R CP-751871 MoAb), Alemtuzumab, Bevacizumab (Avastin®), Gemtuzumab, Gemtuzumab ozogamicin, Ibritumomab tiuxetan, Panitumumab, Rituximab, Tositumomab, Omnitarg (pertuzimab), an anti-ErbB2 anibodys (including trastuzumab (Herceptin®)), and an anti-EGFR antibodies (including, for example, cetuximab (Erbitux), panitumumab, nimotuzumab, and EMD72000)).

[0155] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a) in combination with a treatment where the treatment is one or two antibodies. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a) in combination with a treatment where the treatment is one or two antibodies independently selected from an IGF1R antibody (including, for example, ^αIGF-1R A12 MoAb, ^αIGF-1R 19D12 MoAb, ^αIGF-1R h7C10 MoAb and ^αIGF-1R CP-751871 MoAb), Alemtuzumab, Bevacizumab (Avastin®), Gemtuzumab, Gemtuzumab ozogamicin, Ibritumomab tiuxetan, Panitumumab, Rituximab, Tositumomab, Omnitarg (pertuzimab), an anti-ErbB2 anibodys (including trastuzumab (Herceptin®)), and an anti-EGFR antibodies (including, for example, cetuximab (Erbitux), panitumumab, nimotuzumab, and EMD72000)).

[0156] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two antibodies. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table I in combination with a treatment where the treatment is one or two antibodies independently selected from an IGF1R antibody (including, for example, ^αIGF-1R A12 MoAb, ^αIGF-1R 19D12 MoAb, ^αIGF-1R h7C10 MoAb and ^αIGF-1R CP-751871 MoAb), Alemtuzumab, Bevacizumab (Avastin®), Gemtuzumab, Gemtuzumab ozogamicin, Ibritumomab tiuxetan, Panitumumab, Rituximab, Tositumomab, Omnitarg (pertuzimab), an anti-ErbB2 anibodys (including trastuzumab (Herceptin®)), and an anti-EGFR antibodies (including, for example, cetuximab (Erbitux), panitumumab, nimotuzumab, and EMD72000)).

[0157] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or more chemotherapeutic agents where one of the chemotherapeutic agent is temozolomide. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a) in combination with a treatment where the treatment is one or more chemotherapeutic agents where one of the chemotherapeutic agent is temozolomide. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or more chemotherapeutic agents where on of the chemotherapeutic agent is temozolomide.

[0158] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is surgery. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a) in combination with a treatment where the treatment is surgery. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table I in combination with a treatment where the treatment is surgery.

[0159] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where the treatment is one or two hormone therapies. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I or I(a), as defined above, in combination with a treatment where the treatment is one or two hormone therapies independently selected from tamoxifen, Toremifene (Fareston), Fulvestrant (Faslodex), Megestrol acetate (Megace), ovarian ablation, Raloxifene, a luteinizing hormone-releasing hormone (LHRH) analog (including goserelin and leuprolide), Megestrol acetate (Megace), and one or more aromatase inhibitors. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I or I(a), as defined above, in combination with a treatment where the treatment is one or two hormone therapies where one of the hormone therapies is an aromatase inhibitor selected from letrozole (Femara), anastrozole (Arimidex), and exemestane (Aromasin). Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I or I(a), as defined above, in combination with a treatment where the treatment is one or two hormone therapies independently selected from from tamoxifen and an aromatase inhibitor.

[0160] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where the treatment is one or two hormone therapies. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table I in combination with a treatment where one of the treatments is one or two hormone therapies independently selected from tamoxifen, Toremifene (Fareston), Fulvestrant (Faslodex), Megestrol acetate (Megace), ovarian ablation, Raloxifene, a luteinizing hormone-releasing hormone (LHRH) analog (including goserelin and leuprolide), Megestrol acetate (Megace), and one or two aromatase inhibitors. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where one of the treatments is one or two hormone therapies where one of the hormone therapies is an aromatase inhibitors selected from letrozole (Femara), anastrozole (Arimidex), and exemestane (Aromasin). Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where one of the treatments is one or two hormone therapies independently setected from from tamoxifen and an aromatase inhibitor.

[0161] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with a treatment where one of the treatments is one antibody selected from an EGFR antibody and an ErbB2 antibody, or the treatment is one or two chemotherapeutic agents independently selected from a rapamycin, rapamycin analogue, an alkylating agent, a taxane, a platin, an EGFR inhibitor, and an ErbB2 inhibitor. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I according to Formula I(a) in combination with a treatment where one of the treatments is one antibody selected from an EGFR antibody and an ErbB2 antibody, or the treatment is one or two chemotherapeutic agents independently selected from rapamycin, a rapamycin analogue, an alkylating agent, a taxane, a platin, an EGFR inhibitor, and an ErbB2 inhibitor. Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I selected from Table 1 in combination with a treatment where one of the treatments is one antibody selected from an EGFR antibody and an ErbB2 antibody, or the treatment is one or two chemotherapeutic agents independently selected from rapamycin, a rapamycin analogue, an alkylating agent, a taxane, a platin an EGFR inhibitor, and an ErbB2 inhibitor.

[0162] Also described is the use in a method of treating acute myelogenous leukemia (AML) which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from bone marrow or peripheral blood stem cell transplantation, radiation, one or two antibodies, and one or two chemotherapeutic agents. Also described is the use in a method of treating acute myelogenous leukemia (AML) which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or t treatments where one of the treatments is one antibody selected from Gemtuzumab ozogamicin (Mylotarg), ^αIGF-1R A12 MoAb, ^αIGF-1R 19D12 MoAb ^αIGF-1R h7C10 MoAb, ^αIGF-1R CP-751871 MoAb and trastuzumab. Also described is the use in a method of treating acute myelogenous leukemia (AML) which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents selected from Imatinib (i.e. Gleevec®), PKC 412, CEP-701, daunorubicin, doxorubicin, cytarabine (ara-C), an anthracycline drug such as daunorubicin or idarubicin (Daunomycin, Idamycin), 6-thioguanine, and a granulocyte colony-stimulating factor (such as Neupogen or Leukine).

[0163] Also described is the use in a method of treating chronic myelogenous leukemia (CML) which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from bone marrow or peripheral blood stem cell transplantation, radiation, one or two chemotherapeutic agents, immunotherapy, and one or two antibodies. Also described is the use in a method of treating chronic myelogenous leukemia (CML) which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two of the chemotherapeutic agents selected from Imatinib (i.e. Gleevec®), PKC 412, hydroxyurea (Hydrea), cytosine, cytosine arabinoside, dasatinib, AMN107, VX680 (MK0457), and cytarabine (ara-C). Also described is the use in a method of treating chronic myelogenous leukemia (CML) which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents selected from Imatinib (i.e. Gleevec®) and dasatinib. Also described is the use in a method of treating chronic myelogenous leukemia (CML) which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is immunotherapy and the immunotherapy is interferon therapy such as interferon-α.

[0164] Also described is the use in a method of treating prostate cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery (including cryosurgery), radiation, one or two chemotherapeutic agents, one or two antibodies, and one or two hormone therapies. Also described is the use in a method of treating prostate cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is an antibody selected from ^αIGF-1R A12 MoAb, ^αIGF-1R 19D12 MoAb, ^αIGF-1R h7C10 MoAb, and ^αIGF-1R CP-751871 MoAb. Also described is the use in a method of treating prostate cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two of the chemotherapeutic agents independently selected from rapamycin, mitoxantrone, prednisone, docetaxel (Taxotere), doxorubicin, etoposide, vinblastine, paclitaxel, and carboplatin. Also described is the use in a method of treating prostate cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two of the hormone therapy indepependently selected from androgen deprivation therapy and androgen suppression therapy. Also described is the use in a method of treating prostate cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or chemotherapeutic agents where one of the chemotherapeutic agents is a taxanes. Also described is the use in a method of treating prostate cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents where one of the chemotherapeutic agents is rapamycin.

[0165] Also described is the use in a method of treating melanoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery, radiation, one or two immunotherapies, one or two hormone therapies, and one or two chemotherapeutic agents. Also described is the use in a method of treating melanoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from an alkylating agent, a taxane, a platin, and a Raf inhibitor. Also described is the use in a method of treating melanoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from sorafenib, Paclitaxel (Taxol^®), Docetaxel (Taxotere^®), dacarbazine, rapamycin, imatinib mesylate (Gleevec®), sorafenib, cisplatin, carboplatin, dacarbazine (DTIC), carmustine (BCNU), vinblastine, temozolomide (Temodar), Melphalan, and imiquimod (Aldara). Also described is the use in a method of treating melanoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two immunotherapies independently selected from ipilimumab, interferon-alpha and interleukin-2. Also described is the use in a method of treating melanoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is hormone therapy where the hormone therapy is tamoxifen.

[0166] Also described is the use in a method of treating colon or rectal cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery, radiation, one or two antibodies, and one or two chemotherapeutic agents. Also described is the use in a method of treating colon or rectal cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is surgery selected from local excision, electrofulguration, segmental colon resection, polypectomy, local transanal resection, low anterior resection, abdominoperineal resection, and pelvic exenteration. Also described is the use in a method of treating colon or rectal cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from a platinum-containing compound (including cisplatin, oxaliplatin, and carboplatin), 5-fluorouracil (5-FU), leucovorin, capecitabine (Xeloda), irinotecan (Camptosar), FOLFOX (Folinic acid, 5-FU, Oxaliplatin), and leucovorin. Also described is the use in a method of treating colon or rectal cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two antibodies independently selected from cetuximab (Erbitux) and bevacizumab (Avastin).

[0167] Also described is the use in a method of treating pancreatic cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery, radiation, one or two antibodies, and one or two chemotherapeutic agents. Also described is the use in a method of treating pancreatic cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is selected from one or two chemotherapeutic agents independently selected from platinum-containing compound (including cisplatin, oxaliplatin, and carboplatin), 5-fluorouracil (5-FU), gemcitabine, a taxane (including paclitaxel and docetaxel), topotecan, irinotecan, capecitabine, streptozocin, erlotinib (Tarceva), , leucovorin, and capecitabine (Xeloda). Also described is the use in a method of treating pancreatic cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is an antibody wehre the antibody is cetuximab

[0168] Also described is the use in a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula 1, as defined above, in combination with one or more treatments independently selected from surgery, radiation, one or two chemotherapeutic agents, one or two hormone therapies, and one or two antibodies. Also described is the use in a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two of the chemotherapeutic agents independently selected from lapatinib (Tykerb^®), Paclitaxel (Taxol^®), docetaxel, capecitabine, Cyclophosphamide (Cytoxan), CMF (cyclophosphamide, fluoruracil, and methotrexate), methotrexate, fluorouracil, doxorubicin, epirubicin, gemcitabine, carboplatin (Paraplatin), cisplatin (Platinol), vinorelbine (Navelbine), capecitabine (Xeloda), pegylated liposomal doxorubicin (Doxil), albumin-bound paclitaxel (Abraxane), AC (adriamycin and Cyclophosphamide), adriamyclin, and pamidronate or zoledronic acid (to treat bone weakness). Also described is the use in a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two hormone therapies independently selected from tamoxifen, Toremifene (Fareston), Fulvestrant (Faslodex), Megestrol acetate (Megace), ovarian ablation, Raloxifene, a luteinizing hormone-releasing hormone (LHRH) analogs (including goserelin and leuprolide), Megestrol acetate (Megace), and one or more aromatase inhibitors. Also described is the use in a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two hormone therapies and one of the hormone therapies is an aromatase inhibitors selected from letrozole (Femara), anastrozole (Arimidex), and exemestane (Aromasin). Also described is the use in a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two antibodies independently selected from ^αIGF-1R A12 MoAb, ^αIGF-1R 19D12 MoAb, ^αIGF-1R h7C10 MoAb, ^αIGF-1R CP-751871 MoAb, bevacizumab (Avastin), and trastuzumab.

[0169] Also described is the use in a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents and one of the chemotherapeutic agents is erlotinib.

[0170] Also described is the use in a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two of the chemotherapeutic agents and one or two of the chemotherapeutic agents are independently selected from rapamycin, lapatinib, erlotinib, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof, and N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl} oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as hydrate and additionally optionally as a solvate thereof.

[0171] Also described is the use in a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two of the antibodies. Also described is the use in a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two antibodies and one of the antibodies is trastuzumab.

[0172] Also described is the use in a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two of the chemotherapeutic agents and one of the chemotherapeutic agents is selected from N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, and N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine; optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof

[0173] Also described is the use in a method of treating breast cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two of the chemotherapeutic agents and one of the chemotherapeutic agents is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof.

[0174] Also described is the use in a method of treating non-small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery, radiation, one or more antibodies, and one or more chemotherapeutic agents. Also described is the use in a method of treating non-small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from cisplatin, oxaliplatin, carboplatin, Zactima (ZD6474), Paclitaxel, Docetaxel (Taxotere®), Gemcitabine (Gemzar®), Vinorelbine, Irinotecan Etoposide, Vinblastine, Erlotinib (Tarceva®), gefitinib (Iressa), and Pemetrexed. Also described is the use in a method of treating non-small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is an antibody and the antibody is Bevacizumab. Also described is the use in a method of treating non-small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from cisplatin, oxaliplatin, carboplatin, Paclitaxel, Docetaxel (Taxotere®), and erlotinib (Tarceva®).

[0175] Also described is the use in a method of treating non-small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents and one of the chemotherapeutic agents is carboplatin.

[0176] Also described is the use in a method of treating non-small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents and one of the chemotherapeutic agents is selected from N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine, and N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine; optionally as a pharmaceutically acceptable salt and additionally optionnally as a hydrate and additionally optionally as a solvate thereof. Also described is the use in a method of treating non-small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents and one of the chemotherapeutic agents is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof.

[0177] Also described is the use in a method of treating small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery, radiation, and one or two chemotherapeutic agents. Also described is the use in a method of treating small cell lung cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapy agents independently selected from a platin (such as cisplatin, oxaliplatin, and carboplatin), gefitinib, vinorelbine, docetaxel, paclitaxel, etoposide, fosfamide, ifosfamide, cyclophosphamide, cyclophosphamide/doxorubicin/vincristine (CAV), doxorubicin, vincristine, gemcitabine, paclitaxel, vinorelbine, topotecan, irinotecan, methotrexate, and docetaxel.

[0178] Also described is the use in a method of treating papillary or anaplastic thyroid cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery, radiation, radioactive iodine therapy, one or two hormone therapies, and one or two chemotherapeutic agents. Also described is the use in a method of treating papillary or anaplastic thyroid cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from thyroid hormone pills, Doxorubucin and a platin. Also described is the use in method of treating papillary or anaplastic thyroid cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is hormone therapy and the hormone therapy is radioiodine ablation.

[0179] Also described is the use in a method of treating endometrial cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery, radiation, one or two hormone therapies, and one or two chemotherapeutic agents. Also described is the use in a method of treating endometrial cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two hormone therapies independently selected from megestrol acetate, Tamoxifen, and a progestin including medroxyprogesterone acetate (Provera) and megestrol acetate (Megace). Also described is the use in a method of treating endometrial cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from a platinum-containing compound (including cisplatin, oxaliplatin, and carboplatin, more for example cisplatin), a taxane (including paclitaxel), doxorubicin (Adriamycin), cyclophosphamide, fluorouracil (5-FU), methotrexate, and vinblastine.

[0180] Also described is the use in a method of treating ovarian cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery, radiation, or two antibodies, and one or two chemotherapeutic agents. Also described is the use in a method of treating ovarian cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is an antibody and the antibody is bevacizumab. Also described is the use in a method of treating ovarian cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from a platinum-containing compound (including cisplatin, oxaliplatin and carboplatin), a taxane (including paclitaxel and docetaxel), topotecan, an anthracyclines (including doxorubicin and liposomal doxorubicin), gemcitabine, cyclophosphamide, vinorelbine (Navelbine), hexamethylmelamine, ifosfamide, etoposide, bleomycin, vinblastine, ifosfamide, vincristine, and cyclophosphamide. Also described is the use in a method of treating ovarian cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from a platin and a taxane. Also described is the use in a method of treating ovarian cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from cisplatin, oxaliplatin, carboplatin, paclitaxel, and docetaxel.

[0181] Also described is the use in a method of treating glioblastoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery, radiation, one or two chemotherapeutic agents, one or two anti-seizure agents, and one or two agents to reduce swelling. Also described is the use in a method of treating glioblastoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is radiation selected from external beam radiation, interstitial radiotherapy, and stereotactic radiosurgery. Also described is the use in a method of treating glioblastoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from carmustine (BCNU), Erlotinib (Tarceva), bevacizumab, gefitinib (Iressa), rapamycin, temozolomide, cisplatin, BCNU, lomustine, procarbazine, and vincristine. Also described is the use in a method of treating glioblastoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is an anti-seizure agent and the anti-seizure agent is diphenylhydantoin (Dilantin). Also described is the use in a method of treating glioblastoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is an agents to reduce swelling and the agent is dexamethasone (Decadron). Also described is the use in a method of treating glioblastoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatements where one of the treatments is one or two chemotherapeutic agents. Also described is the use in a method of treating glioblastoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from erlotinib and temozolomide.

[0182] Also described is the use in a method of treating cervical cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery, radiation, and one or two chemotherapeutic agents. Also described is the use in a method of treating cervical cancer which method comprises administering to patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is surgery selected from cryosurgery, laser surgery, loop electrosurgical excision, conization, simple hysterectomy, and radical hysterectomy and pelvic lymph node dissection. Also described is the use in a method of treating cervical cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined, in combination with one or more treatments where one of the treatments is radiation selected from called external beam radiation therapy and brachytherapy. Also described is the use in a method of treating cervical cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from a platinum compound (such as cisplatin, carboplatin, and oxaliplatin), paclitaxel, topotecan, ifosfamide, gemcitabine, vinorelbine, and fluorouracil.

[0183] Also described is the use in a method of treating a gastrointestinal carcinoid tumor which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery, radiation, immunotherapy and one or two chemotherapeutic agents. Also described is a method of treating a gastrointestinal carcinoid tumor which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is surgery selected from excision and electrofulguration. Also described is the use in a method of treating a gastrointestinal carcinoid tumor which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from cyproheptadine, SOM230, octreotide and lanreotide. Also described is the use in a method of treating a gastrointestinal carcinoid tumor which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is immunotherapy and the immunotherapy is an interferon.

[0184] Also described is the use in a method of treating a gastrointestinal stromal tumor which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery, radiation, and one or two chemotherapeutic agents. Also described is the use in a method of treating a gastrointestinal stromal tumor which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from imatinib mesylate (Gleevec), sunitinib (Sutent), and nilotinib (AMN107).

[0185] Also described is the use in a method of treating hepatocellular carcinoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from surgery, radiofrequency ablation, ethanol ablation, cryosurgery, hepatic artery embolization, chemoembolization, radiation, and one or two chemotherapeutic agents. Also described is the use in a method of treating hepatocellular carcinoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is surgery selected from resection and transplantation. Also described is the use in a method of treating hepatocellular carcinoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents independently selected from sorafenib, 5-fluorouracil and cisplatin.

[0186] Also described is the use in a method of treating non-Hodgkin's lymphoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments independently selected from radiation, one or two chemotherapeutic agents, interferon therapy, one or two antibodies, and bone marrow or peripheral blood stem cell transplantation. Also described is the use in a method of treating non-Hodgkin's lymphoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is one or two chemotherapeutic agents selected from CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), chlorambucil, fludarabine, and etoposide. Also described is the use in a method of treating non-Hodgkin's lymphoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is an antibody selected from rituximab, ibritumomab tiuxetan, tositumomab, and alemtuzumab. Also described is the use in a method of treating non-Hodgkin's lymphoma which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is an antibody and the antibody is rituximab.

[0187] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is radiation and another treatment is surgery.

[0188] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is radiation and another treatment is one or two chemotherapeutic agents.

[0189] Also described is the use in a method of treating cancer which method comprises administering to a patient a therapeutically effective amount of a Compound of Formula I, as defined above, in combination with one or more treatments where one of the treatments is surgery and another treatment is one or two chemotherapeutic agents.

[0190] For each of the foregoing, the Compound of Formula I is selected from any of the following described compounds, including from the Representative Compounds in Table 1.

[0191] One described compound (A) is directed to a compound of Formula I where W¹, W², W³, and W⁴ are -C(R¹)=; or one or two of W¹, W², W³, and W⁴ are independently -N= and the remaining are -C(R¹)=; where each R¹ is independently hydrogen, alkyl, haloalkyl, nitro, alkoxy, haloalkoxy, halo, hydroxy, cyano, amino, alkylamino, or dialkylamino; and all other groups are as defined above. In another embodiment, W¹, W², W³, and W⁴ are -C(R¹)= and each R¹ is independently hydrogen or alkyl; or one of W¹ and W⁴ is -N= and the other is -C(H)=. In another , W¹, W², W³, and W⁴ are -C(R¹)= where each R¹ is independently hydrogen or alkyl. In another embodiment, R¹ is hydrogen.

[0192] Another (B) is a Compound of Formula I where R⁵⁰ is hydrogen, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, nitro, amino, alkylamino, dialkylamino, -N(R⁵⁵)C(O)-C₁-C₆-alkylene-N(R^55a)R^55b, alkylcarbonyl, alkenylcarbonyl, carboxy, alkoxycarbonyl, cyano,
alkylthio, -S(O)₂NR⁵⁵R^55a, or alkylcarbonylamino; where R⁵⁵ and R^55b are indepedently hydrogen, alkyl, or alkenyl and R^55a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy; and all other groups are as defined above. In another, R⁵⁰ is hydrogen.

[0193] Another (C) is a Compound of formula I where R⁵¹ is hydrogen or alkyl; and all other groups are as defined above. In another, R⁵¹ is alkyl, In another, R⁵¹ is methyl.

[0194] Another (D) is a Compound of Formula I where R⁵² is hydrogen or halo; and all other groups are as defined above. In another R⁵² is hydrogen or fluoro. In another embodiment, R⁵² is hydrogen.

[0195] Another (E) is a Compound of Formula I where R⁵³ is hydrogen, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, nitro, amino, alkylamino, dialkylamino, -N(R⁵⁵)C(O)-C₁-C₆-alkylene-N(R^55a)R^55b, alkylcarbonyl, alkenylcarbonyl, carboxy, alkoxycarbonyl, cyano, alkylthio, -S(O)₂NR⁵⁵R^55a, or alkylcarbonylamino; where R⁵⁵ and R^55b are independently hydrogen, alkyl, or alkenyl and R^55a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy; and all other groups are as defined above. In another, R⁵³ is hydrogen, alkoxy, nitro, amino, or -N(R⁵⁵)C(O)-C₁-C₆-alkylene-N(R^55a)R^55b. In another, R⁵³ is hydrogen, methoxy, nitro, amino, or -NHC(O)CH₂N(CH₃)₂. In another, R⁵³ is hydrogen or methoxy.

[0196] Another (F) is a Compound of Formula I where R⁵⁴ is hydrogen, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, nitro, amino, alkylamino, dialkylamino, -N(R⁵⁵)C(O)-C₁-C₆-alkylene-N(R^55a)R^55b, alkylcarbonyl, alkenylcarbonyl, carboxy, alkoxycarbonyl, cyano,
alkylthio, -S(O)₂NR⁵⁵R^55a, or alkylcarbonylamino; where R⁵⁵ and R^55b are indepedently hydrogen, alkyl, or alkenyl and R^55a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy; and all other groups are as defined above. In another, R⁵⁴ is hydrogen, alkyl, alkoxy, or halo. In another, R⁵⁴ is hydrogen, methyl, methoxy, bromo, or chloro. In another, R⁵⁴ is hydrogen, methoxy, or chloro.

[0197] Another (G) is a compound of Formula I where R⁵⁰, R⁵², and R⁵³ are hydrogen and R⁵⁴ is halo or alkoxy; R⁵⁰, R⁵², and R⁵⁴ are hydrogen and R⁵³ is alkoxy; or R⁵⁰ and R⁵² are hydrogen and R⁵³ and R⁵⁴ together with the carbons to which they are attached form a 6-membered heteroaryl; and all other groups are as defined above. In another, R⁵⁰, R⁵², and R⁵³ are hydrogen and R⁵⁴ is chloro or methoxy; R⁵⁰, R⁵², and R⁵⁴ are hydrogen and R⁵³ is methoxy; or R⁵⁰ and R⁵² are hydrogen and R⁵³ and R⁵⁴ together with the carbons to which they are attached form pyridinyl. Even more speicfically, R⁵⁰, R⁵², and R⁵³ are hydrogen and R⁵⁴ is chloro or methoxy; or R⁵⁰, R⁵², and R⁵⁴ are hydrogen and R⁵³ is methoxy.

[0198] One compound of the compound of the paragraph above (G1) is a compound of formula I where R⁵¹ is methyl.

[0199] Another described compound (H) is a compound of Formula I where B is phenyl substituted with R^3a and optionally further substituted with one, two, or three R³; and all other groups are as defined above. In another, B is phenyl substituted with R^3a. In another the Compound is of Formula I(a):

In another, B is phenyl substituted with R^3a as depicted in Ia and is not further substituted with R³.

[0200] Another described compound (J) a compound of Formula I where B is heteroaryl optionally substituted with one, two, or three R³. In another embodiment, B is thien-3-yl, pyridinyl, pyrimidinyl, pyridazinyl, pyrazinyl, oxazolyl, isoxazolyl, pyrrolyl, imidazolyl, pyrazolyl, or thiazolyl, each of which is optionally substituted with one or two R³. In another embodiment, B is thien-3-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, imidazol-2-yl, pyrrol-2-yl, pyrrol-3-yl, imidazol-4-yl, imidazol-5-yl, pyrazol-3-yl, pyrazol-4-yl, or pyrazol-5-yl, each of which is optionally substituted with one or two R³. In another embodiment, B is thien-3-yl, pyridin-3-yl, pyridin-4-yl, isoxazol-4-yl, or pyrazol-4-yl, each of which is optionally substituted with one or two R³. In another, B is pyridin-3-yl, 2-hydroxy-pyridin-5-yl, isoxazol-4-yl, or pyrazol-4-yl, each of which is optionally substituted with one or two R³.

[0201] Another (K) is a compound of Formula I or Ia where R^3a is cyano; hydroxyamino; carboxy; alkylsulfonyl, aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; -N(R⁷)C(O)-C₁-C₆-alkylene-N(R^7a)(R^7b); -C(O)NR⁸R^8a; -NR⁹C(O)R^9a; -C(O)N(R¹⁰)-C₁-C₆-alkylene-N(R^10a)R^10b; -NR¹¹C(O)NR^11aR^11b where R^11a; -C(O)R¹²; -NR¹³C(O)OR^13a; -C(O)N(R¹⁴)N(R^14a)(R^14b); -S(O)₂N(R¹⁵)-C₁-C₆-alkylene-N(R^15a)R^15b; -C(O)N(R¹⁶)-C₁-C₆-alkylene-C(O)OR^16a; heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; -N(R¹⁷)-C(=N(R^17b)(R^17a)(NR^17cR^17d); -N(R¹⁸)C(O)-C₁-C₆-alkylene-N(R^18b)C(O)R^18a; -C(O)N(R¹⁹)-C₁-C₆-alkylene-C(O)R^19a; -N(R²²)C(O)-C₁-C₆-alkylene-N(R^22b)-N(R^22c)(R^22a); -C₀-C₆-alkylene-N(R²³)-C₁-C₆-alkylene-N(R^23b)R^23a; or -NR²⁴C(O)-C₁-C₆-alkylene-OR^24a; where each of the alkylene in R^3a is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, amino, alkylamino, and dialkylamino; and all other groups are as defined above.

[0202] In another, R^3a is -NHC(O)CH₂NH(CH₃), -NHC(O)CH₂NH(CH₂CH₃), -NHC(O)CH(CH₃)NH₂, -NHC(O)C(CH₃)₂NH₂, -NHC(O)CH₂N(CH₃)₂, -NHC(O)CH₂N(CH₃)CH₂CH₂N(CH₃)₂, -NHC (O)CH(NH₂)CH₂CH₃, -NHC(O)CH₂N(CH₃)CH₂CH₂N(CH₃)₂, -NHC(O)CH(CH₃)NH(CH₃), -NHC(O)CH₂NH₂, -NHC(O)H, -NHC(O)CH₂(azetidin-1-yl), -NHC(O)(pyrrolidin-2-yl), -NHC(O)CH(NH₂)CH₂OH, -NHC(O)(azetidin-4-yl), -NHC(O)C(CH₃)₂NH(CH₃), -NH₂, -NHC(O)CH₂NH(CH₂CH₂CH₃), -NHC(O)CH₂CH₂NH₂, -NHOH, -NHC(O)(piperidin-3-yl), -NHC(O)CH₂(4-methyl-1,4-diazepan-1-yl), -NHC(O)CH(NH₂)(CH₂CH₃), -NHC(O)CH₂NH(CH₂CH(OH)(CH₃)), -NHC(O)CH₂NHCH₂CH₂F, -NHC(O)CH₂NH(OCH₂CH(CH₃)₂), -NHC(O)(1-aminocycloprop-1-yl), -NHC(O)CH₂NH(CH₂cyclopropyl), -NHC(O)CH₂(3-(dimethylamino)-azetidin-1-yl), -NHC(O)(piperidin-2-yl), -NHC(O)(morpholin-4-yl), -NHC(O)CH₂(pyrrolidin-1-yl), -NHC(O)CH(NH₂)CH₂CH₂CH₂CH₂N(CH₃)₂, -NHC(O)CH₂N(CH₃)(CH₂CH₃), -NHC(O)CH₂(imidazol-5-yl), -NHC(O)(1-aminocyclopent-1-yl), -NHC(O)CH₂NH(CH₂CH(CH₃)₂), -NHC(O)CH₂N(CH₃)(CH₂CH₃), -NHC(O)(N-(imidazol-4-ylmethyl)-azetidin-3-yl), -NHC(O)(N-ethyl-azetidin-3-yl), -NHCH₂N(CH₃)CH₂CH₂N(CH₃)₂, -NHC(O)CH₂N(CH₃)(N-methyl-pyrrolidin-3-yl), -NHC(O)CH₂N(CH₃)(CH₂CH₂N(CH₃)₂), -NHC(O)CH₂(3-hydroxy-pyrrolidin-1-yl), -NHC(O)(1-amino-cyclobut-1-yl), -NHC(O)CH₂NH(CH₂)₃CH₃, -NHC(O)CH₂(3-piperidin-1-ylazetidin-1yl), -NHC(O)NH₂, -NHC(O)(1-hydroxycyclopropyl), -NHC(O)CH₂NHN(CH₃)₂, -NHC(O)NH(CH₂)₂N(CH₃)₂, -NHC(O)CH₂OH, -NHC(O)(pyridazin-4-yl), -NHC(O)(N-methyl-piperidin-4-yl), -NHC(O)CH₂NHCH(CH₃)₃, -NHC(O)CH₂(3-dimethylamino-pyrrolidin-lyl), -NHC(O)CH₂NH(CH₂)₂N(CH₃)₂, -NHC(O)(1-cyclopropylmethyl-azetidin-3-yl), -NHC(O)CH₂NH(CH₃)₃, -NHC(O)(imidazol-2-yl), -NHC(O)(imidazol-4-yl), -NHC(O)(1,2-oxaxol-5-yl), -NHC(O)CH₂NHCH₂CF₃, -NHC(O)CH₂CH₂(piperidin-1-yl), -NHC(O)(3-oxo-cyclopent-1-yl), -NHC(O)(2-hydroxy-pyridin-6-yl), -NHC(O)CH₂NH(3-fluoro-4-hydroxyphenyl), -NHC(O)(CH₂)₃N(CH₃)₂, -NHC(O)(1-(furan-2-ylmethyl)-azetidin-3-yl), -NHC(O)(pyrimidin-5-yl), -NHC(O)(pyrrol-2-yl), -NHC(O)CH₂N(CH₃)CH(CH₃)₂, -NHC(O)CH₂N(CH₂CH₃)₂, -NHC(O)CH₂(3-methyl-1,2-oxazol-5-yl), -NHC(O)CH₂NHCH₂(3-hydroxyphenyl), -NHC(O)(N-methyl-pyrrol-2-yl), -NHC(O)(2-amino-tetrahydropyran-2-yl), -NHC(O)CH₂(4-methylamino-piperidin-1-yl), -NHC(O)(piperidin-1-yl), -NHC(O)(N-methyl-pyrrolidin-2yl), -NHC(O)(thien-3yl), -NHC(O)(N-(cyclopropylcarbonyl)azetidin-3-yl), -NHC(O)CH₂(4-methylpiperazin-1-yl), -NHC(O)(N-benzylazetidin-3-yl), -NHC(O)(2-chloro-pyridin-3-yl), -NHC(O)CH₂(pyridin-4-yl), -NHC(O)CH₂N(CH₃)(CH₂CH=CH₂), -NHC(O)CH₂NH(benzyl), -NHC(O)CH₂OCH₃, -NHC(O)[1-(C(O)CH₂CH₃)-azetidin-3-yl], -NHC(O)(pyridin-3-yl), -NHC(O)CH₂NHCH₂CH₂OCH₃, -NHC(O)(1-[C(O)CH₃]piperidin-4-yl), -NHC(O)CH₂(2-methyl-pyrrolidin-1-yl), -NHC(O)(furan-3-yl), -NHC(O)CH₂N(CH₃)₂, -NHC(O)(2-chloro-pyridin-5-yl), -NHC(O)(2-chlorophenyl), -NHC(O)CH₂(pyridin-2-yl), -NHC(O)CH₂(3-dimethylamino-azetidin-1-yl), -NHC(O)CH₂(pyridin-3-yl), -NHC(O)CH₂(2-chlorophenyl), -NHC(O)CH₂N(CH₃)CH₂CH₂CH₂N(CH₃)₂, -NHC(O)CH₂N(CH₂CH₃)CH₂CH ₂OH, -NHC(O)CH₂(2-benzyl-pyrrolidin-1-yl), -NHC(O)(furan-2-yl, -NHC(O)(2-chloro-pyridin-4-yl), -NHC(O)CH₂NHC(O)CH₃, -NHC(O)CH₂CH₂CH₃, -NHC(O)(4-chlorophenyl), -NHC(O)(4-methyl-phenyl), -NHC(O)CH₂NHC(O)O(CH₃)₃, -NHC(O)(benzo[d][1,3]dioxol-5-yl), -NHC(O)CH₂NHOCH₂(2-methoxyphenyl), -NHC(O)(pyridin-4-yl), -NHC(O)CH₂[4-(3,4-dichlorophenyl)-piperazin-1-yl], -NHC(O)CH₂CH₂(pyridin-3-yl), -NHC(O)(tetrahydrofuran-3-yl), -NHC(O)CH₂NHCH₂(2-methylphenyl), -NHC(O)CH(CH₃)CH₂CH₃, -NHC(O)CH₂(3-fluorophenyl), -NHC(O)CH₂C(CH₃)₂phenyl, -NHC(O)(2-methyl-cycloprop-1-yl), -NHC(O)(2-methyl-4-methoxyphenyl), -NHC(O)(2-methylpyridin-3-yl), -NHC(O)(4-methoxyphenyl), -NHC(O)CH₂(4-ethylpiperazin-1-yl), -NHC(O)(thien-2-yl), -NHC(O)(3-fluoro-2-methylphenyl), -NHC(O)(2-bromo-thien-3-yl), -NHC(O)(4-fluorophenyl), -NHC(O)CH₂(3-methylpiperidin-1-yl), -NHC(O)CH(CH₃)₂, -NHC(O)(CH₂)₃CH₃, -NHC(O)CH₂OCH₂CH₃, -NHC(O)CH₂NH(2-fluorophenyl), -NHC(O)(3-dimethylaminophenyl), -NHC(O)CH₂(4-methylpiperidin-1-yl), -NHC(O)CH₂NH(2-n-propylphenyl), -NHC(O)phenyl, -NHC(O)(pyrazin2-yl), -NHC(O)(3-fluoro-4-methoxyphenyl), -NHC(O)C(CH₃)₂CH₂CH₃, -NHC(O)CH₂O(4-fluorophenyl), -NHC(O)(1-methylcarbonyl-azetidin-3-yl), -NHC(O)CH₂NH(4-methylphenyl), -NHC(O)CH₂NH(phenyl), -NHC(O)CH₂(4-allyl-piperazin-1-yl), -NHC(O)(2-methylphenyl), -NHC(O)CH₂CH₂OCH₃, -NHC(O)(3-methylfuran-2-yl), -NHC(O)C(CH₃)₃, -NHC(O)CH₂NHObenzyl, -NHC(O)CH₂NH(3-chlorophenyl), -NHC(O)cyclobutyl, -NHC(O)CH₂(3-methoxyphenyl), -NHC(O)(1-methylcycloprop-1-yl), -NHC(O)(3-flurophenyl), -NHC(O)(4-dimethylaminophenyl), -NHC(O)(3,4-dichlorophenyl), -NHC(O)CH₂NHCH₂(2-methylthiophenyl), -NHC(O)CH₂(2-fluorophenyl), -NHC(O)CH₂N(CH₂CH₃)CH(CH₃)₂, -NHC(O)(thiazol-4-yl), -NHC(O)CH₂N(CH₃)benzyl, -NHC(O)CH₂NHCH₂(thien-2-yl), -NHC(O)CH₂NHCH₂(pyridin-2-yl), -NHC(O)(3-methoxyphenyl), -NHC(O)CH₂NHCH₂(3-chloro-4-methylphenyl), -NHC(O)CH(CH₃)CH₂CH₂CH₃, -NHC(O)CH₂(4-chlorophenyl), -NHC(O)(3-fluoro-4-methylphenyl), -NHC(O)CH₂O(2-methylphenyl), -NHC(O)CH₂(cyclohexyl), -NHC(O)(2-phenyl-cycloprop-1-yl), -NHC(O)(3-chlorophenyl), -NHC(O)CH₂(2-methoxyphenyl), -NHC(O)CH₂CH₂(3-methoxyphenyl), -NHC(O)CH₂NH(2-fluoro-4-methyl-phenyl), -NHC(O)CH₂NHCH₂(3-fluoro-phenyl), -NHC(O)CH₂(4-methoxy-phenyl), -NHC(O)benzyl, -NHC(O)(2,4-dichlorophenyl), -NHC(O)(3-oxo-cyclohex-1-yl), -NHC(O)CH₂NH(3-fluorophenyl), -NHC(O)CH₂(3-chlorophenyl), -NHC(O)CH₂NHCH₂CH(CH₃)phenyl, -NHC(O)CH₂NHCH₂(2,4-dimethylphenyl), -NHC(O)CH₂(2-methyl-piperidin-1-yl), -NHC(O)CH₂NH(2-methoxyphenyl), -NHC(O)CH₂(1,2,3,4-tetrahydroisoquinolin-2-yl), -NHC(O)CH₂CH₂CH=CH₂, -NHC(O)CH₂NH(2-methylphenyl), -NHC(O)CH₂(4-oxo-piperidin-1-yl), -NHC(O)(2-fluorophenyl), -NHC(O)CH₂NHCH(CH₃)phenyl, -NHC(O)(2-fluoro-6-methoxyphenyl), -NHC(O)CH₂NH(2-isopropylphenyl), -NHC(O)CH₂CH₂(2-methoxyphenyl), -NHC(O)CH₂CH₂CH(CH₃)₂, -NHC(O)CH₂(2-phenyl-morpholin-4-yl), -NHC(O)CH₂CH₂(4-methoxyphenyl), -NHC(O)CH₂N(allyl)cyclopentyl, -NHC(O)CH₂N(CH₃)CH₂CH₂OCH₃, -NHC(O)CH₂CH₂C(O)cyclopropyl, -NHC(O)CH₂NH(3-tert-butylphenyl), -NHC(O)CH₂N(n-propyl)(cyclopropylmethyl), -NHC(O)CH₂(2-oxo-cyclopentyl), -NHC(O)CH₂NH(4-chlorophenyl), -NHC(O)CH₂(4-piperidin-1-ylpiperidin-1-yl), -NHC(O)CH₂(4-cyclopentylpiperazin-1-yl), -NHC(O)CH₂(2-methylphenyl), -NHC(O)CH₂NHCH₂(3-fluoro-6-methylphenyl), -NHC(O)CH₂C(CH₃)₃, -NHC(O)CH₂NH(2-chlorophenyl), -NHC(O)(3-fluoro-6-methylphenyl), -NHC(O)(4-fluoro-3-methylphenyl), -NHC(O)(2,3-dichlorophenyl), -NHC(O)CH₂Ophenyl, -NHC(O)CH₂NH(2,3-dimethylphenyl), -NHC(O)(2-fluoro-5-methylphenyl), -NHC(O)CH₂NHOCH₂(4-methylphenyl), -NHC(O)CH₂(4-isopropylpiperazin-1-yl), -NHC(O)CH₂(4-fluorophenyl), -NHC(O)CH₂CH(CH₃)₂, -NHC(O)(2-methoxy-4-methylphenyl), -NHC(O)CH₂(4-n-propylpiperidin-1-yl), -NHC(O)CH₂O(3-methylphenyl), -NHC(O)(tetrahydrofuran-2-yl), -NHC(O)CH₂(3-hydroxymethylpiperidin-1-yl), -NHC(O)(1-tert-butoxycarbonylpiperidin-2-yl), -NHC(O)CH₂N(CH₃)CH₂(pyridin-3-yl), -NHC(O)CH₂N(CH₂CH₃)phenyl, -NHC(O)CH₂OCH₂CH₂OCH₃, -NHC(O)CH₂CH₂(cyclopentyl), -NHC(O)(2,5-dichlorophenyl), -NHC(O)CH₂(4-methylcarbonylpiperazin-1-yl), -NHC(O)(5-fluoro-2-methoxyphenyl), -NHC(O)CH₂N(CH₂CH₃)cyclohexyl, -NHC(O)(5-methyl-1,2-oxazol-3-yl), -NHC(O)(3-methylpyridin-3-yl), -NHC(O)(2-methoxypyridin-3-yl), -NHC(O)(3,5-dichlorophenyl), -NHC(O)CH₂(thiazolidin3-yl), -NHC(O)CH₂(4-[C(O)H]-piperazin-1-yl), -NHC(O)CH₂(2-pyridin-4-ylpiperidin-1-yl), -NHC(O)(2-methoxyphenyl), -NHC(O)CH₂N(CH₃)CH₂CH(CH₃)₂, -NHC(O)CH₂(4-[C(O)H]-homopiperazin-1-yl), -NHC(O)(1-phenylcycloprop-1-yl), -NHC(O)CH₂(2,6-dimethylmorpholin-4-yl), NHC(O)CH₂(2-phenylpyrrolidin-1-yl), -NHC(O)CH₂(morpholin-4-yl), -C(O)NHCH(CH₃)CH₂N(CH₃)₂, -C(O)NHCH₂CH₂N(CH₃)₂, -C(O)NH(pyrrolidin-3-yl), -C(O)NHCH₂CH₂(pyrrolidin-1-yl), -C(O)NHCH₂CH₂NH₂, -C(O)N(CH₃)CH₂CH₂N(CH₃)₂, -C(O)NHCH₂(piperidin-2-yl), -C(O)NH(1-methylazetidin-3-yl), -C(O)NHCH₂CH₂(piperidin-1-yl), -C(O)NHCH₂CH₂N(CH₂CH₃)₂, -C(O)NH(1-methylpiperidin-3-yl), -C(O)NH(piperidin-3-yl), -C(O)NHCH₂(1-methylpiperidin-3-yl), -C(O)NHCH₂CH₂N(CH₂CH₂OH)₂, -C(O)NH(1-ethylpiperidin-3-yl), -C(O)NH₂, -C(O)(3-aminopyrrolidin-1-yl), -C(O)(3-methylaminopyrrolidin-1-yl), -C(O)OH, -C(O)NHCH₂CH₂(morpholin-4-yl), -C(O)NHCH₂(1-ethylpyrrolidin-2-yl), -C(O)(4-amino-3-oxo-pyrazolidin-1-yl), -C(O)NHCH₃, -C(O)(3-aminocyclobut-1-yl), -C(O)NHCH₂(pyridin-3-yl), -C(O)NHCH₂CH₂OH, -C(O)NH(3-oxo-pyrazolidin-4-yl), -NHCH₂CH₂(imidazol-4-yl), -C(O)(3-dimethylaminopyrrolidin-1-yl), -C(O)NHCH₂(pyridin-4-yl), -C(O)N(CH₃)(1-methyl-pyrrolidin-3-yl), -C(O)(3-diethylaminopyrrolidin-1-yl), -C(O)NH(pyrrol-1-yl), -C(O)NHCH₂CH₂CH₂(pyrrolidin-1-yl), -C(O)N(CH₃)CH₂CH₂CN, -C(O)NHCH₂CH₂OCH₃, -C(O)N(CH₂CH₃)CH₂CH₂CN, -C(O)(3-aminopiperidin-1-yl), -C(O)NHCH₂CH₂CH₂N(CH₃)₂, -C(O)NH(morpholin-4-yl), -C(O)NHN(CH₃)₂, -C(O)NHCH₂CH₂CH₂(imidazol-1-yl), -C(O)NHCH₂CH₂CH₂N(CH₂CH₃)₂, -C(O)NHCH₂CH₂CN, -C(O)NHCH₂CH₂C(O)OCH₃, -C(O)NHCH₂CH₂SCH₃, -C(O)NHCH₂CH₂SCH₂CH₃, -C(O)N(CH₂CH₃)CH₂CH₂N(CH₃)₂, -C(O)NHCH₂CH₂CH₂(2-oxo-pyrrolidin-1-yl), -C(O)NHCH₂CH₂(pyridin-4-yl), -C(O)NHCH₂CH₂CH₂OCH₂CH₃, -C(O)NHCH₂CH₂CH₂(morpholin-4-yl), -C(O)NHCH₂CH₂CH₂OCH₃, -C(O)N(CH₃)CH₂CH₂CH₂N(CH₃)₂, -C(O)NHCH₂CH₂CH₂OCH₂CH₂CH₃, -C(O)NHCH₂CH₂C(O)OCH₂CH₃, -C(O)NHCH₂CH₂CH₂OCH(CH₃)₂, -C(O)NHC(CH₃)₂CH₂(piperidin-1-yl), -C(O)N(CH₃)CH₂CH₂CH₃, -C(O)NH(piperidin-1-yl), -C(O)NHCH(CH₃)CH₂OCH₃, -C(O)NHC(CH₃)₂CH₂(morpholin-4-yl), -C(O)(2-dimethylaminomethylpiperidin-1-yl), -C(O)NH(CH₂)₃O(CH₂)₃CH₃, -C(O)NHCH(CH₃)(CH₂)₃N(CH₂CH₃)₂, -C(O)NHC(CH₃)₂C(O)(piperidin-1-yl), -C(O)(4-methylpiperazin-1-yl), -C(O)(2-piperidin-1-ylmethyl-piperidin-1-yl), cyano, -NHCH₃, -CH(CH₃)NHCH₂CH₂N(CH₃)₂, -C(O)CH₃, -S(O)₂NHCH₂CH₂N(CH₃)₂, -S( O)₂NH(CH₂)₃N(CH₃)₂, 5-(N,N-dimethylaminomethyl)-1,3,4-oxadiazol-2-yl, -NHCH₂CH₂N(CH₃)₂, -N(CH₃)₂, -OCH₂CH₂N(CH₃)₂, -NHC[N(CH₃)₂][=N(CH₃)₂], -OCH F₂, -S(O)₂CH₃, -OCF₃, or -NHC(O)CH₂(4-dimethylaminopiperidin-1-yl).

[0203] In another (L), the compound of Formula I or Ia is that where R^3a is hydroxyamino, -N(R⁷)C(O)-C₁-C₆-alkylene-N(R^7a)(R^7b), -C(O)NR⁸R^8a, -NR⁹C(O)R^9a, -C(O)N(R¹⁰)-C₁-C₆-alkylene-N(R^10a)R^10b, -NR¹¹C(O)NR^11aR^11b, -N(R²²)C(O)-C₁-C₆-alkylene-N(R^22b)-N(R^22c)(R^22a), -NR¹³C(O)OR^13a, -N(R¹⁸)C(O)-C₁-C₆-alkylene-N(R^18b)C(O)R^18a, -NR²⁴C(O)-C₁-C₆-alkylene-OR^24a, or -N(R²⁰)C(O)-C₁-C₆-alkylene-C(O)R^20a; where each of the alkylene in R^3a is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; and all other groups are as defined above. In another, R^3a is -NHC(O)CH₂NH(CH₃), -NHC(O)CH(CH₃)NH₂, -NHC(O)C(CH₃)₂NH₂, -NHC(O)CH₂N(C H₃)₂, -NHC(O)CH₂N(CH₃)CH₂CH₂N(CH₃)₂, -NHC(O)CH(NH₂)CH₂CH₃, -NHC(O)CH₂N(C H₃)CH₂CH₂N(CH₃)₂, -NHC(O)CH(CH₃)NH(CH₃), -NHC(O)H, -NHC(O)CH₂(azetidin-1-yl), -NHC(O)(pyrrolidin-2-yl), -NHC(O)CH(NH₂)CH₂OH, -NHC(O)(azetidin-4-yl), -NHC(O)C(CH₃)₂NH(CH₃), -NH₂, -NHC(O)CH₂NH(CH₂CH₂CH₃), -NHC(O)CH₂CH₂NH₂ -NHOH, or -NHC(O)(piperidin-3-yl).

[0204] In another (M) the compound is of Formula I or Ia and R^3a -N(R⁷)C(O)-C₁-C₆-alkylene-N(R^7a)(R^7b); and R⁷ is hydrogen or alkyl and R^7a and R^7b are independently hydrogen, alkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; and all other groups are as defined above. In another, R^3a is -NHC(O)CH₂NH(CH₃), -NHC(O)CH(CH₃)NH₂, -NHC(O)C(CH₃)₂NH₂, -NHC(O)CH₂N(CH₃)₂, -NHC(O)CH₂N(CH₃)CH₂CH₂N(CH₃)₂, -NHC(O)CH(NH₂)CH₂CH₃, -NHC(O)CH₂N(CH₃)CH₂CH₂N(CH₃)₂, or -NHC(O)CH(CH₃)NH(CH₃).

[0205] Another described compound (N) is a compound of Formula I where each R³ is independently halo; cyano; alkyl; alkenyl; alkoxy; hydroxyamino; carboxy; alkylsulfonyl, aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; -N(R⁷)C(O)-C₁-C₆-alkylene-N(R^7a)(R^7b); -C(O)NR⁸R^8a; -NR⁹C(O)R^9a; -C(O)N(R¹⁰)-C₁-C₆-alkylene- N(R^10a)R^10b; -NR¹¹C(O)NR^11aR^11b where R^11a; -C(O)R¹²; -NR¹³C(O)OR^13a; -C(O)N(R¹⁴)N(R^14a)(R^14b); -S(O)₂N(R¹⁵)-C₁-C₆-alkylene-N(R^15a)R^15b; -C(O)N(R¹⁶)-C₁-C₆-alkylene-C(O)OR^16a; heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; -N(R¹⁷)-C(=N(R^17b)(R^17a))(NR^17cR^17d); -N(R¹⁸)C(O)-C₁-C₆-alkylene-N(R^18b)C(O)R^18a; -C(O)N(R¹⁹)-C₁-C₆-alkylene-C(O)R^19a; -N(R²²)C(O)-C₁-C₆-alkylene-N(R^22b)-N(R^22c)(R^22a); -C_0-C₆-alkylene-N(R²³)-C₁-C₆-alkylene-N(R^23b)R^23a; or -NR²⁴C(O)-C₁-C₆-alkylene-OR^24a; where each of the alkylene in R³ is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, amino, alkylamino, and dialkylamino; and all other groups are as defined above.

[0206] In another described compound, each R³ is independently methyl, bromo, chloro, fluoro, -NHC(O)CH₂NH(CH₃), -NHC(O)CH₂NH(CH₂CH₃), -NHC(O)CH(CH₃)NH₂, -NHC(O)C(CH₃)₂NH₂, -NHC(O)CH₂N(CH₃)₂, -NHC(O)CH₂N(CH₃)CH₂CH₂N(CH₃)₂, -NHC(O)CH(NH₂)CH₂CH₃, -NHC(O)CH₂N(CH₃)CH₂CH₂N(CH₃)₂, -NHC(O)CH(CH₃)NH(CH₃), -NHC(O)CH₂NH₂, -NHC(O)H, -NHC(O)CH₂(azetidin-1-yl), -NHC(O)(pyrrolidin-2-yl), -NHC(O)CH(NH₂)CH₂OH, -NHC(O)(azetidin-4-yl), -NHC(O)C(CH₃)₂NH(CH₃), -NH₂, -NHC(O)CH₂NH(CH₂CH₂CH₃), -NHC(O)CH₂CH₂NH₂, -NHOH, -NHC(O)(piperidin-3-yl), -NHC(O)CH₂(4-methyl-1,4-diazepan-1-yl), -NHC(O)CH(NH₂)(CH₂CH₃), -NHC(O)CH₂NH(CH₂CH(OH)(CH₃)), -NHC(O)CH₂NHCH₂CH₂F, -NHC(O)CH₂NH(OCH₂CH(CH₃)₂), -NHC(O)(1-aminocycloprop-1-yl), -NHC(O)CH₂NH(CH₂cyclopropyl), -NHC(O)CH₂(3-(dimethylamino)-azetidin-1-yl), -NHC(O)(piperidin-2-yl), -NHC(O)(morpholin-4-yl), -NHC(O)CH₂(pyrrolidin-1-yl), -NHC(O)CH(NH₂)CH₂CH₂CH₂CH₂N(CH₃)₂, -NHC(O)CH₂N(CH₃)(CH₂CH₃), -NHC(O)CH₂(imidazol-5-yl), -NHC(O)(1-aminocyclopent-1-yl), -NHC(O)CH₂NH(CH₂CH(CH₃)₂), -NHC(O)CH₂N(CH₃)(CH₂CH₃), -NHC(O)(N-(imidazol-4-ylmethyl)-azetidin-3-yl), -NHC(O)(N-ethyl-azetidin-3-yl), -NHCH₂N(CH₃)CH₂CH₂N(CH₃)₂, -NHC(O)CH₂N(CH₃)(N-methyl-pyrrolidin-3-yl), -NHC(O)CH₂N(CH₃)(CH₂CH₂N(CH₃)₂), -NHC(O)CH₂(3-hydroxy-pyrrolidin-1-yl), -NHC(O)(1-amino-cyclobut-1-yl), -NHC(O)CH₂NH(CH₂)₃CH₃, -NHC(O)CH₂(3-piperidin-1-ylazetidin-lyl), -NHC(O)NH₂, -NHC(O)(1-hydroxycyclopropyl), -NHC(O)CH₂NHN(CH₃)₂, -NHC(O)NH(CH₂)₂N(CH₃)₂, -NHC(O)CH₂ OH, -NHC(O)(pyridazin-4-yl), -NHC(O)(N-methyl-piperidin-4-yl), -NHC(O)CH₂NHCH(CH₃)₃, -NHC(O)CH₂(3-dimethylamino-pyrrolidin-1yl), -NHC(O)CH₂NH(CH₂)₂N(CH₃)₂, -NHC(O)(1-cyclopropylmethyl-azetidin-3-yl), -NHC(O)CH₂NH(CH₃)₃, -NHC(O)(imidazol-2-yl), -NHC(O)(imidazol-4-yl), -NHC(O)(1,2-oxazol-5-yl), -NHC(O)CH₂NHCH₂CF₃, -NHC(O)CH₂CH₂(piperidin-1-yl), -NHC(O)(3-oxo-cyclopent-1-yl), -NHC(O)(2-hydroxy-pyridin-6-yl), -NHC(O)CH₂NH(3-fluoro-4-hydroxyphenyl), -NHC(O)(CH₂)₃N(CH₃)₂, -NHC(O)(1-(furan-2-ylmethyl)-azetidin-3-yl), -NHC(O)(pyrimidin-5-yl), -NHC(O)(pyrrol-2-yl), -NHC(O)CH₂N(CH₃)CH(CH₃)₂, -NHC(O)CH₂N(CH₂CH₃)₂, -NHC(O)CH₂(3-methyl-1,2-oxazol-5-yl), -NHC(O)CH₂NHCH₂(3-hydroxyphenyl), -NHC(O)(N-methyl-pyrrol-2-yl), -NHC(O)(2-amino-tetrahydropyran-2-yl), -NHC(O)CH₂(4-methylamino-piperidin-1-yl), -NHC(O)(piperidin-1-yl), -NHC(O)(N-methyl-pyrrolidin-2yl), -NHC(O)(thien-3yl), -NHC(O)(N-(cyclopropylcarbonyl)azetidin-3-yl), -NHC(O)CH₂(4-methylpiperazin-1-yl), -NHC(O)(N-benzylazetidin-3-yl), -NHC(O)(2-chloro-pyridin-3-yl), -NHC(O)CH₂(pyridin-4-yl), -NHC(O)CH₂N(CH₃)(CH₂CH=CH₂), -NHC(O)CH₂NH(benzyl), -NHC(O)CH₂OCH₃, -NHC(O)[1-(C(O)CH₂CH)-azetidin-3-yl], -NHC(O)(pyridin-3-yl), -NHC(O)CH₂NHCH₂CH₂OCH₃, -NHC(O)(1-[C(O)CH3]piperidin-4-yl), -NHC(O)CH₂(2-methyl-pyrrolidin-1-yl), -NHC(O)(furan-3-yl), -NHC(O)CH₂N(CH₃)₂, -NHC(O)(2-chloro-pyridin-5-yl), -NHC(O)(2-chlorophenyl), -NHC(O)CH₂(pyridin-2-yl), -NHC(O)CH₂(3-dimethylamino-azetidin-1-yl), -NHC(O)CH₂(pyridin-3-yl), -NHC(O)CH₂(2-chlorophenyl), -NHC(O)CH₂N(CH₃)CH₂CH₂CH₂N(CH₃)₂, -NHC(O)CH₂N(CH₂CH₃)CH₂CH₂OH, -NHC(O)CH₂(2-benzyl-pyrrolidin-1-yl), -NHC(O)(furan-2-yl, -NHC(O)(2-chloro-pyridin-4-yl), -NHC(O)CH₂NHC(O)CH₃, -NHC(O)CH₂CH₂CH₃, -NHC(O)(4-chlorophenyl), -NHC(O)(4-methylphenyl), -NHC(O)CH₂NHC(O)O(CH₃)₃, -NHC(O)(benzo[d][1,3]dioxol-5-yl), -NHC(O)CH₂NHOCH₂(2-methoxyphenyl), -NHC(O)(pyridin-4-yl), -NHC(O)CH₂[4-(3,4-dichlorophenyl)-piperazin-1-yl], -NHC(O)CH₂CH₂(pyridin-3-yl), -NHC(O)(tetrahydrofuran-3-yl), -NHC(O)CH₂NHCH₂(2-methylphenyl), -NHC(O)CH(CH₃)CH₂CH₃, -NHC(O)CH₂(3-fluorophenyl), -NHC(O)CH₂C(CH₃)₂phenyl, -NHC(O)(2-methyl-cycloprop-1-yl), -NHC(O)(2-methyl-4-methoxyphenyl), -NHC(O)(2-methylpyridin-3-yl), -NHC(O)(4-methoxyphenyl), -NHC(O)CH₂(4-ethylpiperazin-1-yl), -NHC(O)(thien-2-yl), -NHC(O)(3-fluoro-2-methylphenyl), -NHC(O)(2-bromo-thien-3-yl), -NHC(O)(4-fluorophenyl), -NHC(O)CH₂(3-methylpiperidin-1-yl), -NHC(O)CH(CH₃)₂, -NHC(O)(CH₂)₃CH₃, -NHC(O)CH₂OCH₂CH₃, -NHC(O)CH₂NH( 2-fluorophenyl), -NHC(O)(3-dimethylaminophenyl), -NHC(O)CH₂(4-methylpiperidin-1-yl), -NHC(O)CH₂NH(2-n-propylphenyl), -NHC(O)phenyl, -NHC(O)(pyrazin2-yl), -NHC(O)(3-fluoro-4-methoxyphenyl), -NHC(O)C(CH₃)₂CH₂CH₃, -NHC(O)CH₂O(4-fluorophenyl), -NHC(O)(1-methylcarbonyl-azetidin-3-yl), -NHC(O)CH₂NH(4-methylphenyl), -NHC(O)CH₂NH(phenyl), -NHC(O)CH₂(4-allyl-piperazin-I-yl), -NHC(O)(2-methylphenyl), -NHC(O)CH₂CH₂OCH₃, -NHC(O)(3-methyl-furan-2-yl), -NHC(O)C(CH₃)₃, -NHC(O)CH₂NHObenzyl, -NHC(O)CH₂NH(3-chlorophenyl), -NHC(O)cyclobutyl, -NHC(O)CH₂(3-methoxyphenyl), -NHC(O)(1-methylcycloprop-1-yl), -NHC(O)(3-flurophenyl), -NHC(O)(4-dimethylaminophenyl), -NHC(O)(3,4-dichlorophenyl), -NHC(O)CH₂NHCH₂(2-methylthiophenyl), -NHC(O)CH₂(2-fluorophenyl), -NHC(O)CH₂N(CH₂CH₃)CH(CH₃)₂, -NHC(O)(thiazol-4-yl), -NHC(O)CH₂N(CH₃)benzyl, -NHC(O)CH₂NHCH₂(thien-2-yl), -NHC(O)CH₂NHCH₂(pyridin-2-yl), -NHC(O)(3-methoxyphenyl), -NHC(O)CH₂NHCH₂(3-chloro-4-methylphenyl), -NHC(O)CH(CH₃)CH₂CH₂CH₃, -NHC(O)CH₂(4-chlorophenyl), -NHC(O)(3-fluoro-4-methylphenyl), -NHC(O)CH₂O(2-methylphenyl), -NHC(O)CH₂(cyclohexyl), -NHC(O)(2-phenyl-cycloprop-1-yl), -NHC(O)(3-chlorophenyl), -NHC(O)CH₂(2-methoxyphenyl), -NHC(O)CH₂CH₂(3-methoxyphenyl), -NHC(O)CH₂NH(2-fluoro-4-methyl-phenyl), -NHC(O)CH₂NHCH₂(3-fluoro-phenyl), -NHC(O)CH₂(4-methoxy-phenyl), -NHC(O)benzyl, -NHC(O)(2,4-dichlorophenyl), -NHC(O)(3-oxo-cyclohex-1-yl), -NHC(O)CH₂NH(3-fluorophenyl), -NHC(O)CH₂(3-chlorophenyl), -NHC(O)CH₂NHCH₂CH(CH₃)phenyl, -NHC(O)CH₂NHCH₂(2,4-dimethylphenyl), -NHC(O)CH₂(2-methyl-piperidin-1-yl), -NHC(O)CH₂NH(2-methoxyphenyl), -NHC(O)CH₂(1,2,3,4-tetrahydroisoquinolin-2-yl), -NHC(O)CH₂CH₂CH=CH₂, -NHC(O)CH₂NH(2-methylphenyl), -NHC(O)CH₂(4-oxo-piperidin-1-yl), -NHC(O)(2-fluorophenyl), -NHC(O)CH₂NHCH(CH₃)phenyl, -NHC(O)(2-fluoro-6-methoxyphenyl), -NHC(O)CH₂NH(2-isopropylphenyl), -NHC(O)CH₂CH₂(2-methoxyphenyl), -NHC(O)CH₂CH₂CH(CH₃)₂, -NHC(O)CH₂(2-phenyl-morpholin-4-yl), -NHC(O)CH₂CH₂(4-methoxyphenyl), -NHC(O)CH₂N(allyl)cyclopentyl, -NHC(O)CH₂N(CH₃)CH₂CH₂OCH₃, -NHC(O)CH₂CH₂C(O)cyclopropyl, -NHC(O)CH₂NH(3-tert-butylphenyl), -NHC(O)CH₂N(n-propyl)(cyclopropylmethyl), -NHC(O)CH₂(2-oxo-cyclopentyl), -NHC(O)CH₂NH(4-chlorophenyl), -NHC(O)CH₂(4-piperidin- 1-ylpiperidin-1-yl), -NHC(O)CH₂(4-cyclopentylpiperazin-1-yl), -NHC(O)CH₂(2-methylphenyl), -NHC(O)CH₂NHCH₂(3-fluoro-6-methylphenyl), -NHC(O)CH₂C(CH₃)₃, -NHC(O)CH₂NH(2-chlorophenyl), -NHC(O)(3-fluoro-6-methylphenyl), -NHC(O)(4-fluoro-3-methylphenyl), -NHC(O)(2,3-dichlorophenyl), -NHC(O)CH₂Ophenyl, -NHC(O)CH₂NH(2,3-dimethylphenyl), -NHC(O)(2-fluoro-5-methylphenyl), -NHC(O)CH₂NHOCH₂(4-methylphenyl), -NHC(O)CH₂(4-isopropylpiperazin-1-yl), -NHC(O)CH₂(4-fluorophenyl), -NHC(O)CH₂CH(CH₃)₂, -NHC(O)(2-methoxy-4-methylphenyl), -NHC(O)CH₂(4-n-propylpiperidin-1-yl), -NHC(O)CH₂O(3-methylphenyl), -NHC(O)(tetrahydrofuran-2-yl), -NHC(O)CH₂(3-hydroxymethylpiperidin-1-yl), -NHC(O)(1-tert-butoxycarbonylpiperidin-2-yl), -NHC(O)CH₂N(CH₃)CH₂(pyridin-3-yl), -NHC(O)CH₂N(CH₂CH₃)phenyl, -NHC(O)CH₂OCH₂CH₂OCH₃, -NHC(O)CH₂CH₂(cyclopentyl), -NHC(O)(2,5-dichlorophenyl), -NHC(O)CH₂(4-methylcarbonylpiperazin-1-yl), -NHC(O)(5-fluoro-2-methoxyphenyl), -NHC(O)CH₂N(CH₂CH₃)cyclohexyl, -NHC(O)(5-methyl-1,2-oxazol-3-yl), -NHC(O)(3-methylpyridin-3-yl), -NHC(O)(2-methoxypyridin-3-yl), -NHC(O)(3,5-dichlorophenyl), -NHC(O)CH₂(thiazolidin3-yl), -NHC(O)CH₂(4-[C(O)H]-piperazin-1-yl), -NHC(O)CH₂(2-pyridin-4-ylpiperidin-1-yl), -NHC(O)(2-methoxyphenyl), -NHC(O)CH₂N(CH₃)CH₂CH(CH₃)₂, -NHC(O)CH₂(4-[C(O)H]-homopiperazin-1-yl), -NHC(O)(1-phenylcycloprop-1-yl), -NHC(O)CH₂(2,6-dimethylmorpholin-4-yl), NHC(O)CH₂(2-phenylpyrrolidin-1-yl), -NHC(O)CH₂(morpholin-4-yl), -C(O)NHCH(CH₃)CH₂N(CH₃)₂, -C(O)NHCH₂CH₂N(CH₃)₂, -C(O)NH(pyrrolidin-3-yl), -C(O)NHCH₂CH₂(pyrrolidin-1-yl), -C(O)NHCH₂CH₂NH₂, -C(O)N(CH₃)CH₂CH₂N(CH₃)₂, -C(O)NHCH₂(piperidin-2-yl), -C(O)NH(1-methylazetidin-3-yl), -C(O)NHCH₂CH₂(piperidin-1-yl), -C(O)NHCH₂CH₂N(CH₂CH₃)₂, -C(O)NH(1-methylpiperidin-3-yl), -C(O)NH(piperidin-3-yl), -C(O)NHCH₂(1-methylpiperidin-3-yl), -C(O)NHCH₂CH₂N(CH₂CH₂OH)₂, -C(O)NH(1-ethylpiperidin-3-yl), -C(O)NH₂, -C(O)(3-aminopyrrolidin-1-yl), -C(O)(3-methylaminopyrrolidin-1-yl), -C(O)OH, -C(O)NHCH₂CH₂(morpholin-4-yl), -C(O)NHCH₂(1-ethylpyrrolidin-2-yl), -C(O)(4-amino-3-oxo-pyrazolidin-1-yl), -C(O)NHCH₃, -C(O)(3-aminocyclobut-1-yl), -C(O)NHCH₂(pyridin-3-yl), -C(O)NHCH₂CH₂OH, -C(O)NH(3-oxo-pyrazolidin-4-yl), -NHCH₂CH₂(imidazol-4-yl), -C(O)(3-dimethylaminopyrrolidin-1-yl), -C(O)NHCH₂(pyridin-4-yl), -C(O)N(CH₃)(1-methyl-pyrrolidin-3-yl), -C(O)(3-diethylaminopyrrolidin-1-yl), -C(O)NH(pyrrol-1-yl), -C(O)NHCH₂CH₂CH₂(pyrrolidin-1-yl), -C(O)N(CH₃)CH₂CH₂CN, -C(O)NHCH₂CH₂OCH₃, -C(O)N(CH₂CH₃)CH₂CH₂CN, -C(O)(3-aminopiperidin-1-yl), -C(O)NHCH₂CH₂CH₂N(CH₃)₂, -C(O)NH(morpholin-4-yl), -C(O)NHN(CH₃)₂, -C(O)NHCH₂CH₂CH₂(imidazol-1-yl), -C(O)NHCH₂CH₂CH₂N(CH₂CH₃)₂, -C(O)NHCH₂CH₂CN, -C(O)NHCH₂CH₂C(O)OCH₃, -C(O)NHCH₂CH₂SCH₃, -C(O)NHCH₂CH₂SCH₂CH₃, -C(O)N(CH₂CH₃)CH₂CH₂N(CH₃)₂, -C(O)NHCH₂CH₂CH₂(2-oxo-pyrrolidin-1-yl), -C(O)NHCH₂CH₂(pyridin-4-yl), -C(O)NHCH₂CH₂CH₂OCH₂CH₃, -C(O)NHCH₂CH₂CH₂(morpholin4-yl), -C(O)NHCH₂CH₂CH₂OCH₃, -C(O)N(CH₃)CH₂CH₂CH₂N(CH₃)₂, -C(O)NHCH₂CH₂CH₂OCH₂CH₂CH₃, -C(O)NHCH₂CH₂C(O)OCH₂CH₃, -C(O)NHCH₂CH₂CH₂OCH(CH₃)₂, -C(O)NHC(CH₃)₂CH₂(piperidin-1-yl), -C(O)N(CH₃)CH₂CH₂CH₃, -C(O)NH(piperidin-1-yl), -C(O)NHCH(CH₃)CH₂OCH₃, -C(O)NHC(CH₃)₂CH₂(morpholin-4-yl), -C(O)(2-dimethylaminomethylpiperidin-1-yl), -C(O)NH(CH₂)₃O(CH₂)₃CH₃, -C(O)NHCH(CH₃)(CH₂)₃N(CH₂CH₃)₂, -C(O)NHC(CH₃)₂C(O)(piperidin-1-yl), -C(O)(4-methylpiperazin-1-yl), -C(O)(2-piperidin-1-ylmethyl-piperidin-1-yl), cyano, -NHCH₃, -CH(CH₃)NHCH₂CH₂N(CH₃)₂, -C(O)CH₃, -S(O)₂NHCH₂CH₂N(CH₃)₂, -S( O)₂NH(CH₂)₃N(CH₃)₂, 5-(N,N-dimethylaminomethyl)-1,3,4-oxadiazol-2-yl, -NHCH₂CH₂N(CH₃)₂, -N(CH₃)₂, -OCH₂CH₂N(CH₃)₂, -NHC[N(CH₃)₂][=N(CH₃)₂], -OCH F₂, -CF₃, -S(O)₂CH₃, -OCF₃, -NHC(O)CH₂(4-dimethylaminopiperidin-1-yl), or methoxy.

[0207] In another (P), the Compound of Formula I is that where each R³ is independently halo, alkyl, hydroxyamino, -N(R⁷)C(O)-C₁-C₆-alkylene-N(R^7a)(R^7b), -C(O)NR⁸R^8a, -NR⁹C(O)R^9a, -C(O)N(R¹⁰)-C₁-C₆-alkylene-N(R^10a)R^10b-NR¹¹C(O)NR^11aR^11b, -N(R²²)C(O)-C₁-C-₆-alkylene-N(R^22b)-N(R^22c)(R^22a), -NR¹³C(O)OR^13a, -N(R¹⁸)C(O)-C₁-C₆-alkylene-N(R^18b)C(O)R^18a, -NR²⁴C(O)-C₁-C₆-alkylene-OR^24a, or -N(R²)C(O)-C₁-C₆-alkylene-C(O)R^20a; where each of the alkylene in R³ is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; and all other groups are as defined above . In another, each R³ is independently methyl, chloro, -NHC(O)CH₂NH(CH₃), -NHC(O)CH(CH₃)NH₂, -NHC(O)C(CH₃)₂NH₂, -NHC(O)CH₂N(CH₃)₂, -NHC(O)CH₂N(CH₃)CH₂CH₂N(CH₃)₂, -NHC(O)CH(NH₂)CH₂CH₃, -NHC(O)CH₂N(CH₃)CH₂CH₂N(CH₃)₂, -NHC(O)CH(CH₃)NH(CH₃), -NHC(O)H, -NHC(O)CH₂(azetidin-1-yl), -NHC(O)(pyrrolidin-2-yl), -NHC(O)CH(NH₂)CH₂OH, -NHC(O)(azetidin-4-yl), -NHC(O)C(CH₃)₂NH(CH₃), -NH₂, -NHC(O)CH₂NH(CH₂CH₂CH₃), -NHC(O)CH₂CH₂NH₂, -NHOH, or -NHC(O)(piperidin-3-yl).

[0208] In another (Q), the Compound of Formula I is that where R³ is alkyl or -N(R⁷)C(O)-C₁-C₆-alkylene-N(R^7a)(R^7b); and R⁷ is hydrogen or alkyl and R^7a and R^7b are independently hydrogen, alkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; and all other groups are as defined above. In another, each R³ is independently methyl, -NHC(O)CH₂NH(CH₃), -NHC(O)CH(CH₃)NH₂, -NHC(O)C(CH₃)₂NH₂, -NHC(O)-CH₂N(CH₃)₂, -NHC(O)CH₂N(CH₃)CH₂CH₂N(CH₃)₂, -NHC(O)CH(NH₂)CH₂CH₃, -NHC(O) CH₂N(CH₃)CH₂CH₂N(CH₃)₂, or -NHC(O)CH(CH₃)NH(CH₃).

[0209] In another (R), the Compound of Formula I is that where B is phenyl, R³ is not present or R³ is halo, alkyl, or alkoxy; R^3a is -C(O)NR⁸R^8a, -NR⁹C(O)R^9a, -N(R⁷)C(O)-C₁-C₆-alkylene-N(R^7a)(R^7b), or -C(O)N(R¹⁰)-C₁-C₆-alkylene-N(R^10a)R^10b where each of the alkylene in R^3a is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; and all other groups are as defined in the Summary of the Invention.

[0210] In another compound (R1) of compound R, the compound is that where R⁵⁰, R⁵², and R⁵³ are hydrogen and R⁵⁴ is halo or alkoxy; R⁵⁰, R⁵², and R⁵⁴ are hydrogen and R⁵³ is alkoxy; or R⁵⁰ and R⁵² are hydrogen and R⁵³ and R⁵⁴ together with the carbons to which they are attached form a 6-membered heteroaryl; and all other groups are as defined above . In another embodiment, R⁵⁰, R⁵², and R⁵³ are hydrogen and R⁵⁴ is halo or alkoxy; or R⁵⁰, R⁵², and R⁵⁴ are hydrogen and R⁵³ is alkoxy.

[0211] In another compound (R2) of compound R, the compound is that where R⁵¹ is methyl.

[0212] In another (S), the compound of Formula Ia:

is that where R³ is not present or R³ is alkyl and R^3a is -N(R⁷)C(O)-C₁-C₆-alkylene-N(R^7a)(R^7b), -C(O)NR⁸R^8a, -NR⁹C(O)R^9a, or -C(O)N(R¹⁰)-C₁-C₆-alkylene-N(R^10a)R^10b; where each of the alkylene in R^3a is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; and all other groups are as defined above . In another, R³ is is not present or is methyl. In another, R³ is is not present.

[0213] Another compound (S1) of compound S is that where R⁷ is hydrogen or alkyl and R^7a, and R^7b are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; R⁸ is hydrogen or alkyl and R^8a is heterocycloalkyl or heterocycloalkylalkyl; R⁹ is hydrogen or alkyl and R^9a is hydrogen, heterocycloalkyl, or heterocycloalkylalkyl; and R¹⁰, R^10a, and R^10b are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl.

[0214] Another compound (S2) of compound S is that where R⁵⁰, R⁵², and R⁵³ are hydrogen and R⁵⁴ is halo or alkoxy; or R⁵⁰, R⁵², and R⁵⁴ are hydrogen and R⁵³ is alkoxy; or R⁵⁰ and R⁵² are hydrogen and R⁵³ and R⁵⁴ together with the carbons to which they are attached form a 6-membered heteroaryl. In another, R⁵⁰, R⁵², and R⁵³ are hydrogen and R⁵⁴ is halo or alkoxy; or R⁵⁰, R⁵², and R⁵⁴ are hydrogen and R⁵³ is alkoxy.

[0215] In another compound of (S3) of compound S, the compound is that where R⁵¹ is methyl.

[0216] In another (T), the Compound of Formula I is that where B is heteroaryl, one R³ is halo, alkyl, or alkoxy and a second R³ is -C(O)NR⁸R^8a, -NR⁹C(O)R^9a, -N(R⁷)C(O)-C₁-C₆-alkylene-N(R^7a)(R^7b), or -C(O)N(R¹⁰)-C₁-C₆-alkylene-N(R^10a)R^10b where each of the alkylene in R³ is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino; and all other groups are as defined above.

[0217] In another compound (T1) of compound T, the compound is that where R⁷ is hydrogen or alkyl and R^7a, and R^7b are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; R⁸ is hydrogen or alkyl and R^8a is heterocycloalkyl or heterocycloalkylalkyl; R⁹ is hydrogen or alkyl and R^9a is hydrogen, heterocycloalkyl, or heterocycloalkylalkyl; R¹⁰, R^10a, and R^10b are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl.

[0218] In another compound U, the compound of Formula I is that where B is

each R³ (when R³ is present) is independently halo, alkyl, alkoxy, aminoalkyloxy, alkylaminoalkyloxy, dialkylaminoalkyloxy, alkylamino, dialkylamino, -C(O)NR⁸R^8a, -NR⁹C(O)R^9a, -N(R⁷)C(O)-C₁-C₆-alkylene-N(R^7a)(R^7b), or -C(O)N(R¹⁰)-C₁-C₆-alkylene-N(R^10a)R^10b; and all other groups are as defined above.

[0219] In another compound (U1) of compound U, the compound of Formula I is that where R⁵⁰, R⁵², and R⁵³ are hydrogen and R⁵⁴ is halo or alkoxy; R⁵⁰, R⁵², and R⁵⁴ are hydrogen and R⁵³ is alkoxy; or R⁵⁰ and R⁵² are hydrogen and R⁵³ and R⁵⁴ together with the carbons to which they are attached form a 6-membered heteroaryl; and all other groups are as defined above. In another embodiment, R⁵⁰, R⁵², and R⁵³ are hydrogen and R⁵⁴ is halo or alkoxy; or R⁵⁰, R⁵², and R⁵⁴ are hydrogen and R⁵³ is alkoxy.

[0220] In another compound (U2) of compound U1, the compound of Formula I is that where R⁵¹ is methyl.

[0221] In another compound (U3) of compound U, the Compound of Formula I is that where R⁷ is hydrogen or alkyl and R^7a, and R^7b are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; R⁸ is hydrogen or alkyl and R^8a is heterocycloalkyl or heterocycloalkylalkyl; R⁹ is hydrogen or alkyl and R^9a is hydrogen, heterocycloalkyl, or heterocycloalkylalkyl; R¹⁰, R^10a, and R^10b are independently hydrogen, alkyl, hydroxyalkyl, aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl

[0222] In another compound (V) the Compound of Formula I is that where W¹, W², W³, and W⁴ are -C(H)=; or W² and W³ are -C(H)= and one of W¹ and W⁴ is -N= and the other is -C(H)=;
R⁵⁰ is hydrogen;
R⁵¹ is hydrogen or alkyl;
R⁵² is hydrogen;
R⁵³ is hydrogen, alkoxy, nitro, amino, or -N(R⁵⁵)C(O)-C₁-C₆-alkylene-N(R^55a)R^55b; and R⁵⁴ is hydrogen, alkyl, alkoxy, or halo; or R⁵³ and R⁵⁴ together with the carbons to which they are attached form a 6-membered heteroaryl;
B is phenyl substituted with R^3a and optionally further substituted with one R³; or
B is heteroaryl optionally substituted with one or two R³;
R^3a is cyano; hydroxyamino; carboxy; alkylsulfonyl, aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; -N(R⁷)C(O)-C₁-C₆-alkylene-N(R^7a)(R^7b); -C(O)NR⁸R^8a; -NR⁹C(O)R^9a; -C(O)N(R¹⁰)-C₁-C₆-alkylene-N(R^10a)R^10b; -NR¹¹C(O)NR¹¹R^11b where R^11a; -C(O)R¹²; -NR¹³C(O)OR^13a; -C(O)N(R¹⁴)N(R^14a)(R¹⁴); -S(O)₂N(R¹⁵)-C₁-C₆-alkylene-N(R^15a)R^15b; -C(O)N(R¹⁶)-C₁-C₆-alkylene-C(O)OR^16a; heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; -N(R¹⁷)-C(=N(R^17b)(R^17a))(NR^17cR^17d); -N(R¹⁸)C(O)-C₁-C₆-alkylene-N(R^18b)C(O)R^18a; -C(O)N(R¹⁹)-C₁-C₆-alkylene-C(O)R^19a; -N(R²²)C(O)-C₁-C₆-alkylene-N(R^22b)-N(R^22c)(R^22a); -C₀-C₆-alkylene-N(R²³)-C₁-C₆-alkylene-N(R^23b)R^23a; or -NR²⁴C(O)-C₁-C₆-alkylene-OR^24a; where each of the alkylene in R^3a is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino;
each R³ (when R³ is present) is independently halo; cyano; alkyl; alkenyl; alkoxy; hydroxyamino; carboxy; alkylsulfonyl, aminoalkyloxy; alkylaminoalkyloxy; dialkylaminoalkyloxy; -N(R⁷)C(O)-C₁-C₆-alkylene-N(R^7a)(R^7b); -C(O)NR⁸R^8a; -NR⁹C(O)R^9a; -C(O)N(R¹⁰)-C₁-C₆-alkylene-N(R^10a)R^10b; -NR¹¹C(O)NR^11aR^11b where R^11a; -C(O)R¹²; -NR¹³C(O)OR^13a; -C(O)N(R¹⁴)N(R^14a)(R^14b); -S(O)₂N(R¹⁵)-C₁-C₆-alkylene-N(R^15a)R^15b; -C(O)N(R¹⁶)-C₁-C₆-alkylene-C(O)OR^16a; heteroaryl optionally substituted with one or two aminoalkyl, alkylaminoalkyl, or dialkylaminoalkyl; -N(R¹⁷)-C(=N(R^17b)R^17a))(NR^17cR^17d); -N(R¹⁸)C(O)-C₁-C₆-alkylene-N(R^18b)C(O)R^18a; -C(O)N(R¹⁹)-C₁-C₆-alkylene-C(O)R^19a; -N(R²²)C(O)-C₁-C₆-alkylene-N(R^22b)-N(R^22c)(R^22a); -C₀-C₆-alkylene-N(R²³)-C₁-C₆-alkylene-N(R^23b)R^23a; or -NR²⁴C(O)-C₁-C₆-alkylene-OR^24a; where each of the alkylene in R³ is independently optionally further substituted with 1, 2, 3, 4, or 5 groups selected from halo, hydroxy, and amino;
provided that when R⁵⁰ and R⁵² are hydrogen, R⁵¹ is hydrogen or methyl, R⁵³ is hydrogen or methoxy, and R⁵⁴ is hydrogen or methoxy, then B is not 2,3-dihydro-1,4-benzodioxinyl, thien-2-yl, or thien-2-yl substituted with one R³ where R³ is halo.

[0223] Another compound (W) is a Compound of Formula I where R⁵⁰, R⁵³, and R⁵⁴ are independently hydrogen, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, hydroxy, alkoxy, alkenyloxy, haloalkoxy, nitro, amino, alkylamino,
dialkylamino, -N(R⁵⁵)C(O)-C₁-C₆-alkylene-N(R^55a)R^55b, alkylcarbonyl, alkenylcarbonyl, carboxy, alkoxycarbonyl, cyano, alkylthio, -S(O)₂NR⁵⁵R^55a, or alkylcarbonylamino and where R⁵⁵ and R^55b are indepedently hydrogen, alkyl, or alkenyl and R^55a is hydrogen, alkyl, alkenyl, hydroxy, or alkoxy; or R⁵³ and R⁵⁴ together with the carbons to which they are attached form a 5- or 6-membered heteroaryl or 5- or 6-membered heterocycloalkyl.

[0224] Another compound (X) is a Compound of Formula I where R⁵³ and R⁵⁴ together with the carbons to which they are attached form a 5- or 6-membered heteroaryl or 5- or 6-membered heterocycloalkyl.

Representative Compounds

[0225] Representative compounds of Formula I and/or II are depicted below. Compounds of Table 1 are named according to systematic application of the nomenclature rules agreed upon by the International Union of Pure and Applied Chemistry (IUPAC), International Union of Biochemistry and Molecular Biology (IUBMB), and the Chemical Abstracts Service (CAS). Names in Table 1 were generated using ACD/Labs naming software 8.00 release, product version 8.08 with the exception of Compound 374 which was named using ChemDraw v. 9.0.1.

Table 1

Representative PI3K-alpha Inhibitors

[0226] The Compounds in Table 1 can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. Salt, solvate, hydrate, and isomer combinations of the Compounds of Claim 1 can be used to practice the invention. In particular, the invention can be practiced with one or two pharmaceutically acceptable salts of a Compound of Claim 1 which salt(s) are formed with one or two acids independently selected from hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid, trifluoroacetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, 3-(4-hydroxybenzoyl)benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, glucoheptonic acid, 4,4'-methylenebis-(3-hydroxy-2-ene-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, p-toluenesulfonic acid, and salicylic acid. In particular, the invention can be practiced with one or two pharmaceutically acceptable salts of a Compound of Claim 1 which salt(s) are formed with one or two bases independently selected from sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline, betaine, ethylenediamine, glucosamine, methylglucamine, theobromine, purines, piperazine, piperidine, N-ethylpiperidine, tromethamine, and N-methylglucamine. Any individual compound (and any optional salt, optional solvate, and optional hydrate thereof) in Table 1 can be used in combination with any of the above embodiments.

[0227] Except compound 357, all the compounds of Table 1 are to be considered as reference examples.

Table 2a.

Representative AKT Inhibitors

[0228] The Compounds in Table 2a can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 2a can be used.

Cmpd No.	Name
1	3-(azetidin-3-ylidenemethyl)-4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
2	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(3-fluoropyridin-4-yl)-1H-pyrazolo[3,4-d]pyrimidine
3	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(3-chloropyridin-4-yl)-1H-pyrazolo[3,4-d]pyrimidine
4	2-({5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylphenyl}oxy)-N,N-dimethylethanamine
5	2-({5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylphenyl}oxy)-N,N-diethylethanamine
6	4-(4-{5-chloro-2-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
7	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-piperazin-1-yl-1H-pyrazolo[3,4-d]pyrimidine
8	N-(3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}prop-2-yn-1-yl)acetamide
9	N,N-diethyl-2-({3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]phenyl}oxy)ethanamine
10	3-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-2-methylphenyl}-N,N-diethylpropan-1-amine
11	3-bromo-4-{4-[5-chloro-2-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
12	3-bromo-4-(4-{5-chloro-2-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
13	2-({3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-2-methylphenyl}oxy)-N,N-diethylethanamine
14	4-[4-(5-chloro-2-methyl-3-{[2-(1-methylpiperidin-4-yl)ethyl]oxy}phenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
15	5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
16	4-(4-{5-chloro-2-methyl-3-[(2-morpholin-4-ylethyl)oxy]phenyl}piperazin-1-yl)-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
17	4-(4-{5-chloro-2-methyl-3-[(2-piperidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
18	3-bromo-4-{4-[5-chloro-2-methyl-3-(3-morpholin-4-ylpropyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
19	3-bromo-4-(4-{5-chloro-2-methyl-3-[3-(4-methylpiperazin-1-yl)propyl]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
20	3-bromo-4-(4-{5-chloro-2-methyl-3-[(2-piperidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
21	3-bromo-4-(4-{5-chloro-2-methyl-3-[(2-morpholin-4-ylethyl)oxy]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
22	4-{4-[5-chloro-2-methyl-3-(3-morpholin-4-ylpropyl)phenyl]piperazin-1-yl}-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
23	N'-{5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylphenyl}-N,N-diethylethane-1,2-diamine
24	4-{4-[5-chloro-2-methyl-3-(3-piperidin-1-ylpropyl)phenyl]piperazin-1-yl}-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
25	4-[4-(5-chloro-3-{[2-(4-ethylpiperazin-1-yl)ethyl]oxy}-2-methylphenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
26	4-(4-{5-chloro-2-methyl-3-[(3-morpholin-4-ylpropyl)oxy]phenyl}piperazin-1-yl)-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
27	3-bromo-4-{4-[5-chloro-2-methyl-3-(3-piperidin-1-ylpropyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
28	N'-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-2-methylphenyl}-N,N-diethylethane-1,2-diamine
29	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
30	4-[4-(5-chloro-2-methyl-3-{[2-(4-methylpiperazin-1-yl)ethyl]oxy}phenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
31	4-[4-(5-chloro-2-methyl-3-{[(1-methylpiperidin-4-yl)methyl]oxy}phenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
32	N,N-diethyl-2-({3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylphenyl}oxy)ethanamine
33	2-[(5-chloro-3-{4-[1-(1,1-dimethylethyl)-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperazin-1-yl}-2-methylphenyl)oxy]-N,N-diethylethanamine
34	2-[(5-chloro-2-methyl-3-{4-[3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperazin-1-yl}phenyl)oxy]-N,N-diethylethanamine
35	4-(4-{5-chloro-2-methyl-3-[(3-pyrrolidin-1-ylpropyl)oxy]phenyl}piperazin-1-yl)-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
36	4-[4-(5-chloro-2-methyl-3-{[3-(4-methylpiperazin-1-yl)propyl]oxy}phenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
37	3-bromo-4-(4-{5-chloro-2-methyl-3-[(3-piperidin-1-ylpropyl)oxy]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
38	3-bromo-4-(4-{5-chloro-2-methyl-3-[(3-morpholin-4-ylpropyl)oxy]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
39	4-(4-{5-chloro-2-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine
40	4-(4-{5-chloro-2-methyl-3-[(3-morpholin-4-ylpropyl)oxy]phenyl}piperazin-1-yl)-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine
41	4-(4-{5-chloro-2-methyl-3-[(2-morpholin-4-ylethyl)oxy]phenyl}piperazin-1-yl)-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine
42	4-(4-{5-chloro-2-methyl-3-[(3-piperidin-1-ylpropyl)oxy]phenyl}piperazin-1-yl)-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
43	4-[4-(5-chloro-3-{[3-(4-ethylpiperazin-1-yl)propyl]oxy}-2-methylphenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
44	5-chloro-2-methyl-3-[4-(1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-(2-pyrrolidin-1-ylethyl)aniline
45	5-chloro-2-methyl-3-[4-(3-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-(2-pyrrolidin-1-ylethyl)aniline
46	N'-(5-chloro-2-methyl-3-{4-[3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperazin-1-yl}phenyl)-N,N-dimethylethane-1,2-diamine
47	3-({5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylphenyl}oxy)-N,N-diethylpropan-1-amine
48	N'-(5-chloro-2-methyl-3-{4-[3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperazin-1-yl}phenyl)-N,N-diethylethane-1,2-diamine
49	5-chloro-2-methyl-N-(2-pyrrolidin-1-ylethyl)-3-{4-[3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperazin-1-yl}aniline
50	3-bromo-4-(4-{4-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
51	4-(4-{4-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
52	3-methyl-4-(4-{4-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
53	4-(4-{5-chloro-2-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
54	4-(4-{5-chloro-2-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-methyl-1H-pyrazolo[3,4-d]pyrimidine
55	4-(4-{5-chloro-2-methyl-3-[(2-piperidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine
56	3-[(5-chloro-2-methyl-3-{4-[3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperazin-1-yl}phenyl)oxy]-N,N-diethylpropan-1-amine
57	5-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
58	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-fluoro-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
59	4-{4-[5-chloro-2-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
60	3-bromo-4-{4-[5-fluoro-2-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
61	4-{4-[5-chloro-2-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine
62	4-(4-{5-chloro-2-methyl-3-[3-(4-methylpiperazin-1-yl)propyl]phenyl}piperazin-1-yl)-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
63	3-bromo-4-(4-pyridin-2-ylpiperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
64	3-bromo-4-[4-(2,4-dimethylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
65	3-bromo-4-{4-[3-(methyloxy)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
66	3-bromo-4-{4-[2-(methyloxy)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
67	3-bromo-4-{4-[4-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
68	4-(4-{5-chloro-2-methyl-3-[(3-pyrrolidin-1-ylpropyl)oxy]phenyl}piperazin-1-yl)-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine
69	4-(4-{5-chloro-2-methyl-3-[(3-piperidin-1-ylpropyl)oxy]phenyl}piperazin-1-yl)-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine
70	4-[4-(5-chloro-2-methyl-3-{[3-(4-methylpiperazin-1-yl)propyl]oxy}phenyl)piperazin-1-yl]-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine
71	4-[4-(5-chloro-3-{[3-(4-ethylpiperazin-1-yl)propyl]oxy}-2-methylphenyl)piperazin-1-yl]-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine
72	3-bromo-4-[4-(5-chloro-2-methyl-3-{[2-(4-methylpiperazin-1-yl)ethyl]oxy}phenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
73	4-[4-(5-chloro-2-methyl-3-{[2-(4-methylpiperazin-1-yl)ethyl]oxy}phenyl)piperazin-1-yl]-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine
74	3-bromo-4-[4-(5-chloro-3-{[2-(4-ethylpiperazin-1-yl)ethyl]oxy}-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
75	3-bromo-4-[4-(3,4-dichlorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
76	3-bromo-4-[4-(3,4-difluorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
77	3-bromo-4-[4-(2,4-dichlorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
78	3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-fluoro-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
79	5-fluoro-2-methyl-N-(2-pyrrolidin-1-ylethyl)-3-{4-[3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperazin-1-yl}aniline
80	4-{4-[3,5-bis(methyloxy)phenyl]piperazin-1-yl}-3-bromo-1H-pyrazolo[3,4-d]pyrimidine
81	4-[4-(5-chloro-3-{[2-(4-ethylpiperazin-1-yl)ethyl]oxy}-2-methylphenyl)piperazin-1-yl]-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine
82	N-{5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylphenyl}-N,N',N'-trimethylethane-1,2-diamine
83	3-({3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-2-methylphenyl}oxy)-N,N-diethylpropan-1-amine
84	3-promo-4-(4-{5-chloro-2-methyl-3-[(3-pyrrolidin-1-ylpropyl)oxy]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
85	3-bromo-4-[4-(5-chloro-2-methyl-3-{[3-(4-methylpiperazin-1-yl)propyl]oxy}phenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
86	3-bromo-4-[4-(5-chloro-3-{[3-(4-ethylpiperazin-1-yl)propyl]oxy}-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
87	3-(5-chloro-2-methyl-3-{4-[3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperazin-1-yl}phenyl)-N,N-diethylpropan-1-amine
88	3-bromo-4-[4-(5-chloro-2-methyl-3-{[(1-methylpiperidin-4-yl)methyl]oxy}phenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
89	3-bromo-4-[4-(5-chloro-2-methyl-3-{[2-(1-methylpiperidin-4-yl)ethyl]oxy}phenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
90	4-[4-(5-chloro-2-methyl-3-{[(1-methylpiperidin-4-yl)methyl]oxy}phenyl)piperazin-1-yl]-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine
91	4-[4-(5-chloro-2-methyl-3-{[2-(1-methylpiperidin-4-yl)ethyl]oxy}phenyl)piperazin-1-yl]-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine
92	4-(4-{5-chloro-2-methyl-3-[3-(4-methylpiperazin-1-yl)propyl]phenyl}piperazin-1-yl)-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine
93	3-bromo-4-[4-(3-chloro-4-fluorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
94	1-{4-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]phenyl}ethanone
95	3-bromo-4-[4-(2,5-dichlorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
96	3-bromo-4-[4-(3,4-dimethylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
97	3-bromo-4-[4-(4-nitrophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
98	3-ethyl-4-(4-phenylpiperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
99	3-ethyl-4-{4-[3-(methyloxy)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
100	4-{4-[5-chloro-2-methyl-3-(3-piperidin-1-ylpropyl)phenyl]piperazin-1-yl}-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine
101	4-[4-(3,6-dimethylpyrazin-2-yl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
102	1-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]isoquinoline
103	3-bromo-4-[4-(2,6-dimethylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
104	3-bromo-4-{4-[4-(ethyloxy)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
105	3-bromo-4-[4-(2-ethylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
106	4-{4-[2,4-bis(methyloxy)phenyl]piperazin-1-yl}-3-bromo-1H-pyrazolo[3,4-d]pyrimidine
107	3-bromo-4-(4-pyrazin-2-ylpiperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
108	3-bromo-4-(4-pyrimidin-2-ylpiperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
109	4-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-(trifluoromethyl)quinoline
110	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]pyrazine-2-carbonitrile
111	4-[4-(4,6-dimethylpyrimidin-2-yl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
112	ethyl 4-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-(trifluoromethyl)pyrimidine-5-carboxylate
113	4-{4-[3-chloro-5-(methyloxy)phenyl]piperazin-1-yl}-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
114	4-[4-(3-bromo-2-chloro-5-fluorophenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
115	2-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]pyridine-3-carboxamide
116	3-ethyl-4-{4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
117	3-bromo-4-{4-[4-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
118	3-bromo-4-{4-[4-(trifluoromethyl)pyrimidin-2-yl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
119	2-({3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]pyrazin-2-yl}oxy)-N,N-dimethylethanamine
120	4-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylquinoline
121	3-bromo-4-[4-(2-nitrophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
122	2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]benzonitrile
123	4-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]benzonitrile
124	3-bromo-4-{4-[4-(trifluoromethyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
125	3-bromo-4-(4-{4-[(phenylmethyl)oxy]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
126	4-{4-[5-chloro-2-methyl-3-(methyloxy)phenyl]piperazin-1-yl}-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
127	2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]pyridine-3-carbonitrile
128	3-bromo-4-[4-(3,5-dichlorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
129	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-chloro-5-fluoro-N-(2-pyrrolidin-1-ylethyl)aniline
130	2-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-fluoro-N-(2-pyrrolidin-1-ylethyl)aniline
131	3-bromo-4-[4-(2,5-difluorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
132	4-[4-(2,5-difluorophenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
133	3-bromo-4-{4-[3-(methyloxy)pyrazin-2-yl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
134	3-bromo-4-[4-(3-chlorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
135	3-bromo-4-{4-[3-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
136	3-bromo-4-{4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
137	4-(4-{5-chloro-2-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-(1-methylethyl)-1H-pyrazolo[3,4-d]pyrimidine
138	5-chloro-2-methyl-3-{4-[3-(1-methylethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperazin-1-yl}-N-(2-pyrrolidin-1-ylethyl)aniline
139	2-({3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]phenyl}oxy)-N-ethylacetamide
140	2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N,N-diethylpyrimidin-4-amine
141	3-bromo-4-[4-(3-{[(3-methylphenyl)methyl]oxy}phenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
142	3-bromo-4-(4-{3-[(2-piperidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
143	3-bromo-4-[4-(4-furan-2-ylpyrimidin-2-yl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
144	6-{2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]pyrimidin-4-yl}-2H-1,4-benzoxazin-3(4H)-one
145	3-ethyl-4-{4-[2-methyl-3-(methyloxy)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
146	N'-{5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylphenyl}-N-methyl-N-(1-methylethyl)ethane-1,2-diamine
147	N'-{5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylphenyl}-N-ethyl-N-methylethane-1,2-diamine
148	N'-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-2-methylphenyl}-N,N-dimethylethane-1,2-diamine
149	3-({6-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-chloro-5-methylpyrimidin-4-yl}oxy)-N,N-diethylpropan-1-amine
150	3-bromo-4-[4-(2,3-dichlorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
151	3-bromo-4-{4-[2-(trifluoromethyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
152	3-bromo-4-(4-phenylpiperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
153	3-bromo-4-[4-(4-fluorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
154	3-bromo-4-[4-(4-chlorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
155	3-bromo-4-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
156	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-amine
157	3-bromo-4-[4-(4-bromophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
158	3-bromo-4-[3-methyl-4-(3-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
159	4-[4-(3-bromo-5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-6-amine
160	4-(4-{5-chloro-2-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-cyclopropyl-1H-pyrazolo[3,4-d]pyrimidine
161	5-chloro-3-[4-(3-cyclopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
162	5-chloro-2-methyl-3-{4-[3-(2-methylpropyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]piperazin-1-yl}-N-(2-pyrrolidin-1-ylethyl)aniline
163	4-(4-{5-chloro-2-methyl-3-[(2-pyrrolidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-(2-methylpropyl)-1H-pyrazolo[3,4-d]pyrimidine
164	3-bromo-4-[(3S)-4-(5-chloro-2-methylphenyl)-3-methylpiperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
165	5-bromo-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylaniline
166	2-({3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]phenyl}oxy)-N-cyclopropylacetamide
167	3-bromo-4-(4-{3-[(2-piperidin-1-ylethyl)oxy]pyrazin-2-yl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
168	4-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-6,7-bis(methyloxy)quinazoline
169	2-({3-chloro-5-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]phenyl}oxy)-N,N-diethylethanamine
170	4-{4-[2-chloro-5-(trifluoromethyl)phenyl]piperazin-1-yl}-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
171	3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-[(2-methylpropyl)oxy]-N-(2-pyrrolidin-1-ylethyl)aniline
172	3-({4-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-6-chloro-5-methylpyrimidin-2-yl}oxy)-N,N-diethylpropan-1-amine
173	3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-[(phenylmethyl)oxy]-N-(2-pyrrolidin-1-ylethyl)aniline
174	3-bromo-4-[(3R)-4-(5-chloro-2-methylphenyl)-3-methylpiperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
175	3-[(2S)-4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2-methylpiperazin-1-yl]-4-methyl-N-phenylbenzamide
176	3-[(2S)-4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2-methylpiperazin-1-yl]-4-methyl-N-(phenylmethyl)benzamide
177	methyl 3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methylbenzoate
178	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methylbenzoic acid
179	(2E)-3-(4-{4-[5-chloro-2-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidin-3-yl)prop-2-enoic acid
180	3-(4-{4-[5-chloro-2-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidin-3-yl)prop-2-yn-1-ol
181	4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1-(5-chloro-2-methylphenyl)piperazin-2-one
182	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-[(2-methylpropyl)oxy]-N-(2-pyrrolidin-1-ylethyl)aniline
183	N'-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-[(2-methylpropyl)oxy]phenyl}-N,N-diethylethane-1,2-diamine
184	methyl 3-bromo-5-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methylbenzoate
185	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-phenylbenzamide
186	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N,4-dimethylbenzamide
187	2-({3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]phenyl}oxy)-N,N-diethylethanamine
188	methyl 3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]benzoate
189	3-bromo-5-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-phenylbenzamide
190	3-bromo-5-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-phenylbenzamide
191	N'-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-2-methylphenyl}-N-methyl-N-(1-methylethyl)ethane-1,2-diamine
192	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-phenyl-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide
193	N'-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-[(2-methylpropyl)oxy]phenyl}-N,N-dimethylethane-1,2-diamine
194	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N,N,4-trimethylbenzamide
195	3-[4-(3-chloro-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-(2-methylpropyl)benzamide
196	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N,N,4-trimethyl-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide
197	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2-oxopiperazin-1-yl]-4-methyl-N-phenylbenzamide
198	3-[(2R)-4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2-(hydroxymethyl)piperazin-1-yl]-4-methyl-N-phenylbenzamide
199	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(pyrrolidin-1-ylcarbonyl)-N-(2-pyrrolidin-1-ylethyl)aniline
200	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N,4-dimethyl-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide
201	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-(4-chlorophenyl)-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide
202	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-(2-chlorophenyl)-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide
203	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(cyclopropylmethyl)oxy]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
204	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-[(3-methylbutyl)oxy]-N-(2-pyrrolidin-1-ylethyl)aniline
205	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(2-ethylbutyl)oxy]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
206	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-(butyloxy)-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
207	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-(1-methylethyl)-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide
208	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N,4-dimethyl-N-(1-methylethyl)-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide
209	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(cyclobutylmethyl)oxy]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
210	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-(ethyloxy)-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
211	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-[2-(dimethylamino)ethyl]-4-methylbenzamide
212	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-(1,1-dimethylethyl)-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide
213	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-pyridin-3-yl-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide
214	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(2-fluoro-2-methylpropyl)oxy]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
215	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(cyclohexylmethyl)oxy]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
216	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(cyclopentylmethyl)oxy]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
217	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-ethyl-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide
218	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-[(1-methylethyl)oxy]-N-(2-pyrrolidin-1-ylethyl)aniline
219	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(2,2-dimethylpropyl)oxy]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
220	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)-5-[(tetrahydrofuran-2-ylmethyl)oxy]aniline
221	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-{[2-(methyloxy)ethyl]oxy}-N-(2-pyrrolidin-1-ylethyl)aniline
222	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(propyloxy)-N-(2-pyrrolidin-1-ylethyl)aniline
223	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-{[2-(dimethylamino)ethyl]amino}-4-methyl-N-phenylbenzamide
224	N'-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(2-fluoro-2-methylpropyl)oxy]-2-methylphenyl}-N,N-dimethylethane-1,2-diamine
225	3-[4-(3-promo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-{[2-(dimethylamino)ethyl]amino}-4-methyl-N-(1-methylethyl)benzamide
226	1-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]phenyl}pentan-1-one
227	N'-(3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-{[2,3-difluoro-2-(fluoromethyl)propyl]oxy}-2-methylphenyl)-N,N-dimethylethane-1,2-diamine
228	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-{[2,3-difluoro-2-(fluoromethyl)propyl]oxy}-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
229	5-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-N-(2-pyrrolidin-1-ylethyl)biphenyl-3-amine
230	1-(3-{5-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methylbiphenyl-3-yl}propyl)pyridinium
231	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)-5-(1,3-thiazol-2-yl)aniline
232	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]benzoic acid
233	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(phenylethynyl)-N-(2-pyrrolidin-1-ylethyl)aniline
234	{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]phenyl}(phenyl)methanone
235	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-ethynyl-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
236	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-(3,3-dimethylbut-1-yn-1-yl)-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
237	3-bromo-4-{4-[5-{[2,3-difluoro-2-(fluoromethyl)propyl]oxy}-2-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
238	3-bromo-4-{4-[2-methyl-5-[(2-methylpropyl)oxy]-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
239	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(3-phenyl-1,2,4-oxadiazol-5-yl)-N-(2-pyrrolidin-1-ylethyl)aniline
240	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(3-methyl-1,2,4-oxadiazol-5-yl)-N-(2-pyrrolidin-1-ylethyl)aniline
241	1-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]phenyl}propan-1-one
242	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-(3,3-dimethylbutyl)-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
243	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-ethyl-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
244	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)-5-[2-(trimethylsilyl)ethyl]aniline
245	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(2-phenylethyl)-N-(2-pyrrolidin-1-ylethyl)aniline
246	1-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]phenyl} butan-1-one
247	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N,4-dimethyl-N-(methyloxy)-5-[(2-pyrrolidin-l-ylethyl)amino]benzamide
248	3-bromo-4-[4-(3-bromo-5-{[2,3-difluoro-2-(fluoromethyl)propyl]oxy}-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
249	4-[4-(3-bromo-5-{[2,3-difluoro-2-(fluoromethyl)propyl]oxy}-2-methylphenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
250	1-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]phenyl}ethanone
251	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(difluoromethyl)oxy]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
252	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-{[(difluoromethyl)oxy]methyl}-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
253	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(methyloxy)-N-(2-pyrrolidin-1-ylethyl)aniline
254	5-{[2,3-difluoro-2-(fluoromethyl)propyl]oxy}-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
255	2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-3,5,6-trifluoro-N-(3-methylbutyl)pyridin-4-amine
256	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-[(cyclopropylmethyl)oxy]-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]benzamide
257	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(5-methyl-1,2,4-oxadiazol-3-yl)-N-(2-pyrrolidin-1-ylethyl)aniline
258	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-(ethylsulfonyl)-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
259	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-5-(methylsulfonyl)-N-(2-pyrrolidin-1-ylethyl)aniline
260	1-{3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]phenyl}pentan-1-one
261	3-bromo-4-[4-(5-{[2,3-difluoro-2-(fluoromethyl)propyl]oxy}-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
262	6-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-3,5-difluoro-N~4~-(3-methylbutyl)-N~2~-(2-pyrrolidin-1-ylethyl)pyridine-2,4-diamine
263	3-bromo-5-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-(2-pyrrolidin-1-ylethyl)aniline
264	3-bromo-4-[4-(3',4',6-trifluoro-4-methylbiphenyl-3-yl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
265	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-chloro-N-(2-pyrrolidin-1-ylethyl)aniline
266	{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]phenyl}methanol
267	3-bromo-4-(4-{4-methyl-2'-[(2-pyrrolidin-1-ylethyl)oxy]biphenyl-3-yl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
268	3-[4-(3-bromo-1H-[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-{[(2,2-difluorocyclopropyl)methyl]oxy}-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
269	5-bromo-3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
270	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(ethyloxy)methyl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
271	3-[4-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-1-methyl-6-(trifluoromethyl)-1H-benzimidazol-2-yl]propan-1-ol
272	1-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]phenyl}-4,4,4-trifluorobutan-1-one
273	{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]phenyl}(cyclopropyl)methanone
274	3-({3'-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4'-methylbiphenyl-2-yl}oxy)-N,N-dimethylpropan-1-amine
275	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-(1,1-difluorobutyl)-2-methyl-N-(2-pyrrolidin-1-ylethyl)aniline
276	3-bromo-4-(4-{4-methyl-2'-[(3-morpholin-4-ylpropyl)oxy]biphenyl-3-yl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
277	3-bromo-4-(4-{4-methyl-2'-[(2-morpholin-4-ylethyl)oxy]biphenyl-3-yl}piperazin-1-yl)-1H pyrazolo[3,4-d]pyrimidine
278	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)-5-{[(2,2,2-trifluoroethyl)oxy]methyl}aniline
279	1-[2-({3'-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4'-methylbiphenyl-2-yl}oxy)ethyl]pyrrolidine-2,5-dione
280	3-bromo-4-(4-{3'-fluoro-4-methyl-2'-[(2-pyrrolidin-1-ylethyl)oxy]biphenyl-3-yl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
281	1-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-[(2-pyrrolidin-1-ylethyl)amino]phenyl}butan-1-one
282	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)-5-[(3,3,3-trifluoropropyl)oxy]aniline
283	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)-5-[(2,2,2-trifluoroethyl)oxy]aniline
284	1-{3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-4-methyl-5-[(2-pyrrolidin-1-ylethyl)amino]phenyl}butan-1-ol
285	3-bromo-4-(4-{4-chloro-2'-[(2-pyrrolidin-1-ylethyl)oxy]biphenyl-3-yl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
286	3-[4-(4-{5-{[2,3-difluoro-2-(fluoromethyl)propyl]oxy}-2-methyl-3-[(2-pyrrolidin-1-ylethyl)amino]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]prop-2-yn-1-ol
287	3-bromo-4-(4-{4-chloro-4'-fluoro-2'-[(2-pyrrolidin-1-ylethyl)oxy]biphenyl-3-yl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
288	3-bromo-4-(4-{4-methyl-3'-[(2-pyrrolidin-1-ylethyl)oxy]biphenyl-3-yl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
289	(2E)-3-[4-(4-{5-{[2,3-difluoro-2-(fluoromethyl)propyl]oxy}-2-methyl-3-[(2-pyrrolidin-1-ylethyl)amino]phenyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]prop-2-enoic acid
290	3-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methyl-N-(2-pyrrolidin-1-ylethyl)-5-[4,4,4-trifluoro-1,1-bis(methyloxy)butyl]aniline
291	6-(4-phenylpiperazin-1-yl)-9H-purine
292	6-[4-(3-chlorophenyl)piperazin-1-yl]-9H-purine
293	4-(4-phenylpiperazin-1-yl)-7H-pyrrolo[2,3-d]pyrimidine
294	4-[4-(3-chlorophenyl)piperazin-1-yl]-7H-pyrrolo[2,3-d]pyrimidine
295	4-(4-phenylpiperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
296	4-[4-(3-chlorophenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
297	6-[4-(2-chlorophenyl)piperazin-1-yl]-9H-purine
298	6-[4-(2-fluorophenyl)piperazin-1-yl]-9H-purine
299	4-[4-(2-methylphenyl)piperazin-1-yl]-7H-pyrrolo[2,3-d]pyrimidine
300	4-{4-[2-(methyloxy)phenyl]piperazin-1-yl}-7H-pyrrolo[2,3-d]pyrimidine
301	4-{4-[3-(methyloxy)phenyl]piperazin-1-yl}-7H-pyrrolo[2,3-d]pyrimidine
302	4-{4-[4-(methyloxy)phenyl]piperazin-1-yl}-7H-pyrrolo[2,3-d]pyrimidine
303	4-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}-7H-pyrrolo[2,3-d]pyrimidine
304	6-{4-[4-(methytoxy)phenyl]piperazin-1-yl}-9H-purine
305	6-{4-[2-(methyloxy)phenyl]piperazin-1-yl}-9H-purine
306	6-[4-(4-chlorophenyl)piperazin-1-yl]-9H-purine
307	6-[4-(4-fluorophenyl)piperazin-1-yl]-9H-purine
308	4-[4-(4-chlorophenyl)piperazin-1-yl]-7H-pyrrolo[2,3-d]pyrimidine
309	4-[4-(2-chlorophenyl)piperazin-1-yl]-7H-pyrrolo[2,3-d]pyrimidine
310	4-[4-(4-fluorophenyl)piperazin-1-yl]-7H-pyrrolo[2,3-d]pyrimidine
311	4-[4-(2-fluorophenyl)piperazin-1-yl]-7H-pyrrolo[2,3-d]pyrimidine
312	6-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}-9H-purine
313	6-[4-(2-methylphenyl)piperazin-1-yl]-9H-purine
314	4-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
315	4-[4-(2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
316	4-[4-(3-chlorophenyl)piperazin-1-yl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidine
317	3-methyl-4-[4-(2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
318	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
319	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-methyl-1H-pyrazolo[3,4-d]pyrimidine
320	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-methyl-6-phenyl-1H-pyrazolo[3,4-d]pyrimidine
321	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
322	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-6-methyl-1H-pyrazolo[3,4-d]pyrimidine
323	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-6-ethyl-1H-pyrazolo[3,4-d]pyrimidine
324	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-6-(1-methylethyl)-1H-pyrazolo[3,4-d]pyrimidine
325	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-phenyl-1H-pyrazolo[3,4-d]pyrimidine
326	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-({[2-(methyloxy)ethyl]oxy}methyl)-1H-pyrazolo[3,4-d]pyrimidine
327	3-bromo-4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
328	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-propyl-1H-pyrazolo[3,4-d]pyrimidine
329	4-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenol
330	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-N-phenyl-1H-pyrazolo[3,4-d]pyrimidin-3-amine
331	4-[4-(3-chlorophenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
332	4- {4-[5-chloro-2-(methyloxy)phenyl]piperazin-1-yl}-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
333	3- {4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenol
334	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-{3-[(phenylmethyl)oxy]phenyl}-1H-pyrazolo[3,4-d]pyrimidine
335	3-(1,3-benzodioxol-5-yl)-4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
336	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(2-thienyl)-1H-pyrazolo[3,4-d]pyrimidine
337	3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}aniline
338	3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}benzoic acid
339	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(4-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidine
340	N-(4-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)acetamide
341	4-[4-(3-chlorophenyl)-1,4-diazepan-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
342	4-[5-(3-chlorophenyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
343	4-(4-{3-chloro-4-[(2-morpholin-4-ylethyl)oxy]phenyl}piperazin-1-yl)-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
344	methyl 1-(3-chlorophenyl)-4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazine-2-carboxylate
345	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(3-methylbut-2-en-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
346	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(trifluoromethyl)-1H-pyrazolo[3,4-d]pyrimidine
347	methyl 4-(3-chlorophenyl)-1-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazine-2-carboxylate
348	4-(4-{3-chloro-4-[(2-piperidin-1-ylethyl)oxy]phenyl}piperazin-1-yl)-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
349	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(1-methylethyl)-1H-pyrazolo[3,4-d]pyrimidine
350	1-(3-chlorophenyl)-4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazine-2-carboxylic acid
351	1-(3-chlorophenyl)-4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-methylpiperazine-2-carboxamide
352	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(phenylmethyl)-1H-pyrazolo[3,4-d]pyrimidine
353	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(2-methylpropyl)-1H-pyrazolo[3,4-d]pyrimidine
354	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-[4-(methyloxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidine
355	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(4-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidine
356	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-[4-(phenyloxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidine
357	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-{4-[(piperidin-4-ylmethyl)oxy]phenyl}-1H-pyrazolo[3,4-d]pyrimidine
358	1-(3-chlorophenyl)-N-[2-(dimethylamino)ethyl]-4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazine-2-carboxamide
359	4-[4-(5-chloro-2-methyl-3-morpholin-4-ylphenyl)piperazin-1-yl]-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
360	4-(3-chlorophenyl)-1-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-methylpiperazine-2-carboxamide
361	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-[2-(methyloxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidine
362	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-pyridin-4-yl-1H-pyrazolo[3,4-d]pyrimidine
363	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-[3-(methyloxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidine
364	4-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}benzonitrile
365	[5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-(methyloxy)phenyl]methanol
366	methyl 5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-(methyloxy)benzoate
367	(2E)-3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}prop-2-enoic acid
368	3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}propanoic acid
369	3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}propan-1-ol
370	methyl (2E)-3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}prop-2-enoate
371	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-{4-[(2-morpholin-4-ylethyl)oxy]phenyl}-1H-pyrazolo[3,4-d]pyrimidine
372	5-chloro-N-[2-(dimethylamino)ethyl]-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-(methyloxy)benzamide
373	4-(4-{5-chloro-2-(methyloxy)-3-[(4-methylpiperazin-1-yl)carbonyl]phenyl}piperazin-1-yl)-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
374	2-(dimethylamino)ethyl 5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-(methyloxy)benzoate
375	1-[5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-(methyloxy)phenyl]-N,N-dimethylmethanamine
376	N'-{[5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-(methyloxy)phenyl]methyl}-N,N-dimethylethane-1,2-diamine
377	[1-(3-chlorophenyl)-4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-2-yl]methanol
378	3-[(4-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenyl)oxy]-N,N-dimethylpropan-1-amine
379	2-chloro-4-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-methylphenol
380	1-(3-chlorophenyl)-4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-(1-methylpiperidin-4-yl)piperazine-2-carboxamide
381	1-(3-chlorophenyl)-4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-(2-morpholin-4-ylethyl)piperazine-2-carboxamide
382	2- {[5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-(methyloxy)phenyl]oxy}-N,N-dimethylethanamine
383	3- {5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylphenyl}-N,N-dimethylprop-2-yn-1-amine
384	N'-{5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylphenyl}-N,N-dimethylethane-1,2-diamine
385	1,1-dimethylethyl (2E)-3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}prop-2-enoate
386	3-({2-chloro-4-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-methylphenyl}oxy)-N,N-dimethylpropan-1-amine
387	2-({2-chloro-4-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-5-methylphenyl}oxy)-N,N-dimethylethanamine
388	4- {4-[5-chloro-2-methyl-4-(methyloxy)phenyl]piperazin-1-yl}-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine
389	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(4-methylpiperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
390	3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-N,N-diethylprop-2-yn-1-amine
391	3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}prop-2-yn-1-ol
392	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(piperidin-4-ylmethyl)-1H-pyrazolo[3,4-d]pyrimidine
393	phenylmethyl (3aR,6aS)-5-({4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}methylidene)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate
394	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-[(E)-(3aR,6aS)-hexahydrocyclopenta[c]pyrrol-5(1H)-ylidenemethyl]-1H-pyrazolo[3,4-d]pyrimidine
395	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(3-pyrrolidin-1-ylprop-1-yn-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
396	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-[3-(4-methylpiperazin-1-yl)prop-1-yn-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
397	3-{4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-N,N-diethylpropan-1-amine
398	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(3-pyrrolidin-1-ylpropyl)-1H-pyrazolo[3,4-d]pyrimidine
399	4-[4-(5-chloro-2-methylphenyl)piperazin-1-yl]-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrazolo[3,4-d]pyrimidine
400	3-{5-chloro-3-[4-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-methylphenyl}-N,N-diethylpropan-1-amine
401	4-{4-[5-chloro-2-methyl-3-(3-pyrrolidin-1-ylpropyl)phenyl]piperazin-1-yl}-3-ethyl-1H-pyrazolo[3,4-d]pyrimidine

Table 2b.

Additional Representative AKT Inhibitors

[0229] The Compounds in Table 2b can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 2b can be used.

Entry	Name
1	[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-chlorophenyl)methanol
2	2-{[[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-chlorophenyl)methyl]oxy}-N,N-dimethylethanamine
3	3-{[[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-chlorophenyl)methyl]oxy}-N,N-dimethylpropan-1-amine
4	3-bromo-4-{4-[(4-bromophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
5	{4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1-[(4-chlorophenyl)methyl]piperazin-2-yl}methanol
6	N'-[[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-chlorophenyl)methyl]-N,N-diethylethane-1,2-diamine
7	3-bromo-4-(4-{[4-(1,1-dimethylethyl)phenyl]methyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
8	4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1-[(4-chlorophenyl)methyl]piperazin-2-one
9	2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-2-(4-chlorophenyl)-N-[2-(dimethylamino)ethyl]acetamide
10	N-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-N-(4-chlorophenyl)-N,N'-diethylpropane-1,3-diamine
11	3-bromo-4-(4-{[4-(trifluoromethyl)phenyl]methyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
12	N-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-N-(4-chlorophenyl)-N'-[2-(dimethylamino)ethyl]urea
13	N-[[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-chlorophenyl)methyl]-N'-[2-(dimethylamino)ethyl]urea
14	2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-2-oxopiperazin-1-yl]-2-(4-chlorophenyl)-N-[2-(dimethylamino)ethyl]acetamide
15	2-(dimethylamino)ethyl[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-chlorophenyl)carbamate
16	3-bromo-4-{4-[(4-chloro-3-fluorophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
17	3-bromo-4-{4-[(4-chloro-2-fluorophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
18	N-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-N-(4-chlorophenyl)-N',N-diethylethane-1,2-diamine
19	3-bromo-4-{4-[(4-chlorophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
20	[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-fluorophenyl)methanone
21	N-[[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-chlorophenyl)methyl]-N',N-diethyl-N-methylethane-1,2-diamine
22	[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-fluorophenyl)methanol
23	3-bromo-4-(4-{[2-fluoro-4-(trifluoromethyl)phenyl]methyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
24	N-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-N-(4-chlorophenyl)-N∼3∼,N∼3∼-diethyl-beta-alaninamide
25	2-{[[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-fluorophenyl)methyl]oxy}-N,N-dimethylethanamine
26	N-[[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-chlorophenyl)methyl]-N∼3∼,N∼3∼-diethyl-beta-alaninamide
27	3-bromo-4-{4-[(3,4-dichlorophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
28	N-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-N-(4-chlorophenyl)-N'-(2-(dimethylamino)ethyl)ethanediamide
29	N-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-N-(4-chlorophenyl)-2-(diethylamino)ethanesulfonamide
30	4-[4-(biphenyl-4-ylmethyl)piperazin-1-yl]-3-bromo-1H-pyrazolo[3,4-d]pyrimidine
31	3-bromo-4-{(3S)-4-[(4-chlorophenyl)methyl]-3-methylpiperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
32	3-bromo-4-(4-{[4-(methyloxy)phenyl]methyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
33	4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-[3-(trifluoromethyl)phenyl]piperazine-1-carboxamide
34	3-bromo-4-{4-[(4-fluorophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
35	N-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-N-(4-chlorophenyl)pent-4-enamide
36	3-bromo-4-[4-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
37	4-[4-(1,3-benzodioxol-5-ylmethyl)piperazin-1-yl]-3-bromo-1H-pyrazolo[3,4-d]pyrimidine
38	[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-chlorophenyl)methanone
39	3-bromo-4-(4-{[4-(phenyloxy)phenyl]methyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
40	3-brorno-4-{4-[(3,4-dichlorophenyl)methyl]piperidin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
41	4-{[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]methyl}-N,N-dimethylaniline
42	methyl 4-{[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]methyl}benzoate
43	3-bromo-4-{4-[(2E)-3-phenylprop-2-enoyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
44	1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-4-[(4-chlorophenyl)methyl]-N-[3-(diethylamino)propyl]piperidine-4-carboxamide
45	3-bromo-4-{4-[(2-bromophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
46	3-bromo-4-{4-[(2-chlorophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
47	3-bromo-4-{4-[(2,4-dichlorophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
48	3-bromo-4-{4-[(2-chloro-4-fluorophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
49	1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-4-(4-chlorophenyl)-N-[3-(diethylamino)propyl]piperidine-4-carboxamide
50	3-bromo-4-[4-(phenylmethyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
51	2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N-pyridin-2-ylacetamide
52	3-bromo-4-[4-(1H-imidazol-2-ylmethyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
53	3-bromo-4-(4-{[3-(phenyloxy)phenyl]methyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
54	3-bromo-4-{4-[(3-methylphenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
55	3-{[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]methyl}benzonitrile
56	3-bromo-4-{4-[(2-chloro-6-fluorophenyl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
57	3-bromo-4-[4-(1-phenylethyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
58	3-bromo-4-[4-(pyridin-4-ylmethyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
59	1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-N-(4-chlorophenyl)piperidin-4-amine
60	3-bromo-4-[4-(pyridin-3-ylmethyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
61	3-bromo-4-(4-{[2,3,4-tris(methyloxy)phenyl]methyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
62	3-bromo-4-[4-({3-[(phenylmethyl)oxy]phenyl}methyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
63	3-bromo-4-[4-(naphthalen-1-ylmethyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
64	3-bromo-4-(4-{[5-(4-chlorophenyl)furan-2-yl]methyl}piperazin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
65	3-bromo-4-[4-({4-[(4-fluorophenyl)oxy]-3-nitrophenyl}methyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
66	3-bromo-4-[4-(furan-2-ylcarbonyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
67	3-bromo-4-[4-(1H-indol-6-ylcarbonyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
68	3-bromo-4-{4-[2-(2-thienyl)ethyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
69	3-bromo-4-[4-(3-pyrrolidin-1-ylpropyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
70	3-bromo-4-[4-(cyclohexylmethyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
71	3-bromo-4-{4-[(10-chloroanthracen-9-yl)methyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
72	3-bromo-4-[4-(1-methylpropyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
73	4-(4-{[4,6-bis(methyloxy)pyrimidin-2-yl]methyl}piperazin-1-yl)-3-bromo-1H-pyrazolo[3,4-d]pyrimidine
74	3-bromo-4-{4-[2-(methyloxy)ethyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
75	3-bromo-4-[4-(2-morpholin-4-yl-2-oxoethyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
76	3-bromo-4-{4-[3-(methyloxy)propyl]piperazin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
77	4-{4-[[4,6-bis(methyloxy)pyrimidin-2-yl](phenyl)methyl]piperazin-1-yl}-3-bromo-1H-pyrazolo[3,4-d]pyrimidine
78	3-bromo-4-[4-(6,7,8,9-tetrahydro-5H-benzocyclohepten-5-yl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
79	3-bromo-4-[4-({4-[(phenylmethyl)oxy]phenyl}methyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
80	3-bromo-4-[4-({3-chloro-4-[(phenylmethyl)oxy]phenyl}methyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
81	4-{[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]methyl}-N-(3-morpholin-4-ylpropyl)benzamide
82	4-{[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]methyl}-N-[3-(methyloxy)propyl]benzamide
83	2-[({4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-1-[(4-chlorophenyl)methyl]piperazin-2-yl}methyl)oxy]-N,N-dimethylethanamine
84	3-bromo-4-[4-({4-[(4-chlorophenyl)oxy]-3-nitrophenyl}methyl)piperazin-1-yl]-1H-pyrazolo[3,4-d]pyrimidine
85	2-[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl]-N,N-dimethylacetamide
86	2-{[(R)-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-chlorophenyl)methyl]oxy}-N,N-dimethylethanamine
87	N-(4-bromo-3-fluorophenyl)-N-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-N'-[2-(dimethylamino)ethyl]urea
88	2-({(R)-(4-chlorophenyl)[1-(3-ethyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]methyl}oxy)-N,N-dimethylethanamine
89	2-{[(S)-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)pipendin-4-yl](4-chlorophenyl)methyl]oxy}-N,N-dimethylethanamine
90	3-bromo-4-(4-{(R)-(4-chlorophenyl)[(2-pyrrolidin-1-ylethyl)oxy]methyl}piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
91	1-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-1-(4-chlorophenyl)-4-(dimethylamino)butan-1-ol
92	2-{[(R)-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-chloro-3-fluorophenyl)methyl]oxy}-N,N-dimethylethanamine
93	3-bromo-4-(4-{(R)-(4-chlorophenyl)[(2-piperidin-1-ylethyl)oxy]methyl}piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
94	4-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-4-(4-chlorophenyl)-N,N-dimethylbutan-1-amine
95	3-bromo-4-(4-{(R)-(4-chlorophenyl)[(2-morpholin-4-ylethyl)oxy]methyl}piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
96	1-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-1-(4-fluorophenyl)-N-(furan-2-ylmethyl)-N-methylmethanamine
97	1-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]-1-(4-fluorophenyl)-N-methyl-N-(pyridin-2-ylmethyl)methanamine
98	4-{[{[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-fluorophenyl)methyl}(methyl)amino]methyl}-N,N-dimethylaniline
99	[4-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperazin-1-yl](1H-indol-6-yl)methanol
100	3-bromo-4-(4-{(R)-(4-chloro-3-fluorophenyl)[(2-pyrrolidin-1-ylethyl)oxy]methyl}piperidin-1-yl)-1H-pyrazolo[3,4-d]pyrimidine
101	3-bromo-4-{4-[(4-chlorophenyl)oxy]piperidin-1-yl}-1H-pyrazolo[3,4-d]pyrimidine
102	2-{[(R)-[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl](4-chlorophenyl)methyl]oxy}-N,N-diethylethanamine
103	2-{[1-(3-bromo-1H-pyrazolo[3,4-d]pyrimidin-4-yl)piperidin-4-yl]oxy}-5-chloro-N-(2-pyrrolidin-1-ylethyl)aniline

Table 3a.

Representative c-MET and/or Flt-3 Inhibitors

[0230] The Compounds in Table 3a can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 3a can be used.

Cmpd No.	Name
1	N-(4-fluorophenyl)-N'-[3-fluoro-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenyl]propanediamide
2	N-(4-fluorophenyl)-N'-[3-fluoro-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenyl]cyclopropane-1,1-dicarboxamide
3	N-({[3-fluoro-4-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)phenyl]amino}carbonothioyl)-2-phenylacetamide
4	N-(4-fluorophenyl)-N'-(4-{[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxy}phenyl)cyclopropane-1,1-dicarboxamide
5	2-phenyl-N-{[(4-{[1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]oxy}phenyl)amino]carbonothioyl}acetamide
6	N-(4-fluorophenyl)-N'-[4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl]cyclopropane-1,1-dicarboxamide
7	2-phenyl-N-({[4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl]amino}carbonothioyl)acetamide
8	N-(4-fluorophenyl)-N'-(4-{[9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl]oxy}phenyl)cyclopropane-1,1-dicarboxamide
9	2-phenyl-N-{[(4-{[9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl]oxy)phenyl)amino]carbonothioyl}acetamide
10	N-(4-fluorophenyl)-N'-[4-(9H-purin-6-yloxy)phenyl]cyclopropane-1,1-dicarboxamide
11	2-phenyl-N-({[4-(9H-purin-6-yloxy)phenyl]amino}carbonothioyl)acetamide
12	N-{3-fluoro-4-[(6-{[(2-morpholin-4-ylethyl)amino]carbonyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Table 3b.

Additional Representative c-MET, c-KIT, and/or Flt-3 Inhibitors

[0231] The Compounds in Table 3b can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 3b can be used.

Entry	Name
1	N-[({3-fluoro-4-[(6-(methyloxy)-7-{[(3aR,6aS)-octahydrocyclopenta[c]pyrrol-5-ylmethyl]oxy}quinazolin-4-yl)oxy]phenyl}amino)carbonothioyl]-2-phenylacetamide
2	N-{[(3-fluoro-4-{[7-({[(3aR,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-yl]oxy}phenyl)amino]carbonothioyl}-2-phenylacetamide
3	N-{[(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)(methyl)amino]carbonothioyl}-2-phenylacetamide
4	1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)imidazolidin-2-one
5	1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-3-(phenylmethyl)imidazolidin-2-one
6	1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-3-(phenylacetyl)imidazolidin-2-one
7	ethyl [(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)amino](oxo)acetate
8	N-{[(4-{[6,7-bis(methyloxy)quinazolin-4-yl]amino}-3-fluorophenyl)amino]carbonothioyl}-2-phenylacetamide
9	N'-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N-methyl-N-(2-phenylethyl)sulfamide
10	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-3-(phenylmethyl)-1,2,4-oxadiazol-5-amine
11	1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)piperidin-2-one
12	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(phenylmethyl)ethanediamide
13	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-4-phenyl-1,3-thiazol-2-amine
14	N-(4- {[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(2-phenylethyl)ethanediamide
15	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-1-phenylmethanesulfonamide
16	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-2-phenylethanesulfonamide
17	4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluoro-N-(phenylmethyl)benzenesulfonamide
18	4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluoro-N-methyl-N (phenylmethyl)benzenesulfonamide
19	4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluoro-N-(2-phenylethyl)benzenesulfonamide
20	4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluoro-N-methyl-N-(2-phenylethyl)benzenesulfonamide
21	4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluoro-N-(3-phenylpropyl)benzenesulfonamide
22	1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)pyrrolidin-2-one
23	4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl(phenylmethyl)carbamate
24	4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl(2-phenylethyl)carbamate
25	4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluoro-N-methyl-N-(3-phenylpropyl)benzenesulfonamide
26	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-phenylethanediamide
27	N-{[(3-fluoro-4-{[7-{[(2-methyloctahydrocyclopenta[c]pyrrol-5-yl)methyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}phenyl)amino]carbonothioyl}-2-phenylacetamide
28	N-[(Z)-[(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)amino](imino)methyl]-2-phenylacetamide
29	4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluoro-N-[2-(phenyloxy)ethyl]benzenesulfonamide
30	N,N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-bis-(3-phenylpropane-1-sulfonamide)
31	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-3-phenylpronane-1-sulfonamide
32	N2-[(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)sulfonyl]-N1-phenylglycinamide
33	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridin-3-yl)-2-phenylacetamide
34	N-{[(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridin-3-yl)amino]carbonothioyl}-2-phenylacetamide
35	6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-1,3-benzothiazol-2-amine
36	6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-1,3-benzothiazol-2-amine
37	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-1,3-benzothiazol-2-yl)-2-phenylacetamide
38	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(2-morpholin-4-ylethyl)ethanediamide
39	benzyl- {[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenylcarbamoyl]-methyl}-carbamic acid tert-butyl ester
40	N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'2-(phenylmethyl)glycinamide
41	N2-acetyl-N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-(phenylmethyl)glycinamide
42	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-1,3-benzothiazol-2-yl)-2-phenylacetamide
43	benzyl-{[6-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-3-ylcarbamoyl]-methyl}-carbamic acid tert-butyl ester
44	N1-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridin-3-yl)-N2-(phenylmethyl)glycinamide
45	N2-acetyl-N1-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridin-3-yl)-N2-(phenylmethyl)glycinamide
46	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridin-3-yl)-3-phenylpropanamide
47	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridin-3-yl)-4-phenylbutanamide
48	N1-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridin-3-yl)-N2-methyl-N2-(phenylmethyl)glycinamide
49	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-{2-[4-(methyloxy)phenyl]ethyl}ethanediamide
50	N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-methyl-N2-(phenylmethyl)glycinamide
51	4-[(2-amino-1,3-benzothiazol-6-yl)oxy]-6,7-bis(methyloxy)-1-(2-oxo-2-phenylethyl)quinolinium
52	N-{[(4-{[6,7-bis(methyloxy)quinolin-4-yl]amino}phenyl)amino]carbonothioyl}-2-phenylacetamide
53	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-1,3-benzothiazol-2-yl)-3-phenylpropanamide
54	N-{[(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)amino]carbonothioyl}-2-phenylacetamide
55	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(2,3-dihydro-1H-inden-1-yl)ethanediamide
56	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(2,3-dihydro-1H-inden-2-yl)ethanediamide
57	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(1,2,3,4-tetrahydronaphthalen-1-yl)ethanediamide
58	N'-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N-(2-phenylethyl)-N-(phenylmethyl)sulfamide
59	N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'2-(trifluoroacetyl)glycinamide
60	N-{[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluoro-phenylcarbamoyl]-methyl}-benzamide
61	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridin-3-yl)-N'-(4-fluorophenyl)propanediamide
62	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-[(2S)-1,2,3,4-tetrahydronaphthalen-2-yl]ethanediamide
63	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-[2-(4-methylphenyl)ethyl]ethanediamide
64	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(2-phenylpropyl)ethanediamide
65	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-[2-(4-chlorophenyl)ethyl]ethanediamide
66	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N,N'-bis(phenylmethyl)sulfamide
67	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N,N'-bis(2-phenylethyl)sulfamide
68	ethyl [(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)amino](oxo)acetate
69	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N'-(2-phenylethyl)ethanediamide
70	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N'-(4-fluorophenyl)propanediamide
71	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(1,2,3,4-tetrahydronaphthalen-2-yl)ethanediamide
72	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-[2-(1-methylpyrrolidin-2-yl)ethyl]ethanediamide
73	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-[2-(phenyloxy)ethyl]ethanediamide
74	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-[2-hydroxy-1-(phenylmethyl)ethyl]urea
75	1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-3-[(4-methylphenyl)sulfonyl]-4-(phenylmethyl)imidazolidin-2-one
76	N'-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N-methyl-N-(2-phenylethyl)ethanediamide
77	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-{[3-(trifluoromethyl)phenyl]methyl}ethanediamide
78	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-{2-[3-(trifluoromethyl)phenyl]ethyl} ethanediamide
79	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-3-oxo-4-phenylbutanamide
80	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-2-[3-(trifluoromethyl)phenyl]acetamide
81	6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-N-[2-(phenyloxy)ethyl]-1,3-benzothiazol-2-amine
82	6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-N-(2-piperidin-1-ylethyl)-1,3-benzothiazol-2-amine
83	6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-N-methyl-N-(2-phenylethyl)-1,3-benzothiazol-2-amine
84	6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-N-(2-pyrrolidin-1-ylethyl)-1,3-benzothiazol-2-amine
85	6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-N-{[3-(trifluoromethyl)phenyl]methyl}-1,3-benzothiazol-2-amine
86	6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-N-{2-[3-(trifluoromethyl)phenyl]ethyl}-1,3-benzothiazol-2-amine
87	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N'-[3-(trifluoromethyl)phenyl]propanediamide
88	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-1,3-benzothiazol-2-yl)-2-[3-(trifluoromethyl)phenyl]acetamide
89	N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-{[3-(trifluoromethyl)phenyl]methyl}glycinamide
90	N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-(2-phenylethyl)glycinamide
91	N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-{2-[3-(trifluoromethyl)phenyl]ethyl}glycinamide
92	benzyl-{[5-chloro-6-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-3-ylcarbamoyl]-methyl}-carbamic acid tert-butyl ester
93	N1-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N2-(phenylmethyl)glycinamide
94	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-1,3-benzothiazol-2-yl)-2-[3,5-bis(trifluoromethyl)phenyl]acetamide
95	N-(6- {[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-1,3-benzothiazol-2-yl)-2-[2-chloro-5-(trifluoromethyl)phenyl]acetamide
96	N-{3-fluoro-4-[(6-(methyloxy)-7-{[(1-methylpiperidin-4-yl)methyl]oxy}quinolin-4-yl)oxy]phenyl}-N'-(2-phenylethyl)ethanediamide
97	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(1,2,3,4-tetrahydroisoquinolin-1-ylmethyl)ethanediamide
98	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-[(2-methyl-1,2,3,4-tetrahydroisoquinolin-1-yl)methyl]ethanediamide
99	N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-methyl-N2-{[3-(trifluoromethyl)phenyl]methyl}glycinamide
100	N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-methyl-N2-{2-[3-(trifluoromethyl)phenyl]ethyl}glycinamide
101	N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N2-methyl-N2-(2-phenylethyl)glycinamide
102	1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-4-(phenylmethyl)imidazolidin-2-one
103	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}pyridazin-3-yl)-N'-(4-fluorophenyl)propanediamide
104	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N'-(2-chlorophenyl)propanediamide
105	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N'-(3-chlorophenyl)propanediamide
106	N1-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N2-methyl-N2-(phenylmethyl)glycinamide
107	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N'-(4-chlorophenyl)propanediamide
108	(2E)-N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-2-[(methyloxy)imino]propanamide
109	(2E)-N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-2-[(ethyloxy)imino]propanamide
110	(2E)-N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-2-{[(phenylmethyl)oxy]imino}propanamide
111	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-1-(phenylmethyl)prolinamide
112	1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-3-[(4-methylphenyl)sulfonyl]-4-(phenylmethyl)imidazolidin-2-one
113	1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-4-(phenylmethyl)imidazolidin-2-one
114	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-4-(phenylmethyl)-4,5-dihydro-1,3-oxazol-2-amine
115	6,7-bis(methyloxy)-4-({4-[4-(phenylmethyl)piperazin-1-yl]phenyl}oxy)quinoline
116	1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-4-(phenylmethyl)piperazin-2-one
117	N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N2-(phenylmethyl)alaninamide
118	N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N2-methyl-N2-(phenylmethyl)alaninamide
119	N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N2-(phenylmethyl)leucinamide
120	N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N2-methyl-N2-(phenylmethyl)leucinamide
121	N1-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N2-(phenylmethyl)valinamide
122	4-(6,7-dimethoxy-quinolin-4-ylamino)-N-(3-phenyl-propyl)-benzamide
123	4-benzyl-1-[4-(6,7-dimethoxy-quinolin-4-yloxy)-phenyl]-tetrahydro-pyrimidin-2-one
124	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-phenethyl-oxalamide
125	2-(Benzyl-methyl-amino)-N-[4-(6,7-dimethoxy-quinolin-4-yloxy)-phenyl]-3-methyl-butyramide (note: Alphabetic order of prefixes ignored while selecting parent chain)
126	N-[4-(6,7-Dimethoxy-quinolin-4-yloxy)-phenyl]-2-phenoxyimino-propionamide
127	2-Benzyloxyimino-N-[4-(6,7-dimethoxy-quinolin-4-yloxy)-phenyl]-2-phenyl-acetamide
128	4-[4-(4-Benzyl-piperidin-1-yl)-phenoxy]-6,7-dimethoxy-quinoline
129	N-[4-(6,7-Dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-N'-(2-isopropyl-1,2,3,4-tetrahydro-isoquinolin-1-ylmethyl)-oxalamide
130	N-[4-(6,7-Dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-N'-(2-ethyl-1,2,3,4-tetrahydro-isoquinolin-1-ylmethyl)-oxalamide
131	4-(4-{3-Chloro-5-[2-(4-fluoro-phenylcarbamoyl)-acetylamino]-pyridin-2-yloxy}-6-methoxy-quinolin-7-yloxymethyl)-piperidine-1-carboxylic acid tert-butyl ester
132	N-{5-Chloro-6-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-pyridin-3-yl}-N'-(4-fluoro-phenyl)-malonamide
133	N-{5-Chloro-6-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-4-yloxy]-pyridin-3-yl}-N'-(4-fluoro-phenyl)-malonamide
134	N-{4-[7-(3-Diethylamino-propoxy)-6-methoxy-quinolin-4-yloxy]-3-fluorophenyl}-N'-phenethyl-oxalamide
135	N-{3-Fluoro-4-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-yloxy]-phenyl}-N'-phenethyl-oxalamide
136	N-{3-Fluoro-4-[6-methoxy-7-(3-piperidin-1-yl-propoxy)-quinolin-4-yloxyl-phenyl}-N'-phenethyl-oxalamide
137	N-{4-[7-(2-Diethylamino-ethoxy)-6-methoxy-quinolin-4-yloxy]-3-fluoro-phenyl}-N'-phenethyl-oxalamide
138	N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-methyl-N'-phenethyl-oxalamide
139	N-{3-Fluoro-4-[6-methoxy-7-(2-methyl-octahydro-cyclopenta[c]pyrrol-5-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-phenethyl-oxalamide
140	N-{3-Fluoro-4-[6-methoxy-7-(2-methyl-octahydro-cyclopenta[c]pyrrol-5-ylmethoxy)-quinazolin-4-yloxy]-phenyl}-N'-phenethyl-oxalamide
141	2-(3,4-Dihydro-1H-isoquinolin-2-yl)-N-{3-fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-2-oxo-acetamide
142	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-2-oxo-2-(3-phenyl-pyrrolidin-1-yl)-acetamide
143	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-2-oxo-2-(2-phenyl-morpholin-4-yl)-acetamide
144	N-(2-Dimethylamino-2-phenyl-ethyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
145	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-oxo-2-phenyl-ethyl)-oxalamide
146	N-[5-Chloro-6-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-3-yl]-2,2-difluoro-N'-(4-fluoro-phenyl)-malonamide
147	N-Benzyl-N'-{3-fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
148	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-[2-(2-fluoro-phenyl)-ethyl]-oxalamide
149	N-[2-(3-Chloro-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
150	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-[2-(2-methoxy-phenyl)-ethyl]-oxalamide
151	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-pyridin-3-yl-ethyl)-oxalamide
152	N-Benzyl-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
153	N-[2-(2,5-Dimethoxy-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
154	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl)-N'-[2-(2-trifluoromethyl-phenyl)-ethyl]-oxalamide
155	N-[2-(2-Ethoxy-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
156	N-[2-(2,4-Dimethyl-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxyl]-phenyl}-oxalamide
157	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(1S-phenyl-2-p-tolyl-ethyl)-oxalamide
158	N-[2-(4-Chloro-phenyl-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
159	N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamic acid
160	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-[2-(3-fluoro-phenyl)-ethyl]-oxalamide
161	N-[2-(2-Chloro-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
162	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl)-N'-[2-(3-methoxy-phenyl)-ethyl]-oxalamide
163	N-(1,2-Diphenyl-ethyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
164	N-[2-(2,4-Dichloro-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
165	N-[2-(3,4-Dimethoxy-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
166	N-[2-(4-Ethyl-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
167	N-[2-(4-Ethoxy-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxyl-phenyl}-oxalamide
168	N-[2-(4-Ethoxy-3-methoxy-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
169	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-[2-(4-phenoxy-phenyl)-ethyl]-oxalamide
170	N-[2-(3-Ethoxy-4-methoxy-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
171	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-pyridin-2-yl-ethyl)-oxalamide
172	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-[2-pyridin-4-yl-ethyl)-oxalamide
173	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy)-phenyl}-N'-[2-(4-fluoro-phenyl)-ethyl]-oxalamide
174	N-[2-(2-Bromo-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
175	N-[2-(2-Chloro-6-fluoro-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
176	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2R-phenyl-propyl)-oxalamide
177	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-indan-1-yl-oxalamide
178	N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-isobutyl-oxalamide
179	N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(3-methyl-butyl)-oxalamide
180	N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2R-phenyl-propyl)-oxalamide
181	N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-phenyl-propyl)-oxalamide
182	N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-indan-2-yl-oxalamide
183	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(1R-phenyl-ethyl)-oxalamide
184	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(1S-phenyl-ethyl)-oxalamide
185	N-[2-(3-Bromo-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
186	N-[2-(2,6-Dichloro-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
187	N-[2-(2,4-Dichloro-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
188	N-(2-Benzo[1,3]dioxol-5-yl-ethyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
189	N-[2-(3-Bromo-4-methoxy-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
190	N-[2-(3,5-Dimethoxy-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
191	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-o-tolyl-ethyl)-oxalamide
192	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-m-tolyl-ethyl)-oxalamide
193	N-[2-(3-Ethoxy-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
194	N-[2-(3,4-Dimethyl-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
195	N-[2-(2,5-Dimethyl-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
196	N-[2-(3-Chloro-4-propoxy-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
197	N-[2-(4-Butoxy-3-chloro-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
198	N-[2-(4-tert-Butyl-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxyl-phenyl}-oxalamide
199	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-[2-(4-sulfamoyl-phenyl)-ethyl]-oxalamide
200	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-[2-(4-hydroxy-3-methoxy-phenyl)-ethyl]-oxalamide
201	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-[2-(3-hydroxy-4-methoxy-phenyl)-ethyl]-oxalamide
202	N-(2,4-Dichloro-benzyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxyl-phenyl}-oxalamide
203	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(4-fluoro-2-trifluoromethyl-benzyl)-oxalamide
204	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(1-p-tolyl-ethyl)-oxalamide
205	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(3-fluoro-4-trifluoromethyl-benzyl)-oxalamide
206	N-(3-Chloro-4-fluoro-benzyl)-N'-(3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
207	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-[1-(3-methoxy-phenyl)-ethyl]-oxalamide
208	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(1-naphthalen-2-yl-ethyl)-oxalamide
209	N-(4-Chloro-3-trifluoromethyl-benzyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
210	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(1-p-tolyl-ethyl)-oxalamide
211	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(6-trifluoromethyl-pyridin-3-ylmethyl)-oxalamide
212	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-methyl-benzyl)-oxalamide
213	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(3-methyl-benzyl)-oxalamide
214	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(4-fluoro-3-trifluoromethyl-benzyl)-oxalamide
215	N-(3,5-Dichloro-benzyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
216	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(1R,2,3,4-tetrahydro-naphthalen-1-yl)-oxalamide
217	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(1S,2,3,4-tetrahydro-naphthalen-1-yl)-oxalamide
218	N-Cyclopentyl-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy-phenyl}-oxalamide
219	N-[1-(4-Bromo-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
220	N-(2-Fluoro-benzyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin4-yloxy]-phenyl}-oxalamide
221	N-[2-(3,4-Dichloro-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
222	N-(4-Fluoro-benzyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxyl-phenyl}-oxalamide
223	N-(2,3-Difluoro-benxyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
224	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-phenoxy-ethy)-oxalamide
225	N-(2,2-Diphenyl-ethyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
226	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-[2-(4-methoxy-phenyl)-ethyl]-oxalamide
227	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}}-N'-(2-phenyl-propyl)-oxalamide
228	N-[2-(4-Bromo-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
229	N-{4-[7-(1-Ethyl-piperidin-4-ylmethoxy)-6-methoxy-quinolin-4-yloxy]-3-fluoro-phenyl}-2-oxo-2-(2-phenyl-morpholin-4-yl)-acetamide
230	N-{3-Fluorl-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(3-fluoro-5-trifluoromethyl-benzyl)-oxalamide
231	N-(3,5-Difluoro-benzyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
232	N-(2-Chloro-5-trifluoromethyl-benzyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
233	N-[4-(6,7-Dimethoxy-quinolin-4-yloxy)-3-fluoro-phenyl]-N'-(2-dimethylamino-2-phenyl-ethyl)-oxalamide
234	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(4-methoxy-benzyl)-oxalamide
235	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(4-trifluoromethyl-benzyl)-oxalamide
236	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(3-methoxy-benzyl)-oxalamide
237	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(3-trifluoromethyl-benzyl)-oxalamide
238	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(3-trifluoromethoxy-benzyl)-oxalamide
239	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-methoxy-benzyl)-oxalamide
240	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-trifluoromethyl-benzyl)-oxalamide
241	N-(3-Chloro-benzyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
242	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-trifluoromethoxy-benzyl)-oxalamide
243	N-(2-Chloro-benzyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
244	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(4-trifluoromethoxy-benzyl)-oxalamide
245	N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(4-methoxy-benzyl)-oxalamide
246	N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(4-trifluoromethyl-benzyl)-oxalamide
247	N-{4-[7-(Azetidin-3-ylmethoxy)-6-methoxy-quinolin-4-yloxy]-3-fluorophenyl}-N'-phenethyl-oxalamide
248	N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-azetidin-3-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-phenethyl-oxalamide
249	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-hydroxy-2-phenyl-ethyl)-oxalamide
250	N-[5-Chloro-6-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-3-yl]-N'-(2,4-difluoro-phenyl)-malonamide
251	N-[5-Chloro-6-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-3-yl]-N'-(4-fluoro-phenyl)-N'-methyl-malonamide
252	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(1R-phenyl-propyl)-oxalamide
253	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(1R-phenyl-propyl)-oxalamide
254	N-(3,4-Difluoro-benzyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
255	N-(2,6-Difluoro-benzyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
256	N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-[2-(4-fluoro-phenyl)-ethyl]-oxalamide
257	N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinolin-4-yloxyl-phenyl}-N'-phenyl-oxalamide
258	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(3-fluoro-phenyl)-oxalamide
259	N-(4-Chloro-3-fluoro-phenyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
260	N-(3,4-Dimethoxy-phenyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
261	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(3-methyl-butyl)-oxalamide
262	N-(3,3-Dimethyl-butyl)-N'-(3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
263	N-{5-Chloro-6-[6-methoxy-7-(3-piperidin-1-yl-propoxy)-quinolin-4-yloxyl-pyridin-3-yl}-N'-(4-fluoro-phenyl)-malonamide
264	N-{5-Chloro-6-[6-methoxy-7-(3-morpholin-4-yl-propoxy)-quinolin-4-yloxy]-pyridin-3-yl}-N-(4-fluoro-phenyl)-malonamide
265	N-{5-Chloro-6-[7-(3-diethylamino-propoxy)-6-methoxy-quinolin-4-yloxy]-pyridin-3-yl}-N'-(4-fluoro-phenyl)-malonamide
266	N-(4-Chloro-benzyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
267	N-(3,5-Dimethoxy-benzyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
268	N-(4-Butyl-benzyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxyl-phenyl}-oxalamide
269	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-p-tolyl-ethyl)-oxalamide
270	N-(3,5-Bis-trifluoromethyl-benzyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
271	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-pyrazin-2-ylmethyl-oxalamide
272	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-pyridin-2-ylmethyl-oxalamide
273	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinazolin-4-yloxy]-phenyl}-N'-phenethyl-oxalamide
274	N-{3-Fluoro-4-[6-methoxy-7-(1-methyl-piperidin-4-ylmethoxy)-quinazolin-4-yloxy]-phenyl}-N'-phenethyl-oxalamide
275	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-fluoro-3-trifluoromethyl-benzyl)-oxalamide
276	N-[2-(2-Bromo-6-methoxy-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
277	N-[2-(3,4-Dimethoxy-phenyl)-ethyl]-N-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N-methyl-oxalamide
278	N-[2-(5-Bromo-2-methoxy-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
279	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-fluoro-5-trifluoromethyl-benzyl)-oxalamide
280	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-[1-(4-fluoro-phenyl)-ethyl]-oxalamide
281	N-(1S-Benzyl-2-oxo-2-pyrrolidin-1-yl-ethyl)-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
282	N-{3-Fluoro-4-[6-methoxy-7-(octahydro-cyclopenta[c]pyrrol-5-ylmethoxy)-quinazolin-4-yloxy]-phenyl}-N'-phenethyl-oxalamide
283	N-[2-(4-Amino-phenyl)-ethyl]-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
284	2-(4-Benzyl-piperidin-1-yl)-N-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-2-oxo-acetamide
285	N-[4-(6,7-Dimethoxy-quinolin-4-yloxy)-phenyl]-N'-(4-fluoro-phenyl)-malonamide
286	N-[5-Chloro-6-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-3-yl]-N'-(3-fluoro-phenyl)-malonamide
287	N-[5-Chloro-6-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-3-yl]-N'-phenyl-malonamide
288	N-[5-Chloro-6-(6,7-dimethoxy-quinolin-4-yloxy)-pyridin-3-yl]-N'-(4-fluoro-phenyl)-2,2-dimethyl-malonamide
289	N-Ethyl-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
290	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-isopropyl-oxalamide
291	N-Butyl-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
292	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-methoxy-ethyl)-oxalamide
293	N-Cyclopropylmethyl-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-oxalamide
294	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N'-(2-morpholin-4-yl-ethyl)-oxalamide
295	N-{3-Fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-2-oxo-2-pyrrolidin-1-yl-acetamide
296	N-Ethyl-N'-{3-fluoro-4-[6-methoxy-7-(piperidin-4-ylmethoxy)-quinolin-4-yloxy]-phenyl}-N-methyl-oxalamide

Table 3c.

Additional Representative c-MET, c-KIT, and/or Flt-3 Inhibitors

[0232] The Compounds in Table 3c can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 3c can be used.

Entry	Name
1	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
2	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N'-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide
3	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N'-(phenylmethyl)cyclopropane-1,1-dicarboxamide
4	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N'-phenylcyclopropane-1,1-dicarboxamide
5	N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
6	N-[3-fluoro-4-({6-(methyloxy)-7-[(3-piperidin-1-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
7	N-[3-fluoro-4-({6-(methyloxy)-7-[(3-piperidin-1-ylpropyl)oxy]quinolin-4-yl}oxy)pheny]-N'-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide
8	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloropyridin-3-yl)-N'-(2-phenylethyl)cyclopropane-1,1-dicarboxamide
9	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-2-methylpyridin-3-yl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
10	N-{4-[(7-chloroquinolin-4-yl)oxy]-3-fluorophenyl}-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
11	N-{4-[(7-chloroquinolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
12	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
13	N-(4-{[6,7-bis(methyloxy)quinazolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
14	N-(4-{[6,7-bis(methyloxy)quinazolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
15	N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
16	N-{5-chloro-6-[(6-(methyloxy)-7-{[(1-methylpiperidin-4-yl)methyl]oxy}quinolin-4-yl)oxy]pyridin-3-yl}-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
17	N-[5-chloro-6-([6-(methyloxy)-7-[(piperidin-4-ylmethyl)oxy]quinolin-4-yl}oxy)pyridin-3-yl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
18	N-[5-chloro-6-({6-(methyloxy)-7-[(phenylmethyl)oxy]quinolin-4-yl}oxy)pyridin-3-yl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
19	N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)cycloropane-1,1-dicarboxamide
20	N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide
21	N-{3-fluoro-4-[(6-(methyloxy)-7-{[(1-methylpiperidin-4-yl)methyl]oxy}quinazolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
22	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-2-methylphenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
23	N-(4-fluorophenyl)-N'-[2-methyl-6-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)pyridin-3-yl]cyclopropane-1,1-dicarboxamide
24	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy-3-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
25	N-(6-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-chloro-2-methylpyridin-3-yl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
26	N-[3-fluoro-4-({7-(methyloxy)-6-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
27	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy-3,5-difluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
28	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-2,5-difluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
29	N-[3-fluoro-4-({7-(methyloxy)-6-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
30	N-{3-fluoro-4-[(6-(methyloxy)-7-(2-methyloctahydrocyclo-penta[c]pyrrol-5-ylmethoxy)quinazolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
31	N-{3-fluoro-4-[(7-(methyloxy)-6-{[(1-methylpiperidin-4-yl)methyl]oxy}quinazolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
32	N-[5-fluoro-2-methyl-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
33	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-2,3,5-trifluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
34	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-5-fluoro-2-methylphenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
35	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}-2-chloro-5-methylphenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
36	N-(3-fluorl-4-{[6-hydroxy-7-(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
37	N-(4-fluorophenyl)-N'-[2-methyl-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]cyclopropane-1,1-dicarboxamide
38	N-[3-fluoro-4-(6-(methyloxy)-7-[(3-piperazin-1-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
39	N-{3-fluoro-4-[(6-(methyloxy)-7-{[3-(4-methylpiperazin-1-yl)propyl]oxy}quinolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
40	N-{3-fluoro-4-[(6-(methyloxy)-7-{[(1-methylpiperidin-4-yl)methyl]oxy}quinolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
41	N-(4-fluorophenyl)-N'-[4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl)oxy)phenyl]cyclopropane-1,1-dicarboxamide
42	N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
43	N-(4-{[6,7-bis(methyloxy)quinolin4-yl]oxy}-2-chloro-5-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
44	N-(4-{[6,7-bis(methyloxy)-2-(methylthio)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
45	N-(4-fluorophenyl)-N'-(4-{[2-methyl-6,7-bis(methyloxy)quinazolin-4-yl]oxy}phenyl)cyclopropane-1,1-dicarboxamide
46	N-(4-{[2-amino-6,7-bis(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
47	N-(3-fluoro-4-{[2-(methylamino)-6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
48	(1S,2R)-N-(3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)-2-methylcyclopropane-1,1-dicarboxamide
49	(1R,2R)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)-2-methylcyclopropane-1,1-dicarboxamide
50	N-(4-{[6-{[3-(diethylamino)propyl]oxy}-7-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
51	N-(4-{[6-{[2-(diethylamino)ethyl]oxy}-7-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
52	1,1-dimethylethyl 4-(3-{[4-[(2-fluoro-4-{[(1-{[(4-fluorophenyl)amino]carbonyl}cyclopropyl)carbonyl]amino}phenyl)oxy]-6-(methyloxy)quinolin-7-yl]oxy}propyl)piperazine-1-carboxylate
53	(1R,2R)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)-2-methylcyclopropane-1,1-dicarboxamide
54	(1R,2R)-N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinazolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)-2-methylcyclopropane-1,1-dicarboxamide
55	N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinazolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
56	N-(4-{[7-{[3-(4-acetylpiperazin-1-yl)propyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
57	1,1-dimethylethyl 4-(3-{[4-[(2-fluoro-4-{[((1R,2R)-1-{[(4-fluorophenyl)amino]carbonyl}-2-methylcyclopropyl)carbonyl]amino}phenyl)oxy]-6-(methyloxy)quinolin-7-yl]oxy}propyl)piperazine-1-carboxylate
58	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)-1-(phenylmethyl)azetidine-3,3-dicarboxamide
59	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)azetidine-3,3-dicarboxamide
60	(1R,2S)-N-{3-fluoro-4-[(6-(methyloxy)-7-{[3-(4-methylpiperazin-1-yl)propyl]oxy}quinolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)-2-methylcyclopropane-1,1-dicarboxamide
61	(1R,2R)-N-{3-fluoro-4-[(6-(methyloxy)-7-{[3-(4-methylpiperazin-1-yl)propyl]oxy}quinolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)-2-methylcyclopropane-1,1-dicarboxamide
62	(1R,2R)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-piperazin-1-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)-2-methylcyclopropane-1,1-dicarboxamide
63	N-(3-fluoro-4-{[7-({3-[4-(1-methylethyl)piperazin-1-yl]propyl}oxy)-6-(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
64	N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinazolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
65	(1R,2R)-N-(4-{[7-{[3-(diethylamino)propyl)oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)-2-methylcyclopropane-1,1-dicarboxamide
66	(1R,2R)-N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)-2-methylcyclopropane-1,1-dicarboxamide
67	(1R,2S)-N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)-2-methylcyclopropane-1,1-dicarboxamide
68	(1R,2S)-N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)-2-methylcyclopropane-1,1-dicarboxamide
69	N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinazolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide
70	(1R,2S)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-piperazin-1-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)-2-methylcyclopropane-1,1-dicarboxamide
71	(1R,2R,3S)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-dicarboxamide
72	(1R,2R,3S)-N-{3-fluoro-4-[(6-(methyloxy)-7-{[3-(4-methylpiperazin-1-yl)propyl]oxy}quinolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-dicarboxamide
73	(1R,2R,3S)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-dicarboxamide
74	(1R,2R,3S)-N-{3-fluoro-4-[(6-(methyloxy)-7-{[3-(4-methylpiperazin-1-yl)propyl]oxy}quinazolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-dicarboxamide
75	N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide
76	(2R,3R)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-dicarboxamide
77	(2R,3R)-N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-dicarboxamide
78	N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)-2,2-dimethylcyclopropane-1,1-dicarboxamide
79	N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)-2,2-dimethylcyclopropane-1,1-dicarboxamide
80	(1R,2R,3S)-N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-dicarboxamide
81	N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)-2,2-dimethylcyclopropane-1,1-dicarboxamide
82	(1R,2R,3S)-N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-dicarboxamide
83	N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy)quinolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)-2,2-dimethylcyclopropane-1,1-dicarboxamide
84	N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinazolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)-2,2-dimethylcyclopropane-1,1-dicarboxamide
85	N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinazolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)-2,2-dimethylcyclopropane-1,1-dicarboxamide
86	N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinazolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide
87	N-{3-fluoro-4-[(6-(methyloxy)-7-{[3-(4-methylpiperazin-1-yl)propyl]oxy}quinazolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide
88 .	N-[3-fluoro-4-({6-(methyloxy)-7-[(3-piperazin-1-ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)cvclobutane-1,1-dicarboxamide
89	(2R,3R)-N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-dicarboxamide
90	N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide
91	N-{3-fluoro-4-[(6-(methyloxy)-7-{[3-(4-methylpiperazin-1-yl)propyl]oxy}quinolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)cyclobutane-1,1-dicarboxamide
92	(1R,2R)-N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinazolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)-2-methylcyclopropane-1,1-dicarboxamide
93	(1R,2R)-N-{3-fluoro-4-[(6-(methyloxy)-7-{[3-(4-methylpiperazin-1-yl)propyl]oxy}quinazolin-4-yl)oxy]phenyl}-N'-(4-fluorophenyl)-2-methylcyclopropane-1,1-dicarboxamide
94	(2R,3R)-N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinazolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-dicarboxamide
95	(2R,3R)-N-(4-{[7-{[3-(diethylamino)propyl]oxy}-6-(methyloxy)quinazolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-dicarboxamide
96	(1R,2R)-N-(3-fluoro-4-({6-(methyloxy)-7-[(3-piperazin-1-ylpropyl)oxy]quinazolin-4-yl}oxy)phenyl]-N'-(4-fluorophenyl)-2-methylcyclopropane-1,1-dicarboxamide
97	(2R,3R)-N-(4-{[7-{[2-(diethylamino)ethyl]oxy}-6-(methyloxy)quinolin-4-yl]oxy}-3-fluorophenyl)-N'-(4-fluorophenyl)-2,3-dimethylcyclopropane-1,1-dicarboxamide
98	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-[(4-fluorophenyl)methyl]cyclopropane-1,1-dicarboxamide
99	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(2-morpholin-4-ylethyl)cyclopropane-1,1-dicarboxamide
100	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-[2-(piperidin-1-ylmethyl)phenyl]cyclopropane-1,1-dicarboxamide
101	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-[2-(pyrrolidin-1-ylmethyl)phenyl]cyclopropane-1,1-dicarboxamide
102	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-[3-(morpholin-4-ylmethyl)phenyl]cyclopropane-1,1-dicarboxamide
103	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-[2-(morpholin-4-ylmethyl)phenyl]cyclopropane-1,1-dicarboxamide
104	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-phenylcyclopropane-1,1-dicarboxamide
105	N-[3-(aminomethyl)phenyl]-N'-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)cyclopropane-1,1-dicarboxamide
106	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-[3-(piperidin-1-ylmethyl)phenyl]cyclopropane-1,1-dicarboxamide
107	N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-[3-(pyrrolidin-1-ylmethyl)phenyl]cyclopropane-1,1-dicarboxamide

Table 4.

Representative EGFR, ErbB2, and/or VEGFR Inhibitors

[0233] The Compounds in Table 4 can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 4 can be used. In particular, one or two pharmaceutically acceptable salts of a Compound of Table 4 can be used. These salt(s) are formed with one or two acids independently selected from hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, acetic acid, trifluoroacetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, 3-(4-hydroxybenzoyl)benzoic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, glucoheptonic acid, 4,4'-methylenebis-(3-hydroxy-2-ene-1-carboxylic acid), 3-phenylpropionic acid, trimethylacetic acid, tertiary butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, p-toluenesulfonic acid, and salicylic acid.

Entry	Name
1	N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-(1-methylethyl)octahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
2	N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-(1-methylethyl)octahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
3	7-({[(3aR,5r,6aS)-2-acetyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-N-(4-bromo-3-chloro-2-fluorophenyl)-6-(methyloxy)quinazolin-4-amine
4	N-(4-bromo-3-chloro-2-fluorophenyl)-6-(methyloxy)-7-{[(3aR,5r,6aS-octahydrocyclopenta[c]pyrrol-5-ylmethyl]oxy}quinazolin-4-amine
5	ethyl (3aR,6aS)-5-({[4-[(4-bromo-3-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)hexahydrocyclopenta[c]pyrrole-2(1H)-carboxylate
6	N-(4-bromo-3-chloro-2-fluorophenyl)-6-(methyloxy)-7-({[(3aR,5r,6aS)-2-(methylsulfonyl)octahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)quinazolin-4-amine
7	N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-ethyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
8	N-(3,4-dichloro-2-fluorophenyl)-6-(methyloxy)-7-({[(3aR,5r,6aS)-2-(2-methylpropyl)octahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)quinazolin-4-amine
9	N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
10	N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
11	N-(3-chloro-2,4-difluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
12	N-(4,5-dichloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
13	N-(4-bromo-5-chloro-2-fluorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
14	N-(4-bromo-2,3-dichlorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
15	N-(3,4-dichlorophenyl)-7-({[(3aR,5s,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
16	N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-ethyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
17	N-(4-bromo-3-chloro-2-fluorophenyl)-6-(methyloxy)-7-({[(3aR,5r,6aS)-2-(2-methylpropyl)octahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)quinazolin-4-amine
18	N-(4-bromo-2,3-dichlorophenyl)-7-{[(3R,9aS)-hexahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
19	N-(4,5-dichloro-2-fluorophenyl)-7-{[(3R,9aS)-hexahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
20	N-(4-bromo-5-chloro-2-fluorophenyl)-7-{[(3R,9aS)-hexahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
21	N-(3-chloro-2,4-difluorophenyl)-7-{[(3R,9aS)-hexahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
22	N-(3,4-dichloro-2-fluorophenyl)-7-{[(3S,9aS)-hexahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
23	N-(4-bromo-3-chloro-2-fluorophenyl)-7-{[(3S,9aS)-hexahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
24	N-(3-chloro-2,4-difluorophenyl)-7-{[(3S,9aS)-hexahydro-1H-[1,4]oxaxino[3,4-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
25	N-(3,4-dichlorophenyl)-7-[(hexahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl)oxy]-6-(methyloxy)quinazolin-4-amine
26	N-(4,5-dichloro-2-fluorophenyl)-7-{[(3S,9aS)-hexahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
27	N-(4-bromo-2,3-dichlorophenyl)-7-{[(3S,9aS)-hexahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
28	N-(4-bromo-5-chloro-2-fluorophenyl)-7-{[(3S,9aS)-hexahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
29	N-(3,4-dichloro-2-fluorophenyl)-7-{[(3R,9aS)-hexahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
30	N-(4-bromo-3-chloro-2-fluorophenyl)-7-{[(3R,9aS)-hexahydro-1H-[1,4]oxazino[3,4-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
31	N-(3,4-dichlorophenyl)-7-{[(3R,8aR)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
32	N-(4-bromo-5-chloro-2-fluorophenyl)-7-{[(3S,8aS)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
33	N-(3,4-dichlorophenyl)-7-{[(3S,8aR)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
34	N-(3,4-dichlorophenyl)-7-{[(3S,8aS)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
35	N-(3,4-dichlorophenyl)-7-{[(3R,8aS)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
36	N-(3,4-dichloro-2-fluorophenyl)-7-{[(3S,8aS)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
37	N-(4-bromo-3-chloro-2-fluorophenyl)-7-{[(3S,8aS)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
38	N-(3-chloro-2,4-difluorophenyl)-7-{[(3S,8aS)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
39	N-(4-bromo-2,3-dichlorophenyl)-7-{[(3S,8aS)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
40	N-(4,5-dichloro-2-fluorophenyl)-7-{[(3S,8aS)-hexahydro-1H-pyrrolo[2,1-c][1,4]oxazin-3-ylmethyl]oxy}-6-(methyloxy)quinazolin-4-amine
41	1,4:3,6-dianhydro-5-({[4-[(4-bromo-5-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-5-deoxy-2-O-methyl-D-xylo-hexitol
42	1,4:3,6-dianhydro-5-deoxy-5-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-2-O-methyl-D-glucitol
43	1,4:3,6-dianhydro-5-deoxy-5-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-2-O-methyl-D-xylo-hexitol
44	1,4:3,6-dianhydro-5-({[4-[(4-bromo-3-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-5-deoxy-2-O-methyl-D-xylo-hexitol
45	1,4:3,6-dianhydro-5-({[4-[(3-chloro-2,4-difluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-5-deoxy-2-O-methyl-D-xylo-hexitol
46	1,4:3,6-dianhydro-5-({[4-[(4-bromo-2,3-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-5-deoxy-2-O-methyl-D-glucitol
47	1,4:3,6-dianhydro-2-deoxy-2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-5-O-methyl-D-threo-hexitol
48	1,4:3,6-dianhydro-5-deoxy-5-({[4-[(4,5-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-2-O-methyl-D-glucitol
49	(3S,9aS)-3-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)hexahydro-2H-pyrido[1,2-a]pyrazin-1(6H)-one
50	(3S,9aR)-3-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)hexahydro-2H-pyrido[1,2-a]pyrazin-1(6H)-one
51	(3S,8aS)-3-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)hexahydropyrrolo[1,2-a]pyrazin-1(2H)-one
52	(3S,8aR)-3-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)hexahydropyrrolo[1,2-a]pyrazin-1(2H)-one
53	(3S,8aS)-3-({[4-[(4-bromo-3-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)hexahydropyrrolo[1,2-a]pyrazin-1(2H)-one
54	(3S,8aS)-3-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-2-methylhexahydropyrrolo[1,2-a]pyrazin-1(2H)-one
55	N-(3,4-dichlorophenyl)-7-({2-[(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)amino]ethyl}oxy)-6-(methyloxy)quinazolin-4-amine
56	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{(8aR)-tetrahydro-1H-[1,3]thiazolo[4,3-c][1,4]oxazin-6-ylmethyl]oxy}quinazolin-4-amine
57	N-(3,4-dichlorophenyl)-7-{[2-(8-methyl-8-azabicyclo[3,2,1]oct-3-yl)ethyl]oxy}-6-(methyloxy)quinazolin-4-amine
58	N-(3,4-dichlorophenyl)-7-{[(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
59	N-(3,4-dichlorophenyl)-7-{[(3aR,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]oxy}-6-(methyloxy)quinazolin-4-amine
60	N-(3,4-dichlorophenyl)-7-[(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)oxy]-6-(methyloxy)quinazolin-4-amine
61	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-5-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol
62	1,4:3,6-dianhydro-2-O-[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol
63	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol
64	1,4:3,6-dianhydro-2-O-methyl-5-O-{6-(methyloxy)-4-[(2,3,4-trichlorophenyl)amino]quinazolin-7-yl}-L-iditol
65	1,4:3,6-dianhydro-5-O-[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-O-methyl-D-xylo-hexitol
66	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-2,3-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol
67	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)-quinazolin-7-yl]-L-sorbose ethylene glycol acetal
68	1,4:3,6-dianhydro-2-O-[4-[(3-chloro-2,4-difluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol
69	1,4:3,6-dianhydro-2-O-[4-[(4,5-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol
70	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-(difluoromethyl)-L-iditol
71	1,4:3,6-dianhydro-2-O-[4-[(3-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol
72	1,4:3,6-dianhydro-2-O-[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol
73	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol
74	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-ethyl-L-iditol
75	1,4:3,6-dianhydro-2-O-[4-[(3-bromo-2-methylphenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol
76	1,4:3,6-dianhydro-2-O-[4-[(3-chloro-2-methylphenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-methyl-L-iditol
77	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-deoxy-D-xylo-hexitol
78	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-methyl-D-glucitol
79	methyl 3,6-anhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-O-methyl-alpha-L-idofuranoside
80	3,6-anhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-1,2-O-(1-methylethylidene)-beta-L-xylo-hexofuranose
81	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-deoxy-5-methylidene-D-xylo-hexitol
82	methyl 3,6-anhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-O-methyl-beta-L-idofuranoside
83	N-(3,4-dichloro-2-fluorophenyl)-6-(methyloxy)-7-[(octahydro-2H-quinolizin-3-ylmethyl)oxy]quinazolin-4-amine
84	1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-{6-(methyloxy)-4-[(2,3,4-trifluorophenyl)amino]quinazolin-7-yl}-D-iditol
85	1,4:3,6-dianhydro-5-O-[4-[(2-chloro-4-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
86	1,4:3,6-dianhydro-5-O-[4-[(2-bromo-4-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
87	1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(2,6-difluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol
88	1,4:3,6-dianhydro-5-O-[4-[(3-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
89	1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-[4-{[4-fluoro-3-(trifluoromethyl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-D-iditol
90	1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(2,4-difluorophenyl)amino)-6-(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol
91	1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(2,5-difluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol
92	1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(2,3-difluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol
93	1,4:3,6-dianhydro-5-O-[4-[(5-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
94	1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(3,5-difluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol
95	1,4:3,6-dianhydro-5-O-[4-[(3-chloro-4-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
96	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-2-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
97	1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol
98	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-5-chtoro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
99	1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-{6-(methyloxy)-4-[(2,4,5-trifluorophenyl)amino]quinazolin-7-yl}-D-iditol
100	1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-{6-(methyloxy)-4-[(2,4,6-trifluorophenyl)amino]quinazolin-7-yl}-D-iditol
101	1,4:3,6-dianhydro-5-O-[4-({4-[(4-chlorophenyl)oxy]-3,5-difluorophenyl}amino)-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
102	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
103	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-2,3-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
104	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chloro-5-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
105	1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(4,5-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol
106	1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-{6-(methyloxy)-4-[(2,3,4-trichlorophenyl)amino]quinazolin-7-yl}-D-iditol
107	1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-{6-(methyloxy)-4-[(3,4,5-trichlorophenyl)amino]quinazolin-7-yl}-D-iditol
108	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
109	1,4:3,6-dianhydro-5-O-[4-[(4-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
110	1,4:3,6-dianhydro-5-O-[4-[(3-chloro-2-methylphenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
111	1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(3,4-difluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol
112	1,4:3,6-dianhydro-5-O-[4-[(2-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
113	1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-[4-[(2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-D-iditol
114	1,4:3,6-dianhydro-5-O-[4-[(3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
115	1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-[4-[(4-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-D-iditol
116	1,4:3,6-dianhydro-5-O-[4-[(4-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
117	1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(2,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol
118	1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(2,5-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol
119	1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol
120	1,4:3,6-dianhydro-5-O-[4-[(2-bromo-4,6-difluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
121	1,4:3,6-dianhydro-5-O-[4-{[4-chloro-3-(trifluoromethyl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
122	1,4:3,6-dianhydro-5-O-[4-{[2-chloro-5-(trifluoromethyl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
123	1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-[4-{[2-fluoro-3-(trifluoromethyl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-D-iditol
124	1,4:3,6-dianhydro-5-O-[4-{[2-bromo-5-(trifluoromethyl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
125	1,4:3,6-dianhydro-5-O-[4-{[2-bromo-4-(trifluoromethyl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
126	1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-[4-{[4-fluoro-2-(trifluoromethyl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-D-iditol
127	1,4:3,6-dianhydro-5-O-[4-{[3-bromo-5-(trifluoromethyl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
128	1,4:3,6-dianhydro-5-O-[4-[(2-bromophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
129	1,4:3,6-dianhydro-5-O-[4-[(3-bromophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
130	1,4:3,6-dianhydro-5-O-[4-[(4-bromophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
131	1,4:3,6-dianhydro-5-O-[4-[(3-bromo-4-methylphenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
132	1,4:3,6-dianhydro-5-O-[4-[(5-chloro-2-methylphenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
133	1,4:3,6-dianhydro-2-deoxy-5-O-[4-[(3,5-dimethylphenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol
134	1,4:3,6-dianhydro-5-O-[4-{[2,5-bis(methyloxy)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
135	1,4:3,6-dianhydro-5-O-[4-{[5-chloro-2,4-bis(methyloxy)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
136	1,4:3,6-dianhydro-5-O-[4-{[4-chloro-2,5-bis(methyloxy)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
137	1,4:3,6-dianhydro-5-O-[4-[(3-chloro-2,4-difluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-fluoro-D-iditol
138	N-(3,4-dichlorophenyl)-7-[({5-[(dimethylamino)methyl]-1,2,4-oxadiazol-3-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine
139	N-(3,4-dichlorophenyl)-7-[({3-[(dimethylamino)methyl]-1,2,4-oxadiazol-5-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine
140	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({3-[(4-methylpiperazin-1-yl)methyl]-1,2,4-oxadiazol-5-yl}methyl)oxy]quinazolin-4-amine
141	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-piperidin-4-yl-1,2,4-oxadiazol-3-yl)methyl]oxy}quinazolin-4-amine
142	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[5-(1-methylpiperidin-4-yl)-1,2,4-oxadiazol-3-yl]methyl}oxy)quinazolin-4-amine
143	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[3-(morpholin-4-ylmethyl)-1,2,4-oxadiazol-5-yl]methyl}oxy)quinazolin-4-amine
144	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(morpholin-2-ylmethyl)oxy]quinazolin-4-amine
145	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-piperidin-2-yl-1,2,4-oxadiazol-3-yl)methyl]oxy}quinazolin-4-amine
146	N-(3,4-dichlorophenyl)-7-[({2-[(dimethylamino)methyl]-1,3-thiazol-4-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine
147	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(phenylmethyl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine
148	1,1-dimethylethyl 2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholine-4-carboxylate
149	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[2-(morpholin-4-ylmethyl)-1,3-thiazol-4-yl]methyl}oxy)quinazolin-4-amine
150	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({2-[(4-methylpiperazin-1-yl)methyl]-1,3-thiazol-4-yl}methyl)oxy]quinazolin-4-amine
151	N-(3,4-dichlorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
152	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(1,4-oxazepan-2-ylmethyl)oxy]quinazolin-4-amine
153	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-piperidin-3-yl-1,2,4-oxadiazol-3-yl)methyl]oxy}quinazolin-4-amine
154	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[5-(1-methylpiperidin-2-yl)-1,2,4-oxadiazol-3-yl]methyl}oxy)quinazolin-4-amine
155	N-(3,4-dichlorophenyl)-7-{[(4-methyl-1,4-oxazepan-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
156	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[5-(1-methylpiperidin-3-yl)-1,2,4-oxadiazol-3-yl]methyl}oxy)quinazolin-4-amine
157	N-(3,4-dichlorophenyl)-7-({[5-(1,1-dimethylethyl)-1,2,4-oxadiazol-3-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
158	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(2-phenyl-1,3-thiazol-4-yl)methyl]oxy}quinazolin-4-amine
159	7-[(2,1,3-benzothiadiazol-4-ylmethyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
160	N-(3,4-dichlorophenyl)-7-{[(5-methylisoxazol-3-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
161	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-methyl-4-phenylisoxazol-3-yl)methyl]oxy}quinazolin-4-amine
162	7-[(1,3-benzothiazol-2-ylmethyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
163	7-[(2,1,3-benzoxadiazol-5-ylmethyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazol in-4-amine
164	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[2-(2-thienyl)-1,3-thiazol-4-yl]methyl}oxy)quinazolin-4-amine
165	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(1-phenyl-1H-pyrazol-4-yl)methyl]oxy}quinazolin-4-amine
166	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}methyl)oxy]quinazolin-4-amine
167	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({5-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}methyl)oxy]quinazolin-4-amine
168	7-({[3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
169	7-({[6-bromo-2-(methyloxy)naphthalen-1-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
170	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(1,3-thiazol-4-ylmethyl)oxy]quinazolin-4-amine
171	7-{[(6-chloropyridin-3-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
172	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(pyridin-4-ylmethyl)oxy]quinazolin-4-amine
173	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(2-methyl-1,3-thiazol-4-yl)methyl]oxy}quinazolin-4-amine
174	7-{[(6-chloro-4H-1,3-benzodioxin-8-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
175	7-{[(5-chloro-1-methyl-3-phenyl-1H-pyrazol-4-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
176	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[1-methyl-3-(trifluoromethyl)-1H-thieno[2,3-c]pyrazol-5-yl]methyl}oxy)quinazolin-4-amine
177	N-(3,4-dichlorophenyl-6-(methyloxy)-7-{[(3-phenylisoxazol-5-yl)methyl]oxy}quinazolin-4-amine
178	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(2,4,6-trimethylphenyl)methyl]oxy}quinazolin-4-amine
179	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(pyridin-3-ylmethyl)oxy]quinazolin-4-amine
180	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({3-[4-(methyloxy)phenyl]isoxazol-5-yl}methyl)oxy]quinazolin-4-amine
181	N-(3,4-dichlorophenyl)-7-({[5-[(2,4-dichlorophenyl)oxy]-1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
182	7-[(cyclopropylmethyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
183	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(tetrahydrofuran-2-ylmethyl)oxy]quinazolin-4-amine
184	7-(cyclopentyloxy)-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
185	7-[(2-cyclohexylethyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
186	7-[(cyclohexylmethyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
187	7-[(cyclobutylmethyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
188	N-(3,4-dichlorophenyl)-7-{[2-(1,3-dioxolan-2-yl)ethyl]oxy}-6-(methyloxy)quinazolin-4-amine
189	N-(3,4-dichlorophenyl)-7-{[2-(1,3-dioxan-2-yl)ethyl]oxy}-6-(methyloxy)quinazolin-4-amine
190	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(2-morpholin-4-ylethyl)oxy]quinazolin-4-amine
191	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(2-pyrrolidin-1-ylethyl)oxy]quinazolin-4-amine
192	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(2-piperidin-1-ylethyl)oxy]quinazolin-4-amine
193	2-(2-{[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}ethyl)-1H-isoindole-1,3(2H)-dione
194	methyl 6-O-[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-alpha-D-glucopyranoside
195	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(2-morpholin-4-yl-2-oxoethyl)oxy]quinazolin-4-amine
196	1,1-dimethylethyl 2-[3-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-1,2,4-oxadiazol-5-yl]piperidine-1-carboxylate
197	1,1-dimethylethyl 4-[3-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-1,2,4-oxadiazol-5-yl]piperidine-1-carboxylate
198	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(4-pyrrolidin-1-ylphenyl)-1,3-thiazol-2-yl]methyl}oxy)quinazolin-4-amine
199	N-(3,4-dichlorophenyl)-7-[({4-[4-(diethylamino)phenyl]-1,3-thiazol-2-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine
200	5-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-1,3-thiazol-4-yl]-2-hydroxybenzamide
201	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-pyridin-3-yl-1,3-thiazol-2-yl)methyl]oxy}quinazolin-4-amine
202	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-pyridin-2-yl-1,3-thiazol-2-yl)methyl]oxy}quinazolin-4-amine
203	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-pyridin-4-yl-1,3-thiazol-2-yl)methyl]oxy}quinazolin-4-amine
204	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(2-morpholin-4-yl-1,3-thiazol-4-yl)methyl]oxy}quinazolin-4-amine
205	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(3-morpholin-4-yl-1,2,4-oxadiazol-5-yl)methyl]oxy}quinazolin-4-amine
206	N-(3,4-dichlorophenyl)-7-({[3-(dimethylamino)-1,2,4-oxadiazol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
207	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({4-[(4-methylpiperazin-1-yl)methyl]-1,3-thiazol-2-yl}methyl)oxy]quinazolin-4-amine
208	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[(4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-ylmethyl)oxy]quinazolin-4-amine
209	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(morpholin-4-ylmethyl)-1,3-thiazol-2-yl]methyl}oxy)quinazolin-4-amine
210	N-(3,4-dichlorophenyl)-7-[({4-[(4-methyl-1,4-diazepan-1-yl)methyl]-1,3-thiazol-2-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine
211	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-{[(phenylmethyl)oxy]methyl}-1,2,4-oxadiazol-3-yl)methyl]oxy}quinazolin-4-amine
212	N-(3,4-dichlorophenyl)-7-{[(4-ethylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
213	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(2-piperidin-4-yl-1,3-thiazol-4-yl)methyl]oxy}quinazolin-4-amine
214	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[2-(1-methylpiperidin-4-yl)-1,3-thiazol-4-yl]methyl}oxy)quinazolin-4-amine
215	1,1-dimethylethyl 4-[5-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-1,2,4-oxadiazol-3-yl]piperazine-1-carboxylate
217	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(3-piperazin-1-yl-1,2,4-oxadiazol-5-yl)methyl]oxy}quinazolin-4-amine
218	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[3-(4-methylpiperazin-1-yl)-1,2,4-oxadiazol-5-yl]methyl}oxy)quinazolin-4-amine
219	N-(3,4-dichlorophenyl)-7-({[5-(1-ethylpiperidin-2-yl)-1,2,4-oxadiazol-3-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
220	N-(3,4-dichlorophenyl)-7-({[3-(4-ethylpiperazin-1-yl)-1,2,4-oxadiazol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
221	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({5-[4-(methyloxy)phenyl]-1,2,4-oxadiazol-3-yl}methyl)oxy]quinazolin-4-amine
222	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-4-yl}methyl)oxy]quinazolin-4-amine
223	7-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
224	N-(3,4-dichlorophenyl)-7-({[5-(3,5-dimethylisoxazol-4-yl)-1,2,4-oxadiazol-3-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
225	7-{[(5-chloro-1-benzothien-3-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
226	N-(3,4-dichlorophenyl)-7-[({3-[4-(1,1-dimethylethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine
227	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({5-[2-(methyloxy)phenyl]-1,2,4-oxadiazol-3-yl}methyl)oxy]quinazolin-4-amine
228	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]methyl}oxy)quinazolin-4-amine
229	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[1-(phenylmethyl)-1H-imidazol-2-yl]methyl}oxy)quinazolin-4-amine
230	N-(3,4-dichlorophenyl)-7-({[3-(2,6-dichlorophenyl)-5-methylisoxazol-4-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
231	N-(3,4-dichlorophenyl)-7-{[(6-fluoro-4H-1,3-benzodioxin-8-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
232	7-{[(3,5-dibromophenyl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
233	N-(3,4-dichiorophenyl)-7-{[(2,6-difluorophenyl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
234	N-(3,4-dichiorophenyl)-6-(methyloxy)-7-[({3-[(pyridin-2-ylsulfonyl)methyl]-1,2,4-oxadiazol-5-yl}methyl)oxy]quinazolin-4-amine
235	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-phenyl-1,2,4-oxadiazol-3-yl)methyl]oxy}quinazolin-4-amine
236	7-({[4-chloro-2-(trifluoromethyl)quinolin-6-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
237	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[2-(1-methylpyrrolidin-2-yl)ethyl]oxy}quinazolin-4-amine
238	N-(3,4-dichlorophenyl)-7-({[5-(1-ethylpiperidin-4-yl)-1,2,4-oxadiazol-3-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
239	N-(3,4-dichlorophenyl)-7-({[5-(1-ethylpiperidin-3-yl)-1,2,4-oxadiazol-3-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
240	N-(3,4-dichlorophenyl)-7-({[2-(dimethylamino)-1,3-thiazol-4-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
241	N-(3,4-dichlorophenyl)-7-{[(4-ethyl-1,4-oxazepan-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
242	N-(3,4-dichlorophenyl)-7-({[2-(1-ethylpiperidin-4-yl)-1,3-thiazol-4-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
243	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({3-[(2S)-pyrrolidin-2-yl]-1,2,4-oxadiazol-5-yl}methyl)oxy]quinazolin-4-amine
244	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({2-[(2S)-pyrrolidin-2-yl]-1,3-thiazol-4-yl}methyl)oxy]quinazolin-4-amine
245	[4-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-1,3-thiazol-2-yl]methyl benzoate
246	[4-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-1,3-thiazol-2-yl]methanol
247	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-methyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-yl)methyl]oxy}quinazolin-4-amine
248	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({2-[(4S)-1,3-thiazolidin4-yl]-1,3-thiazol-4-yl}methyl)oxy]quinazolin-4-amine
249	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(2-piperidin-2-yl-1,3-thiazol-4-yl)methyl]oxy}quinazolin-4-amine
250	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[2-(1-methylpiperidin-2-yl)-1,3-thiazol-4-yl]methyl}oxy)quinazolin-4-amine
251	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(2-piperidin-3-yl-1,3-thiazol-4-yl)methyl]oxy}quinazolin-4-amine
252	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[2-(1-methylpiperidin-3-yl)-1,3-thiazol-4-yl]methyl}oxy)quinazolin-4-amine
253	N-(3,4-dichlorophenyl)-7-({[2-(1-ethylpiperidin-2-yl)-1,3-thiazol-4-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
254	N-(3,4-dichlorophenyl)-7-({[2-(1-ethylpiperidin-3-yl)-1,3-thiazol-4-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
255	N-(3,4-dichlorophenyl)-7-[({3-[(2S)-1-ethylpyrrolidin-2-yl]-1,2,4-oxadiazol-5-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine
256	N-(3,4-dichlorophenyl)-7-[({2-[(2S)-1-ethylpyrrolidin-2-yl]-1,3-thiazol-4-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine
257	N-(3,4-dichlorophenyl)-7-{[(5-ethyl-4,5,6,7-tetrahydro[1,3]thiazolo[5,4-c]pyridin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
258	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-propyl-1,4-oxazepan-2-yl)methyl]oxy}quinazolin-4-amine
259	7-({[4-(cyclopropylmethyl)-1,4-oxazepan-2-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
260	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({4-[2-(methyloxy)ethyl]-1,4-oxazepan-2-yl}methyl)oxy]quinazolin-4-amine
261	N-(3,4-dichlorophenyl)-7-({[4-(1-methylethyl)-1,4-oxazepan-2-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
262	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(2-piperazin-1-yl-1,3-thiazol-4-yl)methyl]oxy}quinazolin-4-amine
263	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(5-pyrrolidin-2-yl-1,2,4-oxadiazol-3-yl)methyl]oxy}quinazolin-4-amine
264	N-(3,4-dichlorophenyl)-7-({[5-(1-ethylpyrrolidin-2-yl)-1,2,4-oxadiazol-3-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
265	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({3-[(2S)-1-methylpyrrolidin-2-yl]-1,2,4-oxadiazol-5-yl}methyl)oxy]quinazolin-4-amine
266	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({2-[(2S)-1-methylpyrrolidin-2-yl]-1,3-thiazol-4-yl}methyl)oxy]quinazolin-4-amine
267	N-(3,4-dichlorophenyl)-7-({[2-(4-ethylpiperazin-1-yl)-1,3-thiazol-4-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
268	N-(3,4-dichlorophenyl)-7-{[(1,4-dimethylpiperazin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
269	7-{[(4-cyclopentylmorpholin-2-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
270	N-(3,4-dichlorophenyl)-7-({[4-(1-methylethyl)morpholin-2-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
271	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(3-phenylpropyl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine
272	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({4-[2-(methyloxy)ethyl]morpholin-2-yl}methyl)oxy]quinazolin-4-amine
273	ethyl 2-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl]propanoate
274	N-(3,4-dichlorophenyl)-7-{[(4-hex-5-en-1-ylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
275	2-({2-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl]ethyl}oxy)ethanol
276	methyl 3-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl]propanoate
277	6-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl]hexanenitrile
278	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(tetrahydro-2H-pyran-2-ylmethyl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine
279	4-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl]butanenitrile
280	N-(3,4-dichlorophenyl)-7-[({4-[(4-fluorophenyl)methyl]morpholin-2-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine
281	methyl 5-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl]pentanoate
282	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-oct-7-en-1-ylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
283	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-propylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
284	6-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl]hexan-1-ol
285	7-{[(4-acetylmorpholin-2-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazol in-4-amine
286	7-({[4-(cyclopropylmethyl)morpholin-2-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
287	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-prop-2-yn-1-ylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
288	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-pyridin-4-ylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
289	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(pyridin-2-ylmethyl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine
290	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-pent-2-yn-1-ylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
291	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[2-(4-methylpiperazin-1-yl)-1,3-thiazol-4-yl]methyl}oxy)quinazolin-4-amine
292	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[5-(1-methylpyrrolidin-2-yl)-1,2,4-oxadiazol-3-yl]methyl}oxy)quinazolin-4-amine
293	N-(3-chloro-4-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
294	7-{[(4-butyl-1,4-oxazepan-2-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-(methyloxy) quinazolin-4-amine
295	(3,4-dichlorophenyl)[7-(methyloxy)-6-({[4-(2-methylpropyl)-1,4-oxazepan-2-yl]methyl}oxy)quinazolin-4-amine
296	7-{[(4-acetyl-1-ethylpiperazin-2-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
297	(3,4-dichlorophenyl)(6-(methyloxy)-7-{[(4-pentyl-1,4-oxazepan-2-yl)methyl]oxy} quinazolin-4-amine
298	(3,4-dichlorophenyl)[6-(methyloxy)-7-({[4-(tetrahydro-2H-pyran-2-ylmethyl)-1,4-oxazepan-2-yl]methyl}oxy)quinazolin-4-amine
299	(3,4-dichlorophenyl)[6-(methyloxy)-7-({[4-(3-thienylmethyl)-1,4-oxazepan-2-yl]methyl}oxy)quinazolin-4-amine
300	N-[4-chloro-2,5-bis(methyloxy)phenyl]-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
301	N-(3-bromo-2-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
302	7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)-N-(3,4,5-trichlorophenyl)quinazolin-4-amine
303	N-(3-chloro-2-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
304	N-(3,4-dichlorophenyl)-7-{[(4-ethanimidoyl-1,4-oxazepan-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
305	N-(4-bromo-2-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
306	N-(5-chloro-2-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
307	N-(4-chloro-2-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
308	N-(2,4-dichlorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
309	N-(2,4-dibromophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
310	7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)-N-(2,3,4-trichlorophenyl)quinazolin-4-amine
311	N-(3,4-dichlorophenyl)-7-{[(1-ethyl-4-methylpiperazin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
312	N'-cyano-2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholine-4-carboximidamide
313	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[2-(pyrrolidin-1-ylmethyl)-1,3-thiazol-4-yl]methyl}oxy)quinazolin-4-amine
314	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(tetrahydro-2H-pyran-4-yl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine
315	N-(3,4-dichlorophenyl)-7-({[4-(2-ethylbutyl)morpholin-2-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
316	7-({[4-(cyclohexylmethyl)morpholin-2-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
317	2-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl]ethanol
318	7-{[(4-but-2-yn-1-ylmorpholin-2-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
319	7-{[(4-cyclobutylmorpholin-2-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
320	N-(3,4-dichlorophenyl)-7-[({4-[2-(1,3-dioxolan-2-yl)ethyl]morpholin-2-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine
321	7-({[4-(2-cyclohexylethyl)morpholin-2-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
322	N-(3,4-dichlorophenyl)-7-[({4-[2-(1,3-dioxan-2-yl)ethyl]morpholin-2-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine
323	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-pent-4-en-1-ylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
324	N-(3,4-dichlorophenyl)-7-[({4-[(2R)-2-methylbutyl]morpholin-2-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine
325	N-(3,4-dichlorophenyl)-7-({[4-(4-fluorobutyl)morpholin-2-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
326	3-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl]butan-2-one
327	1-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl]butan-2-one
328	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-pentylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
329	N-(3,4-dichlorophenyl)-7-{[(4-hexylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
330	N-(3,4-dichlorophenyl)-7-{[(4-heptylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
331	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-octylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
332	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(2-phenylethyl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine
333	7-{[(4-butylmorpholin-2-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
334	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-prop-2-en-1-ylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
335	2-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl]-1-phenylethanone
336	N-(3,4-dichlorophenyl)-7-({[4-(2-fluoroethyl)morpholin-2-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
337	N-(3,4-dichlorophenyl)-7-({[4-(3-methylbut-2-en-1-yl)morpholin-2-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
338	7-[({4-[(2E)-3-bromoprop-2-en-1-yl]morpholin-2-yl}methyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
339	2-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl]acetamide
340	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({4-[3-(tetrahydro-2H-pyran-2-yloxy)propyl]-1,4-oxazepan-2-yl}methyl)oxy]quinazolin-4-amine
341	N-(3,4-dichlorophenyl)-7-({[4-(3-methylbutyl)-1,4-oxazepan-2-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
342	7-({[4-(cyclohexylmethyl)-1,4-oxazepan-2-yl]methyl}oxy)-4-[(3,4-dichlorophenyl)methyl]-6-(methyloxy)quinazoline
343	7-({[4-(2-cyclohexylethyl)-1,4-oxazepan-2-yl]methyl}oxy)-4-[(3,4-dichlorophenyl)methyl]-6-(methyloxy)quinazoline
345	N-(3,4-dichlorophenyl)-7-({[4-(2-ethylbutyl)-1,4-oxazepan-2-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
346	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(methylsulfonyl)-1,4-oxazepan-2-yl]methyl}oxy)quinazolin-4-amine
347	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(1-methylpiperidin-4-yl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine
348	N-(3-chloro-2-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
349	N'-cyano-2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-1,4-oxazepane-4-carboximidamide
350	N-(3-bromo-4-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
351	N-(3,4-dichlorophenyl)-7-{[(1,4-diethylpiperazin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
352	4-({[4-[(4-bromo-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-N'-cyanopiperidine-1-carboximidamide
353	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(methylsulfonyl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine
354	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({4-[(phenylmethyl)sulfonyl]morpholin-2-yl}methyl)oxy]quinazolin-4-amine
355	N-(3,4-dichlorophenyl)-7-[({4-[(4-fluorophenyl)sulfonyl]morpholin-2-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine
356	N-(3,4-dichlorophenyl)-7-({[4-(ethylsulfonyl)morpholin-2-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
357	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(phenylsulfonyl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine
358	7-[({4-[(3-chloropropyl)sulfonyl]morpholin-2-yl}methyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
359	7-({[4-(butylsulfonyl)morpholin-2-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
360	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({4-[(4-methylphenyl)sulfonyl]morpholin-2-yl}methyl)oxy]quinazolin-4-amine
361	N-(3,4-dichlorophenyl)-7-[({4-[(3,5-dimethylisoxazol-4-yl)carbonyl]morpholin-2-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine
362	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-{[3-(methyloxy)phenyl]acetyl}morpholin-2-yl)methyl]oxy}quinazolin-4-amine
363	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(2-methylpentanoyl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine
364	7-[({4-[(4-butylphenyl)carbonyl]morpholin-2-yl}methyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxyl)quinazolin-4-amine
365	7-[({4-[(4-chlorophenyl)acetyl]morpholin-2-yl}methyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
366	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(2-propylpentanoyl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine
367	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(4-methylpentanoyl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine
368	N-(3,4-dichlorophenyl)-7-[({4-[(2,5-difluorophenyl)carbonyl]morpholin-2-yl}methyl)oxy]-6-(methyloxy)quinazolin-4-amine
369	7-({[4-(cyclopentylcarbonyl)morpholin-2-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
370	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(2-phenylbutanoyl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine
371	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-[({4-[(2,3,6-trifluorophenyl)carbonyl]morpholin-2-yl}methyl)oxy]quinazolin-4-amine
372	N-(3,4-dichlorophenyl)-7-({[4-(furan-3-ylcarbonyl)morpholin-2-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
373	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4-propanoylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
374	N-(3,4-dichlorophenyl)-7-{[(4-hexanoylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
375	N-(3,4-dichlorophenyl)-7-({[4-(2-ethylhexanoyl)morpholin-2-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
376	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(3-phenylpropanoyl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine
377	N-(3,4-dichlorophenyl)-7-({[4-(2,2-dimethylpropanoyl)morpholin-2-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
378	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[4-(naphthalen-1-ylcarbonyl)morpholin-2-yl]methyl}oxy)quinazolin-4-amine
379	7-[({4-[(2-chloropyridin-3-yl)carbonyl]morpholin-2-yl}methyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
380	7-[({4-[(6-chloropyridin-3-yl)carbonyl]morpholin-2-yl}methyl)oxy]-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
381	7-({[4-(1,3-benzodioxol-5-ylcarbonyl)morpholin-2-yl]methyl}oxy)-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
382	N-(3,4-dichlorophenyl)-6-[(1-methylethyl)oxy]-7-[(morpholin-2-ylmethyl)oxy]quinazolin-4-amine
383	N-(3,4-dichlorophenyl)-6-{[2-(methyloxy)ethyl]oxy}-7-[(morpholin-2-ylmethyl)oxy]quinazolin-4-amine
384	N-(3,4-dichlorophenyl)-6-(ethyloxy)-7-[(morpholin-2-ylmethyl)oxy]quinazolin-4-amine
385	N-(3,4-dichlorophenyl)-6-(ethyloxy)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
386	N-(4-bromo-2-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
387	N-(4-chloro-3-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
388	N'-cyano-2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-N-methylmorpholine-4-carboximidamide
389	N-(4-bromo-3-chlorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
390	N-(3,4-dichlorophenyl)-6-[(1-methylethyl)oxy]-7-{[(4-methylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
391	N-(3,4-dichlorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-{[2-(methyloxy)ethyl]oxy}quinazolin-4-amine
392	N-(4-bromo-2-chlorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
393	7-{[(4-acetyl-1,4-oxazepan-2-yl)methyl]oxy}-N-(3,4-dichlorophenyl)-6-(methyloxy)quinazolin-4-amine
394	4-[(3,4-dichlorophenyl)amino]-7-{[(4-methylmorpholin-2-yl)methyl]oxy}quinazolin-6-ol
395	N-(3-bromo-4-chlorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
396	3-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl]-3-oxopropanoic acid
397	methyl 4-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl]-4-oxobutanoate
398	N-(3,4-dichlorophenyl)-7-{[(4-methylmorpholin-3-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
399	N-(3-bromo-2-chlorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
400	N'-cyano-2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-N-[2-(methyloxy)ethyl]morpholine-4-carboximidamide
401	N'-cyano-2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-N-ethylmorpholine-4-carboximidamide
402	[(1E)-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl](piperidin-1-yl)methylidene]cyanamide
403	[(1E)-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl](pyrrolidin-l-yl)methylidene]cyanamide
404	[(1E)-[2-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)morpholin-4-yl](4-methylpiperazin-1-yl)methylidene]cyanamide
405	N-(3,4-dichlorophenyl)-7-{[(6-ethyl-4,6-dimethylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
406	N-(4-bromo-3-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
407	N-(3,4-dichlorophenyl)-7-{[(6,6-dimethylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
408	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4,6,6-trimethylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
409	N-(3,4-dichlorophenyl)-7-{[2-(5,5-dimethylmorpholin-2-yl)ethyl]oxy}-6-(methyloxy)quinazolin-4-amine
410	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[2-(4,5,5-trimethylmorpholin-2-yl)ethyl]oxy}quinazolin-4-amine
411	1,1-dimethylethyl 2-(2-{[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}ethyl)-5,5-dimethylmorpholine-4-carboxylate
412	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[(4,5,5-trimethylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
413	N-(4-bromo-2,3-dichlorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
414	N-(4,5-dichloro-2-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
415	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-{[2-(4,6,6-trimethylmorpholin-2-yl)ethyl]oxy}quinazolin-4-amine
416	N-(4-bromo-2,3-difluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
417	N-(4-bromo-2,5-difluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
418	N-(4-bromo-3,5-difluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
419	N-(3,4-dichloro-2-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
420	N-(3,4-dichlorophenyl)-7-({[(2R,5S,6S)-5,6-dimethylmorpholin-2-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
421	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[(2R,5S,6S)-4,5,6-trimethylmorpholin-2-yl]methyl}oxy)quinazolin-4-amine
422	N-(3,4-dichlorophenyl)-6-(methyloxy)-7-({[(2S,5S,6S)-4,5,6-trimethylmorpholin-2-yl]methyl}oxy)quinazolin-4-amine
423	N-(4-bromo-3-chloro-2-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
424	N-(4-bromo-5-chloro-2-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
425	N-(4-bromo-3-chloro-2-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
426	N-(3,4-dichloro-2-fluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
427	N-(3-chloro-2,4-difluorophenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
428	N-(2,3-dichloro-4-methylphenyl)-7-{[(4-methylmorpholin-2-yl)methyl]oxy}-6-(methyloxy)quinazolin-4-amine
429	6-({[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-3,3,4-trimethylmorpholin-2-one
430	N-(4-bromo-2,3-dichlorophenyl)-6-(methyloxy)-7-{[(4,5,5-trimethylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
431	N-(4-bromo-5-chloro-2-fluorophenyl)-6-(methyloxy)-7-{[(4,5,5-trimethylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
432	N-(4,5-dichloro-2-fluorophenyl)-6-(methyloxy)-7-{[(4,5,5-trimethylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
433	N-(3,4-dichloro-2-fluorophenyl)-6-(methyloxy)-7-{[(4,5,5-trimethylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
434	N-(4-bromo-3-chloro-2-fluorophenyl)-6-(methyloxy)-7-{[(4,5,5-trimethylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
435	N-(3-chloro-2,4-difluorophenyl)-6-(methyloxy)-7-{[(4,5,5-trimethylmorpholin-2-yl)methyl]oxy}quinazolin-4-amine
436	(6S)-6-({[4-[(4-bromo-3-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-4-methylpiperazin-2-one
437	(6S)-6-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-4-methylpiperazin-2-one
438	(6S)-6-({[4-[(4-bromo-3-chloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-1,4-dimethylpiperazin-2-one
439	(6S)-6-({[4-[(3,4-dichloro-2-fluorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]oxy}methyl)-1,4-dimethylpiperazin-2-one
440	N-(4-bromo-3-chlorophenyl)-7-{[(3a'S,4R,6'S,6a'R)-2,2-dimethyltetrahydrospiro[1,3-dioxolane-4,3'-furo[3,2-b]furan]-6'-yl]oxy}-6-(methyoxy)quinazolin-4-amine
441	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-methyl-5-C-[(methyloxy)methyl]-L-glucitol
442	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-(methylsulfonyl)-L-glucitol
443	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-L-glucitol
444	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-S-methyl-5-thio-D-iditol
445	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-morpholin-4-yl-D-iditol
446	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-(4-methylpiperazin-1-yl)-D-iditol
447	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-pyrrolidin-1-yl-D-iditol
448	2-O-acetyl-1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-D-iditol
449	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-D-iditol
450	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-(methylsulfonyl)-D-iditol
451	2-amino-1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-D-iditol
452	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-(dimethylamino)-D-iditol
453	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-(diethylamino)-D-iditol
454	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-piperidin-1-yl-D-iditol
455	2-(acetylamino)-1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-D-iditol
456	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-methyl-5-C-(trifluoromethyl)-L-glucitol
457	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-[(methylsulfonyl)amino]-D-iditol
458	N-(4-bromo-3-chlorophenyl)-6-(methyloxy)-7-[(1-methylpyrrolidin-3-yl)oxy]quinazolin-4-amine
459	N-(4-bromo-3-chlorophenyl)-6-(methyloxy)-7-[(3R)-tetrahydrofuran-3-yloxy]quinazolin-4-amine
460	N-(4-bromo-3-chlorophenyl)-6-(methyloxy)-7-{[(3S,4R)-4-(methyloxy)tetrahydrofuran-3-yl]oxy}quinazolin-4-amine
461	1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-(6-(methyloxy)-4-{[4-(4-methylpiperazin-1-yl)phenyl]amino}quinazolin-7-yl)-D-iditol
462	1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-[4-{[3-fluoro-4-(4-methylpiperazin-1-yl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-D-iditol
463	1,4:3,6-dianhydro-2-deoxy-5-O-[4-{[2,3-dichloro-4-(4-methylpiperazin-1-yl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol
464	1,4:3,6-dianhydro-2-deoxy-5-O-[4-{[3,4-dichloro-2-(4-methylpiperazin-1-yl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-2-fluoro-D-iditol
465	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-C-(trifluoromethyl)-D-glucitol
466	(3,4-dichlorophenyl)[6-(methyloxy)-7-({[4-(tetrahydrofuran-2-ylmethyl)-1,4-oxazepan-2-yl]methyl}oxy)quinazolin -4-amine
467	N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
468	N-(4-bromo-3-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
469	N-(3-chloro-2,4-difluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
470	N-(4,5-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
471	N-(4-bromo-5-chloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
472	N-(4-bromo-2,3-dichlorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclo-penta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
473	N-(3,4-dichlorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
474	N-(3,4-dichlorophenyl)-7-[(2-{[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]amino}ethyl)oxy]-6-(methyloxy)quinazolin-4-amine
475	N-(3,4-dichlorophenyl)-7-({2-[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]ethyl}oxy)-6-(methyloxy)quinazolin-4-amine
476	N-(3,4-dichlorophenyl)-7-({[(3-endo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine
477	N-(3,4-dichlorophenyl)-7-{[(3-exo)-8-methyl-8-azabicyclo[3.2.1]oct-3-yl]oxy}-6-(methyloxy)quinazolin-4-amine
478	1,4:3,6-Dianhydro-5-O-[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-O-methyl-D-glucitol
479	1,4:3,6-dianhydro-5-O-{4-[(3-chloro-2-fluorophenyl)amino]-6-(methyloxy)quin-azolin-7-yl}-2-deoxy-2-fluoro-L-iditol
480	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-(methylsulfonyl)-D-glucitol
481	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-D-glucitol
482	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-S-methyl-5-thio-L-iditol
483	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-morpholin-4-yl-L-iditol
484	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-(4-methylpiperazin-1-yl)-L-iditol
485	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-pyrrolidin-1-yl-L-iditol
486	2-O-acetyl-1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-L-iditol
487	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-L-iditol
488	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-(methylsulfonyl)-L-iditol
489	2-amino-1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-L-iditol
490	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-(dimethylamino)-L-iditol
491	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-(diethylamino)-L-iditol
492	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-piperidin-1-yl-L-iditol
493	2-(acetylamino)-1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-L-iditol
494	1,4:3,6-dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-methyl-5-C-(trifluoromethyl)-D-glucitol
495	1,4:3,6-dianhydro-5-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-deoxy-2-[(methylsulfonyl)amino]-L-iditol
496	1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-(6-(methyloxy)-4-{[4-(4-methylpiperazin-1-yl)phenyl]amino}quinazolin-7-yl)-L-iditol
497	1,4:3,6-dianhydro-2-deoxy-2-fluoro-5-O-[4-{[3-fluoro-4-(4-methylpiperazin-1-yl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-L-iditol
498	1,4:3,6-dianhydro-2-deoxy-5-O-[4-{[2,3-dichloro-4-(4-methylpiperazin-1-yl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-2-fluoro-L-iditol
499	1,4:3,6-dianhydro-2-deoxy-5-O-[4-{[3,4-dichloro-2-(4-methylpiperazin-1-yl)phenyl]amino}-6-(methyloxy)quinazolin-7-yl]-2-fluoro-L-iditol
500	1,4:3,6-Dianhydro-5-O-[4-[(3,4-dichlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-2-O-methyl-D-glucitol
501	1,4:3,6-Dianhydro-2-O-[4-[(4-bromo-3-chlorophenyl)amino]-6-(methyloxy)quinazolin-7-yl]-5-O-methyl-L-glucitol

Table 5a.

Representative IGF-1R Inhibitor

[0234] The Compounds in Table 5a can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 5a can be used.

Table 5b.

Additional Representative IGF1R Inhibitors

[0235] The Compounds in Table 5b can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 5b can be used.

Entry	Structure	Name
573		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N6-[3-(diethylamino)propyl]-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}pyrimidine-2,4,6-triamine
574		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N6-[2-(diethylamino)ethyl]-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}pyrimidine-2,4,6-triamine
575		N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-N4-[5-(1-methylethyl)-1H-pyrazol-3-yl]-6-[(3S)-3-methylpiperazin-1-yl]pyrimidine-2,4-diamine
576		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-{[2-(dimethylamino)ethyl]oxy}-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}pyrimidine-2,4-diamine
577		N4-[3-(1-methylethyl)-1H-pyrazol-5-yl]-6-[(1-methylpyrrolidin-3-yl)oxy]-N2-[(3-phenylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
578		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-6-[(1-methylpyrrolidin-3-yl)oxy]pyrimidine-2,4-diamine
579		N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-N4-[3-(1-methylethyl)-1H-pyrazol-5-yl]-6-[(1-methylpyrrolidin-3-yl)oxyl]pyrimidine-2,4-diamine
580		N4-[2-(diethylamino)ethyl]-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-N6-[5-(1-methytethyl)-1H-pyrazol-3-yl]pyrimidine-2,4,6-triamine
581		N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-N4-[5-(1-methylethyl)-1H-pyrazol-3-yl]pyrimidine-2,4-diamine
582		N4-[5-(1-methylethyl)-1H-pyrazol-3-yl]-6-[(1-methylpiperidin-3-yl)oxy]-N2-[(3-phenylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
583		N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-N4-[5-(1-methylethyl)-1H-pyrazol-3-yl]-6-[(1-methylpiperidin-3-yl)oxy]pyrimidine-2,4-diamine
584		N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-methyl-2-{[(3-phenylisoxazol-5-yl)methyl]oxy}pyrimidin-4-amine
585		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-methyl-N2-[(4-phenyl-1H-imidazol-2-yl)methyl]pyrimidine-2,4-diamine
586		6-{[2-(dimethylamino)ethyl]oxy}-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-N4-[5-(1-methylethyl)-1H-pyrazol-3-yl]pyrimidine-2,4-diamine
587		N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-N4-[5-(1-methylethyl)-1H-pyrazol-3-yl]-6-[(2-morpholin-4-ylethyl)oxy]pyrimidine-2,4-diamine
588		N4-[5-(1-methylethyl)-1H-pyrazol-3-yl]-6-[(2-morpholin-4-ylethyl)oxy]-N2-[(3-phenylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
589		N4-[3-(1-methylethyl)-1H-pyrazol-5-yl]-N2-[(3-phenylisoxazol-5-yl)methyl]-6-[(2-piperidin-1-ylethyl)oxy]pyrimidine-2,4-diamine
590		N4-[3-(diethylamino)propyl]-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-N6-[5-(1-methylethyl)-1H-pyrazol-3-yl]pyrimidine-2,4,6-triamine
591		N4-[5-(1-methylethyl)-1H-pyrazol-3-yl]-6-[(3S)-3-methylpiperazin-1-yl]-N2-[(3-phenylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
592		N4-[2-(diethylamino)ethyl]-N6-[5-(1-methylethyl)-1H-pyrazol-3-yl]-N2-[(3-phenylisoxazol-5-yl)methyl]pyrimidine-2,4,6-triamine
593		N4-[5-(1-methylethyl)-1H-pyrazol-3-yl]-6-[(1-methylpiperidin-4-yl)oxy]-N2-[(3-phenylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
594		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-6-[(2-morpholin-4-ylethyl)oxy]pyrimidine-2,4-diamine
595		N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-N4-[3-(1-methylethyl)-1H-pyrazol-5-yl]-6-[(2-piperidin-1-ylethyl)oxy]pyrimidine-2,4-diamine
596		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-6-[3-(diethylamino)propyl]-N2-[(3-phenylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
597		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-6-[(2-piperidin-1-ylethyl)oxy]pyrimidine-2,4-diamine
598		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-6-[(1-methylpiperidin-3-yl)oxy]pyrimidine-2,4-diamine
599		N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-N4-[3-(1-methylethyl)-1H-pyrazol-5-yl]-6-[(1-methylpiperidin-4-yl)oxy]pyrimidine-2,4-diamine
600		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-6-methyl-N2-[(3-methylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
601		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-N2-[(3-methylisoxazol-5-yl)methyl]-6-morpholin-4-ylpyrimidine-2,4-diamine
602		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-N2-[(3-methylisoxazol-5-yl)methyl]-6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine
603		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-6-[(1-methylpiperidin-4-yl)oxy]pyrimidine-2,4-diamine
604		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-N2-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-6-morpholin-4-ylpyrimidine-2,4-diamine
605		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-N2-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine
606		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-N2-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-6-[(2-morpholin-4-ylethyl)oxy]pyrimidine-2,4-diamine
607		N2-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-N4-[3-(1-methylethyl)-1H-pyrazol-5-yl]-6-morpholin-4-ylpyrimidine-2,4-diamine
608		N2-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-N4-[3-(1-methylethyl)-1H-pyrazol-5-yl]-6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine
609		N2-{[3-(4-fluorophenyl)isoxazol-5-yl]methyl}-N4-[3-(1-methylethyl)-1H-pyrazol-5-yl]-6-[(2-morpholin-4-ylethyl)oxy]pyrimidine-2,4-diamine
610		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-methyl-N2-[(3-pyridin-3-ylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
611		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-N2-[(3-pyridin-2-ylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
612		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-morpholin-4-yl-N2-[(3-pyridin-2-ylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
613		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-6-piperazin-1-ylpyrimidine-2,4-diamine
614		6-(4-acetylpiperazin-1-yl)-N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}pyrimidine-2,4-diamine
615		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-6-[4-(methylsulfonyl)piperazin-1-yl]pyrimidine-2,4-diamine
616		4-{6-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]-2-({[3-(1-methylethyl)isoxazol-5-yl]methyl}amino)pyrimidin-4-yl}piperazine-1-carbaldehyde
617		N4-(3-methyl-1H-pyrazol-5-yl)-6-morpholin-4-yl-N2-[(3-phenylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
618		6-(4-methylpiperazin-1-yl)-N4-(3-methyl-1H-pyrazol-5-yl)-N2-[(3-phenylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
619		N4-(3-methyl-1H-pyrazol-5-yl)-6-[(2-morpholin-4-ylethyl)oxy]-N2-[(3-phenylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
620		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-methyl-N2-[(3-pyridin-4-ylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
621		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-{[3-(3,4-difluorophenyl)isoxazol-5-yl]methyl}-6-methylpyrimidine-2,4-diamine
622		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-{[3-(2,4-difluorophenyl)isoxazol-5-yl]methyl}-6-methylpyrimidine-2,4-diamine
623		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-methyl-N2-[(3-pyrazin-2-ylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
624		5-chloro-N4-(3-cyclopropyl-1H-pyrazol-5-yl)-6-morpholin-4-yl-N2-[(3-phenylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
625		5-chloro-N4-(3-cyclopropyl-1H-pyrazol-5-yl)-6-(4-methylpiperazin-1-yl)-N2-[(3-phenylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
626		N2-[(3-methylisoxazol-5-yl)methyl]-6-(4-methylpiperazin-1-yl)-N4-(3-methyl-1H-pyrazol-5-yl)pyrimidine-2,4-diamine
627		N2-[(3-methylisoxazol-5-yl)methyl]-N4-(3-methyl-1H-pyrazol-5-yl)-6-morpholin-4-ylpyrimidine-2,4-diamine
628		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-N2-[(3-pyrimidin-4-ylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
629		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-[(3-furan-3-ylisoxazol-5-yl)methyl]-6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine
630		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N6-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-N2-[(3-methylisoxazol-5-yl)methyl]pyrimidine-2,4,6-triamine
631		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl)-N2-[(3-methylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
632		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl)-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}pyrimidine-2,4-diamine
633		N4-bicyclo[2.2.1]hept-2-yl-N6-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}pyrimidine-2,4,6-triamine
634		N4-bicyclo[2.2.1]hept-2-yl-N6-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-[(3-methylisoxazol-5-yl)methyl]pyrimidine-2,4,6-triamine
635		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-[(3-methylisoxazol-5-yl)methyl]-6-[(1R,4R)-5-(phenylmethyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]pyrimidine-2,4-diamine
636		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-6-[(1R,4R)-5-(phenylmethyl)-2,5-diazabicyclo[2.2.1]hept-2-yl]pyrimidine-2,4-diamine
637		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-morpholin-4-yl-N2-[(3-pyrimidin-4-ylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
638		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-{[2-(dimethylamino)ethyl]oxy}-N2-[(3-pyrimidin-4-ylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
639		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-{[3-(5-fluoropyridin-2-yl)isoxazol-5-yl]methyl}-6-methylpyrimidine-2,4-diamine
640		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-N2-{[3-(2-thienyl)isoxazol-5-yl]methyl}pyrimidine-2,4-diamine
641		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-{[2-(dimethylamino)ethyl]oxy}-N2-[(3-pyridin-2-ylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
642		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-6-(4-methylpiperazin-1-yl)-N2-[(3-pyrimidin-5-ylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
643		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-6-morpholin-4-yl-N2-[(3-pyrimidin-5-ylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
644		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-{[2-(diethylamino)ethyl]oxy}-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}pyrimidine-2,4-diamine
645		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}-6-[(2-pyrrolidin-1-ylethyl)oxy]pyrimidine-2,4-diamine
646		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-{[2-(diethylamino)ethyl]oxy}-N2-[(3-methylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
647		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-N2-[(3-methylisoxazol-5-yl)methyl]-6-[(2-pyrrolidin-1-ylethyl)oxy]pyrimidine-2,4-diamine
648		N4-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-N2-{[3-(1,3-thiazol-2-yl)isoxazol-5-yl]methyl}pyrimidine-2,4-diamine
649		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-6-[2-(dimethylamino)ethoxy]-N2-[(3-methylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
650		6-{[2-(dimethylamino)ethyl]oxy}-N2-[(3-methylisoxazol-5-yl)methyl]-N4-(3-methyl-1H-pyrazol-5-yl)pyrimidine-2,4-diamine
651		6-{[2-(diethylamino)ethyl]oxy}-N2-[(3-methylisoxazol-5-yl)methyl]-N4-(3-methyl-1H-pyrazol-5-yl)pyrimidine-2,4-diamine
652		N2-[(3-methylisoxazol-5-yl)methyl]-N4-(3-methyl-1H-pyrazol-5-yl)-6-[(2-pyrrolidin-1-ylethyl)oxy]pyrimidine-2,4-diamine
653		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-6-methyl-N2 -[2-(3-phenylisoxazol-5-yl)ethyl]pyrimidine-2,4-diamine
654		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-6-methyl-N2-[1-(3-phenylisoxazol-5-yl)ethyl]pyrimidine-2,4-diamine
655		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-N2-[(3-ethylisoxazol-5-yl)methyl]-6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine
656		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-N2-[(3-ethylisoxazol-5-yl)methyl]-6-morpholin-4-ylpyrimidine-2,4-diamine
657		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-6-{[2-(dimethylamino)ethyl]oxy}-N2-[(3-ethylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
658		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-6-{[2-(diethylamino)ethyl]oxy}-N2-[(3-ethylisoxazol-5-yl)methyl]pyrimidine-2,4-diamine
659		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-N2-[(3-ethylisoxazol-5-yl)methyl]-6-[(2-pyrrolidin-1-ylethyl)oxy]pyrimidine-2,4-diamine
660		N2-{[3-(2-aminopyrimidin-4-yl)isoxazol-5-yl]methyl}-N4-(3-cyclopropyl-1H-pyrazol-5-yl)-6-(4-methylpiperazin-1-yl)pyrimidine-2,4-diamine
661		N4-(3-cyclopropyl-1H-pyrazol-5-yl)-6-(4-ethylpiperazin-1-yl)-N2-{[3-(1-methylethyl)isoxazol-5-yl]methyl}pyrimidine-2,4-diamine
662		2-(1-{6-[(3-cyclopropyl-1H-pyrazol-5-yl)amino]-2-({[3-(1-methylethyl)isoxazol-5-yl]methyl}amino)pyrimidin-4-yl}piperidin-4-yl)ethanol
663		2-(4-{6-[(3-cyclopropyl-1H-pyrazol-5-yl)amino]-2-({[3-(1-methylethyl)isoxazol-5-yl]methyl}amino)pyrimidin-4-yl}piperazin-1-yl)ethanol

Table 6.

Representative Raf Inhibitors

[0236] The Compounds in Table 6 can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 6 can be used.

Entry	Name
1	6-(2-butyl-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one
2	6-[1-hydroxy-3-oxo-2-(2-phenylethyl)-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
3	6-(1-hydroxy-2-{[4-(methyloxy)phenyl]methyl}-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one
4	6-(1-hydroxy-2-{[3-(methyloxy)phenyl]methyl}-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one
5	6-{2-[(4-fluorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
6	6-(1-hydroxy-3-oxo-2-phenyl-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one
7	6-{2-[(3-bromophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
8	6-{2-[(4-bromophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
9	6-[1-hydroxy-3-oxo-2-(3-phenylpropyl)-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
10	6-{2-[(3,4-dichlorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
11	6-{1-hydroxy-2-[(4-methylphenyl)methyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
12	6-{2-[(4-chlorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
13	6-[1-hydroxy-2-(1-methylethyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
14	methyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
15	6-{2-[(3,4-dimethylphenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
16	6-(2-{[4-chloro-3-(trifluoromethyl)phenyl]methyl}-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one
17	6-(2-{[4-(dimethylamino)phenyl]methyl}-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one
18	6-[2-(3-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
19	6-[2-(4-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
20	6-[2-(3,4-dichlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
21	6-[1-hydroxy-2-(4-methylphenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
22	3-(2-{[3,5-bis(methyloxy)phenyl]amino}-1H-benzimidazol-5-yl)-3-(methyloxy)-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one
23	3-(2-{[3,5-bis(methyloxy)phenyl]amino}-1H-benzimidazol-5-yl)-2-(1-methylethyl)-3-(methyloxy)-2,3-dihydro-1H-isoindol-1-one
24	3-(2-{[3,5-bis(methyloxy)phenyl]amino}-1H-benzimidazol-5-yl)-3-hydroxy-2-phenyl-2,3-dihydro-1H-isoindol-1-one
25	3-(2-{[3,5-bis(methyloxy)phenyl]amino}-1H-benzimidazol-5-yl)-3-hydroxy-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one
26	methyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1-methyl-1H-benzimidazol-2-yl}carbamate
27	3-(1H-benzimidazol-5-yl)-3-hydroxy-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one
28	5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-N-methyl-1H-benzimidazole-2-carboxamide
29	3-hydroxy-3-(2-methyl-1H-benzimidazol-5-yl)-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one
30	7-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-3,4-dihydroquinoxalin-2(1H)-one
31	7-[2-(3-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-3,4-dihydroquinoxalin-2(1H)-one
32	1,1-dimethylethyl 4-{[1-hydroxy-3-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-1,3-dihydro-2H-isoindol-2-yl]methyl}piperidine-1-carboxylate
33	6-(1-hydroxy-2-{[2-(methyloxy)phenyl]methyl}-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one
34	6-{2-[(3-chlorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
35	6-{2-[(2-chlorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
36	6-{2-[(3-fluorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isondol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
37	6-{2-[(2-bromophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
38	6-{2-[(2-fluorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
39	6-[2-(3-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
40	6-[1-hydroxy-2-(3-iodophenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
41	6-[2-(3-bromophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
42	6-[1-hydroxy-2-(3-nitrophenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
43	6-{1-hydroxy-2-[3-(methyloxy)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
44	6-[1-hydroxy-2-(3-methylphenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
45	3-hydroxy-3-(1H-indol-5-yl)-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one
46	methyl [6-(1-hydroxy-3-oxo-2-phenyl-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate
47	6-[2-(2-aminophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
48	6-{[2-(3-phenyl-1,2,4-oxadiazol-5-yl)phenyl]carbonyl}-2H-1,4-benzoxazin-3(4H)-one
49	6-{[2-(1H-benzimidazol-2-yl)phenyl]carbonyl}-2H-1,4-benzoxazin-3(4H)-one
50	6-(1-hydroxy-3-oxo-2-{[2-(trifluoromethyl)phenyl]methyl}-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one
51	6-{2-[(5-bromo-2-fluorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
52	6-{1-hydroxy-2-[(3-nitrophenyl)methyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
53	6-(1-hydroxy-3-oxo-2-{[3-(trifluoromethyl)phenyl]methyl}-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one
54	6-(2-{[2,3-bis(methyloxy)phenyl]methyl}-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one
55	6-{1-hydroxy-2-[(3-iodophenyl)methyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
56	6-[1-hydroxy-3-oxo-2-({3-[(trifluoromethyl)oxy]phenyl}methyl)-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
57	6-(1-hydroxy-2-{[2-(methylthio)phenyl]methyl}-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one
58	6-[2-(3,4-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
59	6-{1-hydroxy-2-[3-(1-methylethyl)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
60	6-(1-hydroxy-3-oxo-2-{3-[(trifluoromethyl)oxy]phenyl}-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one
61	6-{1-hydroxy-3-oxo-2-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
62	3-[1-hydroxy-3-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-1,3-dihydro-2H-isoindol-2-yllbenzenesulfonamide
63	6-{2-[5-chloro-2-(methyloxy)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
64	6-{2-[4-fluoro-3-(trifluoromethyl)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
65	3-hydroxy-3-(1H-indol-6-yl)-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one
66	6-[2-(3-fluoro-5-iodophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
67	6-[2-(3-aminophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
68	6-[2-(3,5-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
69	6-{1-hydroxy-2-[3-(methylsulfonyl)phenyl]-3-oxo-2,3-dihydro-1H isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
70	ethyl 3-[1-hydroxy-3-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-1,3-dihydro-2H-isoindol-2-yl]benzoate
71	3-[1-hydroxy-3-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-1,3-dihydro-2H-isoindol-2-yl]benzonitrile
72	6-[2-(2-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
73	6-[2-(3-amino-5-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
74	6-[2-(5-chloro-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
75	6-[2-(3-chloro-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
76	6-[2-(3-ethylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
77	6-[2-(3-ethynylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
78	6-[1-hydroxy-2-(3-hydroxyphenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
79	6-{1-hydroxy-3-oxo-2-[3-(phenyloxy)phenyl]-2,3-dihydro-1H-isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
80	6-(1-hydroxy-3-oxo-2-{3-[(phenylmethyl)oxy]phenyl}-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one
81	3-[1-hydroxy-3-oxo-1-(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)-1,3-dihydro-2H-isoindol-2-yl]benzamide
82	6-{1-hydroxy-2-[3-(hydroxymethyl)phenyl]-3-oxo-2,3-dihydro-1H isoindol-1-yl}-2H-1,4-benzoxazin-3(4H)-one
83	6-[2-(2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
84	3-hydroxy-3-[2-(methylamino)-1H-benzimidazol-5-yl]-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one
85	6-(2-biphenyl-3-yl-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one
86	6-(2-{3-[(dimethylamino)methyl]phenyl}-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one
87	6-[2-(3,5-dichlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
88	6-(1-hydroxy-3-oxo-2-piperidin-4-yl-2,3-dihydro-1H-isoindol-1-yl)-2H-1,4-benzoxazin-3(4H)-one
89	6-[2-(3-{[2-(dimethylamino)ethyl]oxy}phenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
90	6-[1-hydroxy-2-(2-methylphenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-2H-1,4-benzoxazin-3(4H)-one
91	N-methyl-2-[(3-oxo-3,4-dihydro-2H-1,4-benzoxazin-6-yl)carbonyl]-N-phenylbenzamide
92	methyl {5-[1-(ethyloxy)-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
93	phenylmethyl 2-[(2-{[(methyloxy)carbonyl]amino}-1H-benzimidazol-5-yl)carbonyl]benzoate
94	3-hydroxy-3-(1H-indazol-5-yl)-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one
95	3-hydroxy-3-(1H-indazol-6-yl)-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one
96	ethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
97	2-methylpropyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
98	methyl {5-[1-hydroxy-3-oxo-2-(2-thienylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
99	methyl {5-[1-hydroxy-3-oxo-2-(2-phenylethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
100	3-[2-amino-1-(1,1-dimethylethyl)-1H-benzimidazol-5-yl]-3-hydroxy-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one
101	3-(2-amino-1H-benzimidazol-5-yl)-3-hydroxy-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-one
102	methyl [5-(1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate
103	3-(methyloxy)butyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
104	methyl (5-{1-hydroxy-3-oxo-2-[(1R)-1-phenylethyl]-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
105	methyl (5-{1-hydroxy-3-oxo-2-[(1S)-1-phenylethyl]-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
106	2-(methyloxy)ethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
107	methyl {6-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1-methyl-1H-benzimidazol-2-yl}carbamate
108	prop-2-yn-1-yl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
109	but-2-yn-1-yl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
110	1-methylethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
111	methyl {5-[2-(2,3-dihydro-1H-inden-2-yl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
112	methyl {5-[1-hydroxy-3-oxo-2-(pyridin-4-ylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
113	methyl {5-[1-hydroxy-3-oxo-2-(pyridin-3-ylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
114	methyl (6-{2-[(3-fluorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
115	methyl {5-[1-hydroxy-2-(3-methylphenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
116	methyl [5-(1-hydroxy-2-{[2-(methyloxy)phenyl]methyl}-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate
117	methyl [5-(1-hydroxy-2-{[3-(methyloxy)phenyl]methyl}-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate
118	methyl [5-(1-hydroxy-2-{[4-(methyloxy)phenyl]methyl}-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate
119	methyl (6-{2-[(4-fluorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
120	methyl (6-{2-[(3-bromophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
121	methyl (5-{1-hydroxy-2-[(3-iodophenyl)methyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
122	methyl (5-{2-[(3-chlorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
123	methyl (5-{2-[(2-fluorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
124	methyl {5-[1-hydroxy-3-oxo-2-(pyridin-2-ylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
125	phenylmethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
126	2-fluoroethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
127	propyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
128	methyl (5-{1-hydroxy-2-[4-(methyloxy)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
129	methyl (5-{2-[(2-chlorophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
130	methyl (5-{2-[(2-bromophenyl)methyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
131	methyl (5-{1-hydroxy-2-[(3-methylphenyl)methyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
132	methyl (5-{1-hydroxy-2-[(4-methylphenyl)methyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
133	methyl (5-{1-hydroxy-2-[(2-methylphenyl)methyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
134	methyl {5-[2-(3-bromophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
135	methyl {5-[2-(3-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
136	methyl {5-[2-(3-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
137	methyl (5-{1-hydroxy-2-[3-(methyloxy)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
138	methyl {5-[2-(4-bromophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
139	methyl {5-[2-(4-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
140	methyl {5-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
141	methyl {5-[2-(3,5-dimethylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
142	methyl {5-[2-(2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
143	methyl {5-[2-(2-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
144	methyl {5-[1-hydroxy-2-(2-methylphenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
145	methyl (5-{1-hydroxy-2-[2-(methyloxy)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
146	methyl {5-[1-hydroxy-2-(4-methylphenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1 H-benzimidazol-2-yl}carbamate
147	methyl (5-{1-hydroxy-3-oxo-2-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
148	but-2-yn-1-yl (5-{1-hydroxy-3-oxo-2-[(1R)-1-phenylethyl]-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
149	N-ethyl-N'-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}urea
150	phenylmethyl (5-{1-hydroxy-3-oxo-2-[(1R)-1-phenylethyl]-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
151	methyl {6-[2-(3-amino-5-chlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
152	piperidin-4-ylmethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
153	methyl {5-[2-(cyclopropylmethyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
154	methyl {5-[2-(2,2-dimethylpropyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
155	methyl {5-[2-(3,5-dichlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
156	methyl {5-[2-(3,5-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
157	N-ethyl-N'-(5-{1-hydroxy-3-oxo-2-[(1R)-1-phenylethyl]-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)urea
158	N'-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-N,N-dimethylurea
159	methyl {5-[2-(3-{[2-(dimethylamino)ethyl]oxy}phenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
160	3-(4-methylpiperazin-1-yl)propyl{6-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
161	methyl {5-[2-(cyclohexylmethyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
162	methyl {5-[1-hydroxy-2-(2-methylpropyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
163	methyl {5-[1-hydroxy-3-oxo-2-(1,3-thiazol-2-ylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
164	methyl {5-[2-(3,4-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
165	methyl (5-{2-[1-(3,5-difluorophenyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
166	methyl (5-{2-[1-(3-fluorophenyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
167	methyl [5-(2-cyclohexyl-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate
168	methyl {5-[2-(2,5-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
169	N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-N'-(phenylmethyl)urea
170	piperidin-4-yl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
171	N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-N'-methylurea
172	methyl (5- {2-[-1-(2-fluorophenyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
173	methyl (5- {1-hydroxy-3-oxo-2-[1-(2-thienyl)ethyl]-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
174	methyl (5-{2-[1-(3-chlorophenyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
175	methyl (5-{1-hydroxy-2-[3-methyl-5-(trifluoromethyl)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
176	N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}propanamide
177	methyl {5-[2-(3,4-dichlorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
178	methyl {5-[2-(3-ethylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
179	methyl {5-[2-(3-ethynylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-I H-benzimidazol-2-yl}carbamate
180	methyl {5-[2-(4-chloro-3-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
181	methyl [5-(1-hydroxy-3-oxo-2-{1-[3-(trifluoromethyl)phenyl]ethyl}-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate
182	methyl (5-{1-hydroxy-3-oxo-2-[(1R)-1-phenylpropyl]-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
183	methyl [5-(1-hydroxy-3-oxo-2-{2-[(trifluoromethyl)oxy]phenyl}-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate
184	methyl{5-[2-(2,3-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
185	cyclohexyl{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
186	tetrahydrofuran-2-ylmethyl{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
187	cyclopropylmethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
188	N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}morpholine-4-carboxamide
189	methyl {5-[2-(cyclopentylmethyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
190	methyl{5-[2-(2,3-dimethylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
191	methyl {5-[2-(2,3-dihydro-1H-inden-1-yl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
192	methyl (2S)-cyclohexyl[1-hydroxy-1-(2-{[(methyloxy)carbonyl]amino}-1H-benzimidazol-5-yl)-3-oxo-1,3-dihydro-2H-isoindol-2-yl]ethanoate
193	methyl {5-[2-(2,6-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
194	methyl {5-[2-(3-chloro-4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
195	but-3-en-1-yl{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
196	2,2,2-trifluoroethyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
197	methyl {5-[2-(5-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
198	methyl {5-{2-[1-(5-chloro-2-methylphenyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
199	methyl (5-{1-hydroxy-3-oxo-2-[(1S)-1-phenylpropyl]-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
200	methyl (5-{2-[1-(3-chloro-2-methylphenyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
201	methyl (5-{1-hydroxy-2-[1-(5-methyl-2-thienyl)ethyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
202	methyl (5-{2-[1-(5-chloro-2-thienyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
203	methyl {5-[1-hydroxy-2-(3-iodophenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
204	methyl (5-{1-hydroxy-2-[3-(1-methylethyl)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
205	methyl{5-[2-(furan-2-ylmethyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
206	methyl {5-[1-hydroxy-3-oxo-2-(3-thienylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
207	methyl {5-[2-(cyclobutylmethyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
208	3,3,3-trifluoro-2-hydroxy-N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-2-(trifluoromethyl)propanamide
209	methyl (5-{1-hydroxy-2-[1-(4-methyl-2-thienyl)ethyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
210	methyl (5-{2-[1-(4-bromo-2-thienyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
211	methyl {5-[1-hydroxy-2-(3-{[2-(methyloxy)ethyl]oxy}phenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
212	tetrahydrofuran-3-ylmethyl{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
213	N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}piperidine-1-carboxamide
214	methyl {5-[2-(3-bromo-4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
215	2,3-dihydroxypropyl{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
216	methyl {5-[1-hydroxy-3-oxo-2-(tetrahydrofuran-2-ylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
217	methyl (5-{2-[3-(aminocarbonyl)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
218	4,4,4-trifluoro-3-hydroxy-N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-3-(trifluoromethyl)butanamide
219	methyl (5-{1-hydroxy-2-[3-(methylsulfonyl)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
220	methyl (5-{1-hydroxy-3-oxo-2-[3-(phenyloxy)phenyl]-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
221	methyl [5-(1-hydroxy-3-oxo-2-{3-[(phenylmethyl)oxy]phenyl}-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate
222	methyl [5-(2-biphenyl-3-yl-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate
223	2,2-dimethyl-3-[(phenylmethyl)oxy]propyl{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
224	methyl{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
225	methyl {5-[2-(3-cyanophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
226	methyl {5-[2-(3-ethynyl-4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
227	methyl {5-[2-(4-fluoro-3-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
228	methyl {6-[2-(3,4-dichloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
229	[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
230	methyl {5-[2-(5-bromo-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
231	methyl (5-{2-[3-(acetylamino)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
232	methyl (5-{1-hydroxy-3-oxo-2-[3-(phenylmethyl)phenyl]-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
233	methyl (5-{2-[1-(4-chloro-2-thienyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
234	methyl (5-{1-hydroxy-3-oxo-2-[3-(phenylcarbonyl)phenyl]-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
235	methyl [5-(2-{3-[(dimethylamino)methyl]phenyl}-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate
236	methyl (5-{2-[3-(aminosulfonyl)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
237	methyl {5-[2-(3-acetylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
238	methyl {5-[2-(3-ethyl-4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
239	methyl {5-[2-(3-chloro-5-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
240	N-{6-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-2-methylpropanamide
241	methyl (5-{2-[1-(3-chloro-2-thienyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
242	methyl [5-(1-hydroxy-3-oxo-2-pyridin-3-yl-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate
243	methyl (5-{1-hydroxy-3-oxo-2-[3-(phenylamino)phenyl]-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
244	methyl {5-[2-(5-bromo-2,4-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
245	methyl {5-[2-(5-chloro-2,4-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
246	methyl {5-[2-(3,5-dichloro-4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
247	2,2-dimethyl-3-(methyloxy)propyl {5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
248	3-hydroxy-2,2-dimethylpropyl{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
249	methyl (5-{2-[1-(5-bromo-2-thienyl)ethyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
250	methyl {5-[2-(4,5-dichloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
251	methyl {5-[2-(3-bromo-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
252	methyl {5-[2-(3-chloro-2,4-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
253	N-{6-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}pent-4-ynamide
254	methyl (6-{1-methyl-3-oxo-2-[3-(trifluoromethyl)phenyl]-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
255	methyl [5-(1-hydroxy-3-oxo-2-{3-[(1,1,2,2-tetrafluoroethyl)oxy]phenyl}-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate
256	methyl {5-[1-hydroxy-3-oxo-2-(3-piperidin-4-ylphenyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
257	methyl {5-[2-(3-ethenylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
258	methyl (5-{2-[3-(dimethylamino)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
259	2,2-difluoro-N-{6-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}cyclopropanecarboxamide
260	N-ethyl-N'-{6-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}urea
261	methyl{5-[2-(3-aminophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
262	N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-4-[(phenylmethyl)oxy]butanamide
263	N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-4-piperidin-1-ylbutanamide
264	N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-4-(4-methylpiperazin-1-yl)butanamide
265	N-{6-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}butanamide
266	methyl {6-[2-(3-bromophenyl)-5,6-dichloro-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
267	methyl [5-(1-hydroxy-2-{3-[methyl(phenyl)amino]phenyl}-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate
268	methyl {5-[1-hydroxy-3-oxo-2-(phenylsulfonyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
269	methyl {5-[(2-{[(phenylamino)carbonyl]amino}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
270	methyl (5-{[2-({[(phenylmethyl)oxy]carbonyl}amino)phenyl]carbonyl}-1H-benzimidazol-2-yl)carbamate
271	methyl [5-({2-[(2-phenylhydrazino)carbonyl]phenyl}carbonyl)-1H-benzimidazol-2-yl]carbamate
272	methyl {5-[(2-{[(phenyloxy)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
273	but-2-yn-1-yl {5-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
274	N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-3-piperidin-1-ylpropanamide
275	N-{6-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}propanamide
276	N-(4-fluorophenyl)-2-{[2-(pent-4-ynoylamino)-1H-benzimidazol-6-yl]carbonyl}benzamide
277	4-(diethylamino)-N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}butanamide
278	N-{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-4-pyrrolidin-1-ylbutanamide
279	3-piperidin-1-ylpropyl{6-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
280	3-(4-methylpiperazin-1-yl)propyl{6-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
281	methyl {5-[2-(3-bromophenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
282	methyl {5-[2-(3-ethynyl-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
283	2-piperidin-1-ylethyl{5-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
284	methyl {5-[2-(3-chloro-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
285	methyl {5-[2-(5-chloro-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
286	N- {6-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-2,2-dimethyl-3-piperidin-1-ylpropanamide
287	N-{5-[2-(4-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-4-piperidin-1-ylbutanamide
288	N- {5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-4-piperidin-1-ylbutanamide
289	methyl [6-({2-[(phenylcarbonyl)amino]phenyl}carbonyl)-1H-benzimidazol-2-yl]carbamate
290	methyl {5-[1-hydroxy-2-(3-morpholin-4-ylphenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
291	2-(dimethylamino)ethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
292	2-(diethylamino)ethyl {5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
293	2-piperidin-1-ylethyl{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
294	3-piperidin-1-ylpropyl{6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
295	2-piperidin-1-ylethyl{6-[2-(3-bromophenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
296	methyl {6-[2-(3-bromophenyl)-4,7-difluoro-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
297	2-[methyl(phenylmethyl)amino]ethyl{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
298	methyl {5-[1-hydroxy-3-oxo-2-(3-pyrrolidin-1-ylphenyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
299	methyl {5-[2-(5-chloro-2,3-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
300	methyl {5-[1-hydroxy-3-oxo-2-(pyrrolidin-2-ylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
301	methyl {5-[1-hydroxy-3-oxo-2-(pyrrolidin-3-ylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
302	(1-methylpiperidin-2-yl)methyl{6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
303	[(2S)-1-methylpyrrolidin-2-yl]methyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
304	octahydro-2H-quinolizin-1-ylmethyl{6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
305	methyl {5-[2-(5-bromo-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
306	5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1,3-dihydro-2H-benzimidazol-2-one
307	methyl {5-[2-(3-bromo-2,5-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
308	2-morpholin-4-ylethyl{6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
309	(1-methylpiperidin-3-yl)methyl{6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
310	methyl (5-{2-[5-chloro-2-(methyloxy)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
311	methyl [5-(2-{3-[cyclohexyl(methyl)amino]phenyl}-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate
312	8-azabicyclo[3.2.1]oct-3-ylmethyl{6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
313	methyl {6-[1-(3-bromophenyl)-5-oxopyrrolidin-2-yl]-1H-benzimidazol-2-yl}carbamate
314	(1-methylpiperidin-4-yl)methyl{5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
315	1,1-dimethylethyl 4-({[({5-[1-hydroxy-3-oxo-2-(phenylmethyl)-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}amino)carbonyl]oxy}methyl)piperidine-1-carboxylate
316	(1-methylpiperidin-4-yl)methyl{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
317	2-(1-methylpiperidin-4-yl)ethyl{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
318	methyl ({6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}amino)(oxo)acetate
319	N-(5-{1-hydroxy-3-oxo-2-[3-(phenyloxy)phenyl]-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)-4-piperidin-1-ylbutanamide
320	methyl{6-[2-(3-bromophenyl)-1-methyl-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
321	4-(diethylamino)but-2-yn-1-yl{6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
322	methyl {5-[2-(3-chloro-2,6-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
323	2-(2-oxopyrrolidin-1-yl)ethyl{6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
324	2-(2,5-dioxopyrrolidin-1-yl)ethyl{6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
325	2,2,3,3-tetrafluorocyclobutyl{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
326	1-acetyl-N-{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}piperidine-4-carboxamide
327	N-{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}cyclobutanecarboxamide
328	methyl [5-(2-{3-[ethyl(phenyl)amino]phenyl}-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl)-1H-benzimidazol-2-yl]carbamate
329	N-{6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-2,2-difluorocyclopropanecarboxamide
330	cyclobutyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
331	2,2-difluoroethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
332	2-(3-chloro-2-fluorophenyl)-3-hydroxy-3-[2-(pyridin-2-ylamino)-1H-benzimidazol-5-yl]-2,3-dihydro-1H-isoindol-1-one
333	1-methylethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
334	cyclopropylmethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
335	N-{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}cyclopropanecarboxamide
336	2-(methyloxy)ethyl{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
337	tetrahydrofuran-2-ylmethyl{6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
338	N-{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-2-(2-thienyl)acetamide
339	methyl {6-[2-(3-chloro-2-fluorophenyl)-4,7-difluoro-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
340	ethyl {6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
341	2-fluoroethyl{6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
342	methyl (5-{1-hydroxy-3-oxo-2-[2-(phenyloxy)phenyl]-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
343	N'-{5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}-N,N-diethylpentanediamide
344	cyclobutylmethyl{6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
345	2,2,2-trifluoroethyl{6-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
346	methyl (5-{2-[3-(1,1-dimethylethyl)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
347	methyl {6-[2-(3-chloro-2-fluorophenyl)-7-fluoro-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
348	2-(3-chloro-2-fluorophenyl)-3-hydroxy-3-[2-(phenylamino)-1H-benzimidazol-5-yl]-2,3-dihydro-1H-isoindol-1-one
349	methyl{6-[4,7-dichloro-2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
350	phenylmethyl 2-[(2-{[(ethyloxy)carbonyl]amino}-1,3-benzoxazol-5-yl)carbonyl]benzoate
351	methyl {5-[2-(5-chloro-3-ethynyl-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
352	methyl {5-[2-(5-ethynyl-2,4-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
353	methyl {5-[2-(3-ethynyl-2,4-difluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
354	2-(3-chloro-2-fluorophenyl)-3-hydroxy-3-[2-(pyrimidin-2-ylamino)-1H-benzimidazol-5-yl]-2,3-dihydro-1H-isoindol-1-one
355	methyl {5-[2-(3-ethynyl-2-fluorophenyl)-4,7-difluoro-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
356	2-(3-chloro-2-fluorophenyl)-3-hydroxy-3-[2-(1,3-thiazol-2-ylamino)-1H-benzimidazol-5-yl]-2,3-dihydro-1H-isoindol-1-one
357	ethyl {5-[2-(3-chloro-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1,3-benzoxazol-2-yl}carbamate
358	methyl {5-[2-(5-chloro-3-iodo-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
359	methyl {5-[2-(3-ethyl-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
360	methyl {5-[2-(5-ethynyl-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
361	2-(3-chloro-2-fluorophenyl)-3-hydroxy-3-[2-(pyrazin-2-ylamino)-1H-benzimidazol-5-yl]-2,3-dihydro-1H-isoindol-1-one
362	methyl {5-[2-(2-fluoro-3-iodophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
363	methyl {6-[2-(5-ethynyl-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
364	2-(3-ethynyl-2-fluorophenyl)-3-hydroxy-3-[2-(pyrimidin-2-ylamino)-1H-benzimidazol-5-yl]-2,3-dihydro-1H-isoindol-1-one
365	methyl {5-[2-(2,5-dimethylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
366	methyl {5-[2-(3-ethenyl-2-fluorophenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
367	methyl (6-{2-[2-fluoro-3-(methyloxy)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
368	methyl (5-{1{1-hydroxy-2-[2-methyl-5-(methyloxy)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
369	methyl {5-[2-(3-ethynyl-2-fluorophenyl)-7-fluoro-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
370	methyl {5-[2-(2-fluoro-3-prop-1-yn-1-ylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
371	methyl {5-[2-(5-chloro-2-methylphenyl)-7-fluoro-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
372	methyl {5-[2-(3-ethynyl-2-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
373	3-hydroxy-2-[3-(methyloxy)phenyl]-3-[2-(pyrimidin-2-ylamino)-1H-benzimidazol-6-yl]-2,3-dihydro-1H-isoindol-1-one
374	3-hydroxy-2-(3-methylphenyl)-3-[2-(pyrimidin-2-ylamino)-1H-benzimidazol-6-yl]-2,3-dihydro-1H-isoindol-1-one
375	2-(5-chloro-2-methylphenyl)-3-hydroxy-3-[2-(pyrimidin-2-ylamino)-1H-benzimidazol-6-yl]-2,3-dihydro-1H-isoindol-1-one
376	methyl {6-[2-(5-chloro-2-methylphenyl)-4,7-difluoro-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
377	methyl {5-[2-(3-ethynyl-2-fluorophenyl)-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
378	2-(3-chloro-2-fluorophenyl)-3-{2-[(6-chloropyridazin-3-yl)amino]-1H-benzimidazol-5-yl}-3-hydroxy-2,3-dihydro-1H-isoindol-1-one
379	2-(3-chloro-2-fluorophenyl)-4,7-difluoro-3-hydroxy-3-[2-(pyrimidin-2-ylamino)-1H-benzimidazol-5-yl]-2,3-dihydro-1H-isoindol-1-one
380	methyl {5-[2-(2-fluoro-5-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
381	methyl (5-{2-[2-fluoro-5-(methyloxy)phenyl]-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
382	methyl (5-{1-hydroxy-2-[5-methyl-2-(methyloxy)phenyl]-3-oxo-2,3-dihydro-1H-isoindol-1-yl}-1H-benzimidazol-2-yl)carbamate
383	methyl {5-[2-(3-ethynyl-5-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
384	2-(3-chloro-2-fluorophenyl)-3-{2-[(5-chloropyrimidin-2-yl)amino]-1H-benzimidazol-5-yl}-3-hydroxy-2,3-dihydro-1H-isoindol-1-one
385	2-(3-chloro-2-fluorophenyl)-3-hydroxy-3-{2-[(4-methylpyrimidin-2-yl)amino]-1H-benzimidazol-5-yl}-2,3-dihydro-1H-isoindol-1-one
386	3-(2-{[4,6-bis(methiloxy)pyrimidin-2-yl]amino}-1H-benzimidazol-5-yl)-2-(3-chloro-2-fluorophenyl)-3-hydroxy-2,3-dihydro-1H-isoindol-1-one
387	2-(3-chloro-2-fluorophenyl)-3-hydroxy-3-(2-{[4-methyl-6-(methyloxy)pyrimidin-2-yl]amino}-1H-benzimidazol-5-yl)-2,3-dihydro-1H-isoindol-1-one
388	3-hydroxy-2-(3-methylphenyl)-3-[2-(pyrazin-2-ylamino)-1H-benzimidazol-6-yl]-2,3-dihydro-1H-isoindol-1-one
389	2-(5-chloro-2-methylphenyl)-3-hydroxy-3-[2-(pyrazin-2-ylamino)-1H-benzimidazol-6-yl]-2,3-dihydro-1H-isoindol-1-one
390	methyl {6-[2-(2-fluoro-3-methylphenyl)-1-hydroxy-3-oxo-2,3-dihydro-1H-isoindol-1-yl]-1H-benzimidazol-2-yl}carbamate
391	3-hydroxy-2-[3-(methyloxy)phenyl]-3-[2-(pyrazin-2-ylamino)-1H-benzimidazol-5-yl]-2,3-dihydro-1H-isoindol-1-one
392	methyl {6-[(2-{[(2-thienylmethyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
393	methyl {6-[(2-{[(3-methylphenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
394	methyl{6-[(2-{[(3-bromophenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
395	methyl {6-[(2-{[(3-chlorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
396	methyl {6-[(2-{[(3-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
397	methyl (6-{[2-({[3-(methyloxy)phenyl]amino}carbonyl)phenyl]carbonyl}-1H-benzimidazol-2-yl)carbamate
398	methyl (6-{[2-({[3-(trifluoromethyl)phenyl]amino}carbonyl)phenyl]carbonyl}-1H-benzimidazol-2-yl)carbamate
399	methyl {6-[(2-{[(3-ethylphenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
400	methyl {6-[(2-{[(3-ethynylphenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
401	methyl {6-[(2-{[(3-chloro-4-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
402	methyl {6-[(2-{[(5-chloro-2-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
403	methyl {6-[(2-{[(3-iodophenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
404	methyl (6-{[2-({[3-(1-methylethyl)phenyl]amino}carbonyl)phenyl]carbonyl}-1H-benzimidazol-2-yl)carbamate
405	methyl {6-[(2-{[(3-thienylmethyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
406	methyl {6-[(2-{[(3-bromo-4-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
407	methyl {6-[(2-{[(3-chloro-2-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
408	methyl {6-[(2-{[(4-fluoro-3-methylphenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
409	methyl {6-[(2-{[(5-bromo-2-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
410	methyl {6-[(2-{[(5-bromo-2,4-difluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
411	methyl {6-[(2-{[(5-chloro-2,4-difluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
412	methyl {6-[(2-{[(3-bromo-2-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
413	methyl {6-[(2-{[(3-ethenylphenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
414	methyl {6-[(2-{[(3-ethynyl-2-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
415	methyl {6-[(2-{[(5-chloro-2-methylphenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
416	methyl {6-[(2-{[(5-bromo-2-methylphenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
417	methyl {6-[(2-{[(2-fluoro-3-iodophenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
418	methyl {6-[(2-{[(3-ethenyl-2-fluorophenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate
419	methyl {6-[(2-{[(2-fluoro-5-methylphenyl)amino]carbonyl}phenyl)carbonyl]-1H-benzimidazol-2-yl}carbamate

Table 7.

Representative EGFR and/or VEGFR Inhibitors

[0237] The Compounds in Table 7 can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 7 can be used.

Entry	Name
1	(3Z)-3-[[5-(methyloxy)-1H-benzimidazol-2-yl](phenyl)methylidene]-5-{[1-(phenylmethyl)pyrrolidin-3-yl]amino}-1,3-dihydro-2H-indol-2-one
2	(3Z)-5-[(1-ethylpiperidin-3-yl)amino]-3-[[5-(methyloxy)-1H-benzimidazol-2-yl](phenyl)methylidene]-1,3-dihydro-2H-indol-2-one
3	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[[5-(methyloxy)-1H-benzimidazol-2-yl](phenyl)methylidene]-1,3-dihydro-2H-indol-2-one
4	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[1H-imidazol-2-yl(phenyl)methylidene]-1,3-dihydro-2H-indol-2-one
5	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-{[5-(methyloxy)-1H-benzimidazol-2-yl][4-(methyloxy)phenyl]methylidene}-1,3-dihydro-2H-indol-2-one
6	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[[5-(methyloxy)-1H-benzimidazol-2-yl](4-methylphenyl)methylidene]-1,3-dihydro-2H-indol-2-one
7	(3Z)-3-[1H-benzimidazol-2-yl(4-nitrophenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
8	(3Z)-3-{1H-benzimidazol-2-yl[4-(methyloxy)phenyl]methylidene}-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
9	(3Z)-3-[1H-benzimidazol-2-yl(phenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
10	(3Z)-3-[[5-(methyloxy)-1H-benzimidazol-2-yl](phenyl)methylidene]-5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
11	(3Z)-3-[(4-aminophenyl)(1H-benzimidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
12	(3Z)-3-[1H-benzimidazol-2-yl(4-methylphenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
13	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[1H-imidazol-2-yl(4-methylphenyl)methylidene]-1,3-dihydro-2H-indol-2-one
14	(3Z)-5-[(1-ethylpiperidin-4-yl)oxy]-3-[[5-(methyloxy)-1H-benzimidazol-2-yl](phenyl)methylidene]-1,3-dihydro-2H-indol-2-one
15	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-{1H-imidazol-2-yl[4-(methyloxy)phenyl]methylidene}-1,3-dihydro-2H-indol-2-one
16	(3Z)-3-[1H-benzimidazol-2-yl(4-fluorophenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
17	(3Z)-3-[1H-benzimidazol-2-yl(3,5-difluorophenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
18	(3Z)-3-[1H-benzimidazol-2-yl(3-fluorophenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
19	(3Z)-3-[1H-benzimidazol-2-yl(3-nitrophenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
20	3-((Z)-1H-benzimidazol-2-yl{5-[(1-ethylpiperidin-4-yl)amino]-2-oxo-1,2-dihydro-3H-indol-3-ylidene}methyl)benzonitrile
21	(3Z)-3-[(3-aminophenyl)(1H-benzimidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
22	(3Z)-3-[1H-benzimidazol-2-yl(phenyl)methylidene]-5-(piperidin-4-ylamino)-1,3-dihydro-2H-indol-2-one
23	3-((Z)-1H-benzimidazol-2-yl{5-[(1-ethylpiperidin-4-yl)amino]-2-oxo-1,2-dihydro-3H-indol-3-ylidene}methyl)benzenecarboximidamide
24	(3Z)-3-[1H-benzimidazol-2-yl(phenyl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
25	(3Z)-3-[1H-benzimidazol-2-yl(phenyl)methylidene]-5-[(2,2,6,6-tetramethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
26	(3Z)-3-{1H-benzimidazol-2-yl[3-(methyloxy)phenyl]methylidene}-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
27	(3Z)-3-[1H-benzimidazol-2-yl(3-chlorophenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
28	2-(2-{2-[(Z)-{5-[(1-ethylpiperidin-4-yl)amino]-2-oxo-1,2-dihydro-3H-indol-3-ylidene}(phenyl)methyl]-1H-imidazol-4-yl}ethyl)-1H-isoindole-1,3(2H)-dione
29	(3Z)-3-[1H-benzimidazol-2-yl(phenyl)methylidene]-5-({1-[2-(dimethylamino)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
30	(3Z)-3-[1H-benzimidazol-2-yl(phenyl)methylidene]-5-{[1-(methylsulfonyl)piperidin-4-yl]amino}-1,3-dihydro-2H-indol-2-one
31	(3Z)-5-(8-azabicyclo[3.2.1]oct-3-ylamino)-3-[1H-benzimidazol-2-yl(phenyl)methylidene]-1,3-dihydro-2H-indol-2-one
32	(3Z)-3-{1H-benzimidazol-2-yl[3-(methyloxy)phenyl]methylidene}-5-[(1-ethylpiperidin-4-yl)oxy]-1,3-dihydro-2H-indol-2-one
33	(3Z)-3-[1H-benzimidazol-2-yl(3,5-difluorophenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)oxy]-1,3-dihydro-2H-indol-2-one
34	(3Z)-3-[1H-benzimidazol-2-yl(phenyl)methylidene]-5-{[1-(phenylmethyl)piperidin-4-yl]oxy}-1,3-dihydro-2H-indol-2-one
35	(3Z)-3-[1H-benzimidazol-2-yl(3-chlorophenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)oxy]-1,3-dihydro-2H-indol-2-one
36	(3Z)-3-[1H-benzimidazol-2-yl(3,5-difluorophenyl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}oxy)-1,3-dihydro-2H-indol-2-one
37	(3Z)-3-[1H-benzimidazol-2-yl(3-chlorophenyl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}oxy)-1,3-dihydro-2H-indol-2-one
38	(3Z)-3-[1H-benzimidazol-2-yl(3-chlorophenyl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
39	(3Z)-3-{1H-benzimidazol-2-yl[3-(methyloxy)phenyl]methylidene}-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
40	(3Z)-3-[(3-chlorophenyl)(1H-imidazol-2-yl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
41	(3Z)-3-[(3-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
42	(3Z)-3-[1H-benzimidazol-2-yl(3,5-difluorophenyl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
43	(3Z)-3-[1H-benzimidazol-2-yl(3-chlorophenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)(methyl)amino]-1,3-dihydro-2H-indol-2-one
44	(3Z)-3-[(3-chlorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)oxy]-1,3-dihydro-2H-indol-2-one
45	(3Z)-3-(1H-benzimidazol-2-yl(4-chlorophenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
46	(3Z)-3-[1H-benzimidazol-2-yl(3-fluorophenyl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
47	(3Z)-3-[1H-benzimidazol-2-yl(4-fluorophenyl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
48	(3Z)-3-[(3-chlorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
49	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(3-fluorophenyl)(1H-imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one
50	(3Z)-3-[1H-benzimidazol-2-yl(3-fluoro-4-methylphenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
51	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(3-fluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one
52	(3Z)-3-[1H-benzimidazol-2-yl(4-fluoro-3-methylphenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
53	(3Z)-3-[(3-chloro-4-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
54	(3Z)-3-[(3,4-difluorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
55	(3Z)-3-[(5-chloro-1H-benzimidazol-2-yl)(phenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
56	(3Z)-3-[(5-chloro-1H-benzimidazol-2-yl)(3,5-difluorophenyl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
57	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(3-fluoro-4-methylphenyl)(1H-imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one
58	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(4-fluorophenyl)(1H-imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one
59	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[1H-imidazol-2-yl(4-propylphenyl)methylidene]-1,3-dihydro-2H-indol-2-one
60	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-{1H-imidazol-2-yl[4-(trifluoromethyl)phenyl]methylidene}-1,3-dihydro-2H-indol-2-one
61	(3E)-3-[(3,5-difluorophenyl)(5-fluoro-1H-benzimidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
62	(3Z)-3-[(3,5-difluorophenyl)(5-fluoro-1H-benzimidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
63	(3Z)-3-[(3-fluoro-4-methylphenyl)(1H-imidazol-2-yl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
64	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(4-methyl-1H-imidazol-2-yl)(4-methylphenyl)methylidene]-1,3-dihydro-2H-indol-2-one
65	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[[3-fluoro-4-(trifluoromethyl)phenyl](1H-imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one
66	(3Z)-3-[(4-chlorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
67	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(3-fluoro-4-methylphenyl)(4-methyl)-1H-imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one
68	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-{1H-imidazol-2-yl[6-(trifluoromethyl)pyridin-3-yl]methylidene}-1,3-dihydro-2H-indol-2-one
69	(3Z)-3-[1H-imidazol-2-yl(4-methylphenyl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
70	(3Z)-3-[(3-fluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
71	(3Z)-3-{1H-imidazol-2-yl[4-(trifluoromethyl)phenyl]methylidene}-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
72	(3Z)-3-[(5-chloro-1H-benzimidazol-2-yl)(phenyl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
73	(3Z)-3-[(3,5-difluorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
74	(3Z)-3-[(3,5-difluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
75	(3Z)-3-[(3,5-difluorophenyl)(1H-imidazol-2-yl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
76	(3Z)-3-[(3,5-difluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
77	(3Z)-3-[(4-methyl-1H-imidazol-2-yl)(4-methylphenyl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
78	(3Z)-3-[(4-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
79	(3Z)-3-[(3,4-difluorophenyl)(1H-imidazol-2-yl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
80	(3Z)-3-[(3-chloro-4-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
81	(3Z)-3-[(3-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-(piperidin-4-ylamino)-1,3-dihydro-2H-indol-2-one
82	(3Z)-3-[(3-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-{[1-(2-piperidin-1-ylethyl)piperidin-4-yl]amino}-1,3-dihydro-2H-indol-2-one
83	(3Z)-3-[(3-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-{[1-(2-morpholin-4-ylethyl)piperidin-4-yl]amino}-1,3-dihydro-2H-indol-2-one
84	(3Z)-5-({1-[2-(diethylamino)ethyl]piperidin-4-yl}amino)-3-[(3-fluorophenyl)(1H-imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one
85	(3Z)-3-[(3-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-{[1-(2-pyrrolidin-1-ylethyl)piperidin-4-yl]amino}-1,3-dihydro-2H-indol-2-one
86	(3Z)-3-[1H-imidazol-2-yl(4-methylphenyl)methylidene]-5-[(1-methylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
87	(3Z)-3-[(3-fuorophenyl)(1H-1,2,4-triazol-5-yl)methylidene]5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
88	ethyl 2-{(Z)-(3-fluorophenyl)[5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-2-oxo-1,2-dihydro-3H-indol-3-ylidene]methyl}-4-methyl-1H-imidazole-5-carboxylate
89	(3Z)-3-[1H-imidazol-2-yl(phenyl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
90	(3Z)-3-{1H-imidazol-2-yl[4-(methyloxy)phenyl]methylidene}-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
91	(3Z)-3-[(4-chlorophenyl)(1H-imidazol-2-yl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
92	(3Z)-3-[[3-fluoro-4-(trifluoromethyl)phenyl](1H-imidazol-2-yl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
93	(3Z)-3-[(3-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-{[1-(methylsulfonyl)piperidin-4-yl]amino}-1,3-dihydro-2H-indol-2-one
94	(3Z)-3-[1H-imidazol-2-yl(4-propylphenyl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
95	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(3-fluorophenyl)(4-phenyl-1H-imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one
96	(3Z)-3-[(3-fluorophenyl)(4-phenyl-1H-imidazol-2-yl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
97	(3Z)-3-[(3-fluoro-4-methylphenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
98	(3Z)-3-{1H-imidazol-2-yl[6-(trifluoromethyl)pyridin-3-yl]methylidene}-5-({1-[2-(methyloxy)ethyl]piperidin-4-yl}amino)-1,3-dihydro-2H-indol-2-one
99	(3Z)-5-[(1-ethylpiperidin4-yl)amino]-3-[(3-fluorophenyl)(1H-1,2,4-triazol-5-yl)methylidene]-1,3-dihydro-2H-indol-2-one
100	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[[2-fluoro-4-(trifluoromethyl)phenyl](1H-imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one
101	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-{(4-methyl-1H-imidazol-2-yl)[4-(trifluoromethyl)phenyl]methylidene}-1,3-dihydro-2H-indol-2-one
102	(3Z)-3-[(4-chlorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
103	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[[3-fluoro-4-(trifluoromethyl)phenyl](4-methyl-1H-imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one
104	(3Z)-3-[(3,4-difluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
105	(3Z)-3-[(3-chloro-4-fluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
106	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(4-fluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one
107	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[(2-fluorophenyl)(1H-imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one
108	(3Z)-5-[(1-ethylpiperidin-4-yl)amino]-3-[[2-fluoro-4-(trifluoromethyl)phenyl](4-methyl-1H-imidazol-2-yl)methylidene]-1,3-dihydro-2H-indol-2-one
109	(3Z)-3-[(2,3-difluorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
110	(3Z)-3-[(2,3-difluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
111	(3Z)-3-[(2,4-difluorophenyl)(4-methy-1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
112	(3Z)-3-[(2,4-difluorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
113	(3Z)-3-[(2-fluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
114	(3Z)-3-[(3-trifluoromethylphenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
115	(3Z)-3-[(3-trifluoromethylphenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin4-yl)amino]-1,3-dihydro-2H-indol-2-one
116	(3Z)-3-[(2,4-dichloro-5-fluorophenyl)(1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
117	(3Z)-3-[(2,4-dichloro-5-fluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one
118	(3Z)-3-[(4-chloro-2-fluorophenyl)(4-methyl-1H-imidazol-2-yl)methylidene]-5-[(1-ethylpiperidin-4-yl)amino]-1,3-dihydro-2H-indol-2-one

Table 8. c-KIT Inhibitors

[0238] The Compounds in Table 8 can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 8 can be used.

Entry	Name
1	N-[5-chloro-2-(methyloxy)phenyl]-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
2	N-phenyl-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
3	N-(2-methylphenyl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy} acetamide
4	N-(2-chlorophenyl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
5	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy} acetamide
6	ethyl 2-[({[3-(1H-tetrazol-1-yl)phenyl]oxy}acetyl)amino]-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxylate
7	N-(3-chloro-2-methylphenyl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy} acetamide
8	N-(3-fluorophenyl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
9	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(2H-tetrazol-5-yl)phenyl]oxy}acetamide
10	N-(4-chloro-2-fluorophenyl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
11	N-(4-bromo-3-methylphenyl)-2- {[3-(1H-tetrazol-1-yl)phenyl]oxy} acetamide
12	N-(4-morpholin-4-ylphenyl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
13	N-[4-fluoro-3-(trifluoromethyl)phenyl]-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
14	N-[4-bromo-3-(trifluoromethyl)phenyl]-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
15	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[4-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
16	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}propanamide
17	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(5-methyl-1H-tetrazol-1-yl)phenyl]oxy}acetamide
18	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[2-methyl-5-(1H-tetrazol-1-yl)phenyl]oxy} acetamide
19	N-(4-chlorophenyl)-N-methyl-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy} acetamide
20	N-[4-chloro-2-(trifluoromethyl)phenyl]-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy} acetamide
21	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(2,5-dioxopyrrolidin-1-yl)phenyl]oxy} acetamide
22	(2E)-N-[4-chloro-3-(trifluoromethyl)phenyl]-3-[3-(1H-tetrazol-1-yl)phenyl]prop-2-enamide
23	N-[4-fluoro-3-(trifluoromethyl)phenyl]-2-{[4-(1H-tetrazol-1-yl)phenyl]oxy} acetamide
24	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(2-methyl-2H-tetrazol-5-yl)phenyl]oxy} acetamide
25	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[2,4-dichloro-5-(1H-tetrazol-1-yl)phenyl]oxy} acetamide
26	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(1H-tetrazol-1-yl)phenyl]thio} acetamide
27	N-[4-chloro-3-(trifluoromethyl)phenyl]-N∼2∼-[3-(1H-tetrazol-1-yl)phenyl]glycinamide
28	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[2-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
29	methyl 1-{3-[(2-{[4-chloro-3-(trifluoromethyl)phenyl]amino}-2-oxoethyl)oxy]phenyl}-1H-1,2,3-triazole-4-carboxylate
30	1,1-dimethylethyl {4-[({[3-(1H-tetrazol-1-yl)phenyl]oxy}acetyl)amino]phenyl}carbamate
31	1,1-dimethylethyl {4-[({[4-(1H-tetrazol-1-yl)phenyl]oxy}acetyl)amino]phenyl}carbamate
32	N-{4-[(1-ethylpiperidin-4-yl)amino]phenyl}-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
33	N-{4-[(1-ethylpiperidin-3-yl)amino]phenyl}-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy} acetamide
34	N-(4-aminophenyl)-2-{[4-(1H-tetrazol-1-yl)phenyl]oxy} acetamide
35	N-{4-[(1-ethylpiperidin-4-yl)amino]phenyl}-2-{[4-(1H-tetrazol-1-yl)phenyl]oxy} acetamide
36	N-{4-[(1-ethylpiperidin-3-yl)amino]phenyl}-2-{[4-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
37	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(3-pyridin-4-ylphenyl)oxy]acetamide
38	N-[4-chloro-3-(trifluoromethyl)phenyl]-N∼2∼-methyl-N∼2∼-[3-(1H-tetrazol-1-yl)phenyl]glycinamide
39	N-1,3-benzothiazol-2-yl-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
40	N-quinolin-8-yl-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
41	N-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
42	N-isoquinolin-5-yl-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
43	N-{3-[(phenylmethyl)oxy]phenyl}-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
44	N-[5-methyl-2-(methyloxy)phenyl]-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
45	N-[2,5-bis(methyloxy)phenyl]-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
46	N-(6-fluoro-1,3-benzothiazol-2-yl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
47	methyl 3-[({[3-(1H-tetrazol-1-yl)phenyl]oxy}acetyl)amino]benzoate
48	5-chloro-2-[({[3-(1H-tetrazol-1-yl)phenyl]oxy}acetyl)amino]benzamide
49	N-[5-chloro-2,4-bis(methyloxy)phenyl]-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy} acetamide
50	N-[2-(phenyloxy)phenyl]-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
51	N-[3-(aminosulfonyl)phenyl]-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
52	N-[2-(methyloxy)-5-(trifluoromethyl)phenyl]-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
53	N-(4-{[(4-methylphenyl)sulfonyl]amino}phenyl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
54	N-(5-phenyl-1H-pyrazol-3-yl)-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
55	N-1,3-benzothiazol-2-yl-2-{[4-(1H-tetrazol-1-yl)phenyl]oxy} acetamide
56	N-quinolin-8-yl-2-{[4-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
57	1,1-dimethylethyl2-{3-[(2-{[4-chloro-3-(trifluoromethyl)phenyl]amino}-2-oxoethyl)oxy]phenyl}-1H-pyrrole-1-carboxylate
58	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(1H-pyrrol-2-yl)phenyl]oxy}acetamide
59	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(3-pyrimidin-5-ylphenyl)oxy]acetamide
60	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-(1H-1,2,3-triazol-1-yl)phenyl]oxy}acetamide
61	4-chloro-N-(2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}ethyl)-3-(trifluoromethyl)aniline
62	N-[4-chloro-3-(trifluoromethyl)phenyl]-N-(2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}ethyl)formamide
63	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(3-pyridin-3-ylphenyl)oxy]acetamide
64	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(3-furan-3-ylphenyl)oxy]acetamide
65	(2E)-N-[4-fluoro-3-(trifluoromethyl)phenyl]-3-[3-(1H-tetrazol-1-yl)phenyl]prop-2-enamide
66	N-[4-fluoro-3-(trifluoromethyl)phenyl]-3-[3-(1H-tetrazol-1-yl)phenyl]propanamide
67	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[6-(1H-tetrazol-1-yl)pyrimidin-4-yl]oxy}acetamide
68	N-[4-chloro-3-(trifluoromethyl)phenyl]-2- {[3-(3,5-dimethylisoxazol-4-yl)phenyl]oxy}acetamide
69	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(3-quinolin-7-ylphenyl)oxy]acetamide
70	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(3-furan-2-ylphenyl)oxy]acetamide
71	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[3-(1H-tetrazol-1-yl)phenyl]hydrazinecarboxamide
72	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(3-dibenzo[b,d]furan-4-ylphenyl)oxy]acetamide
73	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(4-pyrimidin-5-ylphenyl)oxy]acetamide
74	N-methyl-N-[4-(methyloxy)phenyl]-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
75	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-{[3-(1H-tetrazol-1-yl)phenyl]methyl}urea
76	N-[4-chloro-3-(trifluoromethyl)phenyl]-N-methyl-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy} acetamide
77	N-[4-fluoro-3-(trifluoromethyl)phenyl]-N∼2∼-[3-(1H-tetrazol-1-yl)phenyl]glycinamide
78	N-[4-fluoro-3-(trifluoromethyl)phenyl]-2-{[3-(pyridin-2-ylamino)phenyl]oxy}acetamide
79	N-[2-fluoro-5-(trifluoromethyl)phenyl]-2-[3-(1H-tetrazol-1-yl)phenyl]hydrazinecarboxamide
80	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(4-pyridin-3-ylphenyl)oxy]acetamide
81	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-[(3-pyrimidin-5-ylphenyl)methyl]urea
82	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-[(4-pyrimidin-5-ylphenyl)methyl]urea
83	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-[(4-pyridin-3-ylphenyl)methyl]urea
84	[3-(1H-tetrazol-1-yl)phenyl]methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
85	N-[4-fluoro-3-(trifluoromethyl)phenyl]-2-[(4-pyrimidin-5-ylphenyl)oxy]acetamide
86	N∼2∼-[4-chloro-3-(trifluoromethyl)phenyl]-N-[3-(1H-tetrazol-1-yl)phenyl]glycinamide
87	2-{[4-chloro-3-(trifluoromethyl)phenyl]oxy}-N-[3-(1H-tetrazol-1-yl)phenyl]acetamide
88	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-methyl-4-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
89	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[4-(1H-1,2,3-triazol-1-yl)phenyl]oxy}acetamide
90	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[3-fluoro-4-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
91	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
92	N-({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)-3-(1H-tetrazol-1-yl)benzenesulfonamide
93	N-({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)-N-methyl-3-(1H-tetrazol-1-yl)benzenesulfonamide
94	N-[4-fluoro-3-(trifluoromethyl)phenyl]-2-[(4-pyridin-3-ylphenyl)oxy]acetamide
95	2-({4-[2,4-bis(methyloxy)pyrimidin-5-yl]phenyl}oxy)-N-[4-fluoro-3-(trifluoromethyl)phenyl]acetamide
96	2-({4-[2,4-bis(methyloxy)pyrimidin-5-yl]phenyl}oxy)-N-[4-chloro-3-(trifluoromethyl)phenyl]acetamide
97	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[(4-pyridin4-ylphenyl)oxy]acetamide
98	N-[4-chloro-3-(trifluoromethyl)phenyl]-N∼2∼-[3-(methyloxy)-4-(1H-tetrazol-1-yl)phenyl]glycinamide
99	N-[4-chloro-3-(trifluoromethyl)phenyl]-N∼2∼-[4-(methyloxy)-3-(1H-tetrazol-1-yl)phenyl]glycinamide
100	N-[4-chloro-3-(trifluoromethyl)phenyl]-N∼2∼-[4-(1H-tetrazol-1-yl)phenyl]glycinamide
101	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(2,3,5,6-tetrafluoro-4-pyrimidin-5-ylphenyl)hydrazinecarboxamide
102	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-{[4-(1H-tetrazol-1-yl)phenyl]methyl}urea
103	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(4-pyrimidin-5-ylphenyl)hydrazinecarboxamide
104	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-[(3-pyridin-3-ylphenyl)methyl]urea
105	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-methyl-2-{[3-(1H-tetrazol-1-yl)phenyl]oxy}propanamide
106	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[4-(1H-tetrazol-1-yl)phenyl]oxy}propanamide
107	N-({4-[2,4-bis(methyloxy)pyrimidin-5-yl]phenyl}methyl)-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
108	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-({3-[2-(methyloxy)pyrimidin-5-yl]phenyl}methyl)urea
109	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-({3-[6-(methyloxy)pyridin-3-yl]phenyl}methyl)urea
110	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-({4-[2-(methyloxy)pyrimidin-5-yl]phenyl}methyl)urea
111	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-({4-[6-(methyloxy)pyridin-3-yl]phenyl}methyl)urea
112	1,1-dimethylethyl 2-{4-[(2-{[4-chloro-3-(trifluoromethyl)phenyl]amino}-2-oxoethyl)oxy]phenyl}-1H-indole-1-carboxylate
113	N-({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)-4-(1H-tetrazol-1-yl)benzenesulfonamide
114	N-[4-chloro-3-(trifluoromethyl)phenyl]-N∼2∼-[3-(2H-tetrazol-5-yl)phenyl]glycinamide
115	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[2,6-difluoro-4-(1H-tetrazol-1-yl)phenyl]oxy}acetamide
116	(3-pyridin-3-ylphenyl)methyl[4-chloro-3-(trifluoromethyl)phenyl]carbamate
117	(3-pyrimidin-5-ylphenyl)methyl[4-chloro-3-(trifluoromethyl)phenyl]carbamate
118	(3-pyridin-4-ylphenyl)methyl[4-chloro-3-(trifluoromethyl)phenyl]carbamate
119	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-[4-(1H-tetrazol-1-yl)phenyl]hydrazinecarboxamide
120	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(4-pyridin-3-ylphenyl)hydrazinecarboxamide
121	(4-pyridin-3-ylphenyl)methyl[4-chloro-3-(trifluoromethyl)phenyl]carbamate
122	(4-pyridin-4-ylphenyl)methyl[4-chloro-3-(trifluoromethyl)phenyl]carbamate
123	(4-pyrimidin-5-ylphenyl)methyl[4-chloro-3-(trifluoromethyl)phenyl]carbamate
124	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-[(4-pyridin-4-ylphenyl)methyl]urea
125	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(3-pyridin-3-ylphenyl)hydrazinecarboxamide
126	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(3-pyrimidin-5-ylphenyl)hydrazinecarboxamide
127	N-[5-chloro-2,4-bis(methyloxy)phenyl]-N'-[(4-pyrimidin-5-ylphenyl)methyl]urea
128	N-[5-chloro-2,4-bis(methyloxy)phenyl]-N'-[(4-pyridin-3-ylphenyl)methyl]urea
129	(4-pyrimidin-5-ylphenyl)methyl[5-chloro-2,4-bis(methyloxy)phenyl]carbamate
130	(4-pyridin-3-ylphenyl)methyl[5-chloro-2,4-bis(methyloxy)phenyl]carbamate
131	1-(4-pyridin-3-ylphenyl)ethyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
132	1-(4-pyrimidin-5-ylphenyl)ethyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
133	N-[5-chloro-2,4-bis(methyloxy)phenyl]-N'-[(3-pyridin-3-ylphenyl)methyl]urea
134	N-[5-chloro-2,4-bis(methyloxy)phenyl]-N'-[(3-pyrimidin-5-ylphenyl)methyl]urea
135	(3-pyridin-3-ylphenyl)methyl [5-chloro-2,4-bis(methyloxy)phenyl]carbamate
136	(3-pyrimidin-5-ylphenyl)methyl [5-chloro-2,4-bis(methyloxy)phenyl]carbamate
137	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-methyl-2-(3-pyrimidin-5-ylphenyl)hydrazinecarboxamide
138	N-[4-fluoro-3-(trifluoromethyl)phenyl]-N'-[(4-pyridin-3-ylphenyl)methyl]urea
139	N-{[3-(6-aminopyridin-3-yl)phenyl]methyl}-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
140	N-{[4-(6-aminopyridin-3-yl)phenyl]methyl}-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
141	N-{[3-(2-aminopyrimidin-5-yl)phenyl]methyl}-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
142	N-{[4-(2-aminopyrimidin-5-yl)phenyl]methyl}-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
143	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-[1-(4-pyridin-3-ylphenyl)ethyl]urea
144	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-[1-(4-pyrimidin-5-ylphenyl)ethyl]urea
145	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[4-(1H-indol-2-yl)phenyl]oxy} acetamide
146	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(isoquinolin-7-yloxy)acetamide
147	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(4-pyridin-4-ylphenyl)hydrazinecarboxamide
148	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-(3-pyridin-4-ylphenyl)hydrazinecarboxamide
149	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-[(3-pyridin-4-ylphenyl)methyl]urea
150	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-[(3-quinoxalin-6-ylphenyl)methyl]urea
151	methyl 3-amino-6-(3-{[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazi ne-2-carboxylate
152	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-[(4-quinoxalin-6-ylphenyl)methyl]urea
153	N-{[3-(2-amino-5-methylpyridin-3-yl)phenyl]methyl}-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
154	methyl 3-amino-6-(4-{[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazi ne-2-carboxylate
155	[3-(1H-tetrazol-1-yl)phenyl]methyl [3-chloro-4-(methyloxy)phenyl]carbamate
156	N-[3-chloro-4-(methyloxy)phenyl]-N'-{[3-(1H-tetrazol-1-yl)phenyl]methyl}urea
157	N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{[4-(5-hydroxy-1H-tetrazol-1-yl)phenyl]oxy}acetamide
158	N-{[3-(2-amino-5-chloropyridin-3-yl)phenyl]methyl}-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
159	N-{[4-(2-amino-5-chloropyridin-3-yl)phenyl]methyl}-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
160	N-{[3-(6-chloropyridin-3-yl)phenyl]methyl}-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
161	N-{[4-(6-chloropyridin-3-yl)phenyl]methyl}-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
162	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-{[4-(pyrimidin-2-yloxy)phenyl]methyl}urea
163	N-({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)-3-(1H-tetrazol-1-yl)benzamide
164	3-amino-6-(3-{[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-[2-(dimethylamino)ethyl]pyrazine-2-carboxamide
165	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-{[3-(6-fluoropyridin-3-yl)phenyl]methyl}urea
166	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-({3-[2-(methyloxy)pyridin-3-yl]phenyl}methyl)urea
167	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-{[4-(6-fluoropyridin-3-yl)phenyl]methyl}urea
168	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-({4-[2-(methyloxy)pyridin-3-yl]phenyl}methyl)urea
169	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-{[4-(6-methylpyridin-3-yl)phenyl]methyl}urea
170	N-{[4-(2-amino-5-fluoropyridin-3-yl)phenyl]methyl}-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
171	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-{[3-(6-methylpyridin-3-yl)phenyl]methyl}urea
172	N-{[4-(2-aminopyridin-3-yl)phenyl]methyl}-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
173	N-{[3-(2-aminopyridin-3-yl)phenyl]methyl}-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
174	[3-(6-methylpyridin-3-yl)phenyl]methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
175	[3-(2-amino-5-fluoropyridin-3-yl)phenyl]methyl[4-chloro-3-(trifluoromethyl)phenyl]carbamate
176	[3-(2-aminopyridin-3-yl)phenyl]methyl[4-chloro-3-(trifluoromethyl)phenyl]carbamate
177	(3-pyrazin-2-ylphenyl)methyl[4-chloro-3-(trifluoromethyl)phenyl]carbamate
178	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-({3-[6-(hydroxymethyl)pyridin-3-yl]phenyl}methyl)urea
179	N-{[3-(6-acetylpyridin-3-yl)phenyl]methyl}-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
180	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-{[3-(6-cyanopyridin-3-yl)phenyl]methyl}urea
181	1,1-dimethylethyl (3S)-3-({[3-amino-6-(3-{[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazi n-2-yl]carbonyl}amino)piperidine-1-carboxylate
182	3-amino-6-(3-{[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide
183	1,1-dimethylethyl (3S)-3-({[3-amino-6-(4-{[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazi n-2-yl]carbonyl}amino)piperidine-1-carboxylate
184	3-amino-6-(4-{[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-[(3S)-piperidin-3-yl]pyrazine-2-carboxamide
185	[3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
186	N-([3-(2-amino-5-fluoropyridin-3-yl)phenyl]methyl)-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
187	[6-(1H-tetrazol-1-yl)pyridin-2-yl]methyl[4-chloro-3-(trifluoromethyl)phenyl]carbamate
188	[3-(1H-benzimidazol-2-yl)phenyl]methyl[4-chloro-3-(trifluoromethyl)phenyl]carbamate
189	[3-(6-amino-2-methylpyridin-3-yl)phenyl]methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
190	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-({3-[5-(methylthio)pyridin-3-yl]phenyl}methyl)urea
191	[4-(6-methylpyridin-3-yl)phenyl]methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
192	[4-(2-amino-5-fluoropyridin-3-yl)phenyl]methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
193	[4-(2-aminopyridin-3-yl)phenyl]methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
194	(4-pyrazin-2-ylphenyl)methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
195	[4-(7H-pyrrolo[2,3-d]pyrimidin4-yl)phenyl]methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
196	[4-(6-amino-2-methylpyridin-3-yl)phenyl]methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
197	[3-(1H-tetrazol-1-yl)phenyl]methyl 1,3-benzothiazol-2-ylcarbamate
198	[3-(1H-tetrazol-1-yl)phenyl]methyl (5-bromopyridin-2-yl)carbamate
199	(3-pyridin-3-ylphenyl)methyl (3,5-dimethylphenyl)carbamate
200	(3-pyridin-3-ylphenyl)methyl [5-chloro-2-(methyloxy)phenyl]carbamate
201	[4-(1H-tetrazol-1-yl)phenyl]methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
202	(3-pyrimidin-5-ylphenyl)methyl [5-chloro-2-(methyloxy)phenyl]carbamate
203	(4-pyrimidin-5-ylphenyl)methyl (3,4-dimethylphenyl)carbamate
204	(3-pyridin-3-ylphenyl)methyl (3,4-dimethylphenyl)carbamate
205	1,1-dimethylethyl 3-({[3-amino-6-(3-{[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazi n-2-yl]carbonyl}amino)piperidine-1-carboxylate
206	1,1-dimethylethyl 3-({[3-amino-6-(4-{[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazi n-2-yl]carbonyl}amino)piperidine-1-carboxylate
207	3-amino-6-(3-{[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-piperidin-3-ylpyrazine-2-carboxamide
208	3-amino-6-(4-{[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)-N-piperidin-3-ylpyrazine-2-carboxamide
209	1,1-dimethylethyl 4-{[3-amino-6-(3-{[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazi n-2-yl]carbonyl}piperazine-1-carboxylate
210	1,1-dimethylethyl 4-{[3-amino-6-(4-{[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]methyl}phenyl)pyrazi n-2-yl]carbonyl} piperazine-1-carboxylate
211	N-({3-[5-amino-6-(piperazin-1-ylcarbonyl)pyrazin-2-yl]phenyl} methyl)-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
212	N-({4-[5-amino-6-(piperazin-1-ylcarbonyl)pyrazin-2-yl]phenyl}methyl)-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
213	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-{[3-(1H-pyrazol-4-yl)phenyl]methyl}urea
214	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-{[4-(1H-pyrazol-4-yl)phenyl]methyl}urea
215	[3-(2-piperazin-1-ylpyrimidin-5-yl)phenyl]methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
216	[4-(2-piperazin-1-ylpyrimidin-5-yl)phenyl]methyl [4-chloro-3-(tri fluoromethyl)phenyl]carbamate
217	N-{[3-(2-chloropyridin-3-yl)phenyl]methyl}-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
218	N-{[4-(2-chloropyridin-3-yl)phenyl]methyl}-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
219	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-{[3-(2-fluoropyridin-3-yl)phenyl]methyl}urea
220	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-{[4-(2-fluoropyridin-3-yl)phenyl]methyl}urea
221	[3-(1H-tetrazol-1-yl)phenyl]methyl [3-(trifluoromethyl)phenyl]carbamate
222	[3-(1H-tetrazol-1-yl)phenyl]methyl [6-(trifluoromethyl)pyridin-2-yl]carbamate
223	[3-(1H-tetrazol-1-yl)phenyl]methyl [4-(trifluoromethyl)pyridin-2-yl]carbamate
224	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-({3-[5-(methylthio)pyridin-2-yl]phenyl}methyl)urea
225	[3-(2,6-dimethylpyridin-3-yl)phenyl]methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
226	{3-[5-(methyloxy)pyridin-3-yl]phenyl}methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
227	2,3'-bipyridin-6-ylmethyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
228	(6-pyrimidin-5-ylpyridin-2-yl)methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
229	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-[(3-isoquinolin-4-ylphenyl)methyl]urea
230	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-[(4-isoquinolin-4-ylphenyl)methyl]urea
231	[6-(1H-tetrazol-1-yl)pyridin-2-yl]methyl [4-(trifluoromethyl)pyridin-2-yl]carbamate
232	[3-(1H-pyrazol-4-yl)phenyl]methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate
233	[4-(1H-pyrazol-4-yl)phenyl]methyl [4-chloro-3-(trifluoromethyl)phenyl]carbamate

Table 9. c-KIT and/or Flt-3 Inhibitors

[0239] The Compounds in Table 9 can be prepared as pharmaceutically acceptable salts, solvates, hydrates, and/or isomers thereof. All such salt, solvate, hydrate, and isomer combinations of the Compounds in Table 9 can be used.

Entry	Name
1	4-((E)-2-{3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}ethenyl)phenol
2	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-(4-{3-[5-(4-ethylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
3	N-(3-ethylphenyl)-N'-(4-{3-[5-(4-ethylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
4	N-(4-{3-[5-(4-ethylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)-N'-[3-(trifluoromethyl)phenyl]urea
5	N-(3-acetylphenyl)-N'-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
6	N-(3,4-dichlorophenyl)-N'-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
7	N-(3-bromophenyl)-N'-(4-{3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
8	N-[4-fluoro-3-(trifluoromethyl)phenyl]-N'-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
9	N-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)-N'-[4-(phenyloxy)phenyl]urea
10	N-(3-chlorophenyl)-N'-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
11	N-[3,5-bis(methyloxy)phenyl]-N'-(4-{3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
12	N-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)-N'-{4-[(trifluoromethyl)oxy]phenyl}urea
13	N-(4-{3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)-N'-[4-(trifluoromethyl)phenyl]urea
14	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
15	N-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)-N'-[3-(trifluoromethyl)phenyl]urea
16	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-(4-{3-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-5-yl}phenyl)urea
17	N-(3,4-dimethylphenyl)-N'-(4-{5-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-3-yl}phenyl)urea
18	N-(4-chlorophenyl)-N'-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
19	N-(3,5-difluorophenyl)-N'-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
20	N-[3-(methyloxy)phenyl]-N'-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
21	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-(4-{3-[4-(4-ethylpiperazin-1-yl)phenyl]-1H-pyrazol-5-yl}phenyl)urea
22	N-(3-fluorophenyl)-N'-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
23	N-(4-fluorophenyl)-N'-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
24	N-(3-cyanophenyl)-N'-(4-{3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
25	N-(3,4-difluorophenyl)-N'-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
26	N-[3,4-bis(methyloxy)phenyl]-N'-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
27	N-[5-chloro-2-(methyloxy)phenyl]-N'-(4-{5-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-3-yl}phenyl)urea
28	N-(4-{5-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-3-yl}phenyl)-N'-[4-(phenyloxy)phenyl]urea
29	N-(2,4-difluorophenyl)-N'-(4-{3-[6-(4-ethylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
30	N-{4-[3-(1H-benzimidazol-2-yl)-1H-pyrazol-5-yl]phenyl}-N'-[4-chloro-3-(trifluoromethyl)phenyl]urea
31	N-{4-[3-(1H-benzimidazol-2-yl)-1H-pyrazol-5-yl]phenyl}-N'-[2-fluoro-5-(trifluoromethyl)phenyl]urea
32	N-(2,4-difluorophenyl)-N'-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
33	N-{4-[3-(1H-benzimidazol-2-yl)-1H-pyrazol-5-yl]phenyl}-N'-phenylurea
34	N-[3,5-bis(trifluoromethyl)phenyl]-N'-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
35	N-(2-fluorophenyl)-N'-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
36	4-((E)-2-{5-[(E)-2-phenylethenyl]-1H-pyrazol-3-yl}ethenyl)phenol
37	2-(methyloxy)-4-((E)-2-{5-[(E)-2-phenylethenyl]-1H-pyrazol-3-yl}ethenyl)phenol
38	N-(5-fluoro-2-methylphenyl)-N'-(4-{3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
39	N-(4-{3-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)-N'-phenylurea
40	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-(4-{3-[3-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-5-yl}phenyl)urea
41	N-(2,4-difluorophenyl)-N'-(4-{3-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-5-yl}phenyl)urea
42	N-(2,3-dihydro-1,4-benzodioxin-6-yl)-N'-(4-{5-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-3-yl}phenyl)urea
43	N-[2,4-bis(methyloxy)phenyl]-N'-(4-{5-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-3-yl}phenyl)urea
44	4-((E)-2-{3-[(E)-2-(4-fluorophenyl)ethenyl]-1H-pyrazol-5-yl}ethenyl)-2-(methyloxy)phenol
45	4-{(E)-2-[3-(1-benzofuran-2-yl)-1H-pyrazol-5-yl]ethenyl}phenol
46	N-(4-{3-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-5-yl}phenyl)-N'-(2-phenylethyl)ethanediamide
47	4-{(E)-2-[3-(1H-benzimidazol-2-yl)-1H-pyrazol-5-yl]ethenyl}phenol
48	4-((E)-2-{3-[(E)-2-(4-chlorophenyl)ethenyl]-1H-pyrazol-5-yl}ethenyl)-2-(methyloxy)phenol
49	4- {(E)-2-[3-(1-benzothien-2-yl)-1H-pyrazol-5-yl]ethenyl}phenol
50	N-[4-chloro-3-(trifluoromethyl)phenyl]-N'-[4-(3-phenyl-1H-pyrazol-5-yl)phenyl]urea
51	4-((E)-2-{3-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-5-yl}ethenyl)phenol
52	1,1-dimethylethyl{4-[3-(1H-benzimidazol-2-yl)-1H-pyrazol-5-yl]phenyl}carbamate
53	N-(5-fluoro-2-methylphenyl)-N'-(4-{5-[4-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-3-yl}phenyl)urea
54	4-[(E)-2-(3-phenyl-1H-pyrazol-5-yl)ethenyl]phenol
55	2-(methyloxy)-4-[(E)-2-(5-phenyl-1H-pyrazol-3-yl)ethenyl]phenol
56	4-[(E)-2-(5-naphthalen-2-yl-1H-pyrazol-3-yl)ethenyl]phenol
57	4-{(E)-2-[5-(2-fluorophenyl)-1H-pyrazol-3-yl]ethenyl}phenol
58	4-((E)-2-{3-[3-(4-methylpiperazin-1-yl)phenyl]-1H-pyrazol-5-yl}ethenyl)phenol
59	4-((E)-2-{3-[(E)-2-(2,4-difluorophenyl)ethenyl]-1H-pyrazol-5-yl}ethenyl)-2-(methyloxy)phenol
60	4-{(E)-2-[5-(4-fluorophenyl)-1H-pyrazol-3-yl]ethenyl}phenol
61	4-{(E)-2-[3-(4-chlorophenyl)-1H-pyrazol-5-yl]ethenyl}phenol
62	4-[(E)-2-(5-pyridin-2-yl-1H-pyrazol-3-yl)ethenyl]phenol
63	4-{(E)-2-[3-(5-chloro-1-benzofuran-2-yl)-1H-pyrazol-5-yl]ethenyl}phenol
64	N-(1,1-dimethylethyl)-N'-(4-{3-[5-(4-ethylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-5-yl}phenyl)urea
65	4-[(E)-2-(3-pyridin-4-yl-1H-pyrazol-5-yl)ethenyl]phenol
66	4- {(E)-2-[3-(3-chlorophenyl)-1H-pyrazol-5-yl]ethenyl} phenol
67	4-((E)-2-{5-[2-(methyloxy)phenyl]-1H-pyrazol-3-yl}ethenyl)phenol
68	4-{(E)-2-[3-(2-chlorophenyl)-1H-pyrazol-5-yl]ethenyl}phenol
69	4-[(E)-2-(3-pyridin-3-yl-1H-pyrazol-5-yl)ethenyl]phenol
70	4-((E)-2-{5-[3-(methyloxy)phenyl]-1H-pyrazol-3-yl}ethenyl)phenol
71	1,1-dimethylethyl(4-{3-[(E)-2-phenylethenyl]-1H-pyrazol-5-yl}phenyl)carbamate
72	4-{(E)-2-[3-(3,4-dichlorophenyl)-1H-pyrazol-5-yl]ethenyl}phenol
73	2-{5-[(E)-2-phenylethenyl]-1H-pyrazol-3-yl}-1-benzofuran-6-ol
74	4-{(E)-2-[5-(3-fluorophenyl)-1H-pyrazol-3-yl]ethenyl}phenol
75	2-(5-phenyl-1H-pyrazol-3-yl)-1H-benzimidazole
76	N-phenyl-N'-[4-(3-phenyl-1H-pyrazol-5-yl)phenyl]urea
77	4-[3-(1H-benzimidazol-2-yl)-1H-pyrazol-5-yl]aniline
78	4-[(E)-2-(5-biphenyl-3-yl-1H-pyrazol-3-yl)ethenyl]phenol
79	4-((E)-2-{5-[5-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-3-yl}ethenyl)phenol

General Administration

[0240] Also described are pharmaceutical compositions comprising an inhibitor of PI3K as described herein and a pharmaceutically acceptable carrier, excipient, or diluent. In certain other specific options, administration may specifically be by the oral route. Administration of the compounds described herein, or their pharmaceutically acceptable salts, in pure form or in an appropriate pharmaceutical composition, can be carried out via any of the accepted modes of administration or agents for serving similar utilities. Thus, administration can be, for example, orally, nasally, parenterally (intravenous, intramuscular, or subcutaneous), topically, transdermally, intravaginally, intravesically, intracistemally, or rectally, in the form of solid, semi-solid, lyophilized powder, or liquid dosage forms, such as for example, tablets, suppositories, pills, soft elastic and hard gelatin capsules, powders, solutions, suspensions, or aerosols, or the like, specifically in unit dosage forms suitable for simple administration of precise dosages. When treating brain cancers, including glioblastomas, the administration may specifically be by placing a gliadel, a dissolvable material that contains the chemotherapy drug (in particular BCNU), directly into brain tumors during an operation.

[0241] The compositions will include a compound of Formula I or II as the/an active agent and can include a conventional pharmaceutical carrier or excipient and in addition may include other medicinal agents and pharmaceutical agents that are generally administered to a patient being treated for cancer.

[0242] Adjuvants include preserving, wetting, suspending, sweetening, flavoring, perfuming, emulsifying, and dispensing agents. Prevention of the action of microorganisms can be ensured by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, and the like. It may also be desirable to include isotonic agents, for example sugars, sodium chloride, and the like. Prolonged absorption of the injectable pharmaceutical form can be brought about by the use of agents delaying absorption, for example, aluminum monostearate and gelatin.

[0243] If desired, a pharmaceutical composition of the invention may also contain minor amounts of auxiliary substances such as wetting or emulsifying agents, pH buffering agents, antioxidants, and the like, such as, for example, citric acid, sorbitan monolaurate, triethanolamine oleate, butylalted hydroxytoluene, etc.

[0244] The choice of formulation depends on various factors such as the mode of drug administration (e.g., for oral administration, formulations in the form of tablets, pills or capsules) and the bioavailability of the drug substance. Recently, pharmaceutical formulations have been developed especially for drugs that show poor bioavailability based upon the principle that bioavailability can be increased by increasing the surface area i.e., decreasing particle size. For example, U.S. Pat. No. 4,107,288 describes a pharmaceutical formulation having particles in the size range from 10 to 1,000 nm in which the active material is supported on a crosslinked matrix of macromolecules. U.S. Pat. No. 5,145,684 describes the production of a pharmaceutical formulation in which the drug substance is pulverized to nanoparticles (average particle size of 400 nm) in the presence of a surface modifier and then dispersed in a liquid medium to give a pharmaceutical formulation that exhibits remarkably high bioavailability.

[0245] Compositions suitable for parenteral injection may comprise physiologically acceptable sterile aqueous or nonaqueous solutions, dispersions, suspensions or emulsions, and sterile powders for reconstitution into sterile injectable solutions or dispersions. Examples of suitable aqueous and nonaqueous carriers, diluents, solvents or vehicles include water, ethanol, polyols (propyleneglycol, polyethyleneglycol, glycerol, and the like), suitable mixtures thereof, vegetable oils (such as olive oil) and injectable organic esters such as ethyl oleate. Proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersions and by the use of surfactants.

[0246] One specific route of administration is oral, using a convenient daily dosage regimen that can be adjusted according to the degree of severity of the disease-state to be treated.

[0247] Solid dosage forms for oral administration include capsules, tablets, pills, powders, and granules. In such solid dosage forms, the active compound is admixed with at least one inert customary excipient (or carrier) such as sodium citrate or dicalcium phosphate or (a) fillers or extenders, as for example, starches, lactose, sucrose, glucose, mannitol, and silicic acid, (b) binders, as for example, cellulose derivatives, starch, alignates, gelatin, polyvinylpyrrolidone, sucrose, and gum acacia, (c) humectants, as for example, glycerol, (d) disintegrating agents, as for example, agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, croscarmellose sodium, complex silicates, and sodium carbonate, (e) solution retarders, as for example paraffin, (f) absorption accelerators, as for example, quaternary ammonium compounds, (g) wetting agents, as for example, cetyl alcohol, and glycerol monostearate, magnesium stearate and the like (h) adsorbents, as for example, kaolin and bentonite, and (i) lubricants, as for example, talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, or mixtures thereof. In the case of capsules, tablets, and pills, the dosage forms may also comprise buffering agents.

[0248] Solid dosage forms as described above can be prepared with coatings and shells, such as enteric coatings and others well known in the art. They may contain pacifying agents, and can also be of such composition that they release the active compound or compounds in a certain part of the intestinal tract in a delayed manner. Examples of embedded compositions that can be used are polymeric substances and waxes. The active compounds can also be in microencapsulated form, if appropriate, with one or more of the above-mentioned excipients.

[0249] Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups, and elixirs. Such dosage forms are prepared, for example, by dissolving, dispersing, etc., a compound(s) of the invention, or a pharmaceutically acceptable salt or solvate thereof, and optional pharmaceutical adjuvants in a carrier, such as, for example, water, saline, aqueous dextrose, glycerol, ethanol and the like; solubilizing agents and emulsifiers, as for example, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propyleneglycol, 1,3-butyleneglycol, dimethylformamide; oils, in particular, cottonseed oil, groundnut oil, corn germ oil, olive oil, castor oil and sesame oil, glycerol, tetrahydrofurfuryl alcohol, polyethyleneglycols and fatty acid esters of sorbitan; or mixtures of these substances, and the like, to thereby form a solution or suspension.

[0250] Suspensions, in addition to the active compounds, may contain suspending agents, as for example, ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and sorbitan esters, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar-agar and tragacanth, or mixtures of these substances, and the like.

[0251] Compositions for rectal administrations are, for example, suppositories that can be prepared by mixing the compounds of the present invention with for example suitable non-irritating excipients or carriers such as cocoa butter, polyethyleneglycol or a suppository wax, which are solid at ordinary temperatures but liquid at body temperature and therefore, melt while in a suitable body cavity and release the active component therein.

[0252] Dosage forms for topical administration of a compound of this invention include ointments, powders, sprays, and inhalants. The active component is admixed under sterile conditions with a physiologically acceptable carrier and any preservatives, buffers, or propellants as may be required. Ophthalmic formulations, eye ointments, powders, and solutions are also contemplated as being within the scope of this invention.

[0253] Compressed gases may be used to disperse a compound of this invention in aerosol form. Inert gases suitable for this purpose are nitrogen, carbon dioxide, etc.

[0254] Generally, depending on the intended mode of administration, the pharmaceutically acceptable compositions will contain about 1% to about 99% by weight of a compound(s) of the invention, or a pharmaceutically acceptable salt or solvate thereof, and 99% to 1% by weight of a suitable pharmaceutical excipient. In one example, the composition will be between about 5% and about 75% by weight of a compound(s) described herein, or a pharmaceutically acceptable salt or solvate thereof, with the rest being suitable pharmaceutical excipients.

[0255] Actual methods of preparing such dosage forms are known, or will be apparent, to those skilled in this art; for example, see Remington's Pharmaceutical Sciences, 18th Ed., (Mack Publishing Company, Easton, Pa., 1990). The composition to be administered will, in any event, contain a therapeutically effective amount of a compound described herein, or a pharmaceutically acceptable salt or solvate thereof, for treatment of a disease-state in accordance with the teachings of this invention.

[0256] The compounds described herein, or their pharmaceutically acceptable salts, are administered in a therapeutically effective amount which will vary depending upon a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of the compound, the age, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular disease-states, and the host undergoing therapy. The compounds can be administered to a patient at dosage levels in the range of about 0.1 to about 1,000 mg per day. For a normal human adult having a body weight of about 70 kilograms, a dosage in the range of about 0.01 to about 100 mg per kilogram of body weight per day is an example. The specific dosage used, however, can vary. For example, the dosage can depend on a number of factors including the requirements of the patient, the severity of the condition being treated, and the pharmacological activity of the compound being used. The determination of optimum dosages for a particular patient is well known to one of ordinary skill in the art.

[0257] If formulated as a fixed dose, such combination products employ the compounds described herein within the dosage range described above and the other pharmaceutically active agent(s) within its approved dosage range. Compounds described herein may alternatively be used sequentially with known pharmaceutically acceptable agent(s) when a combination formulation is inappropriate.

[0258] Representative pharmaceutical formulations containing a compound of Formula I or II are described below in the Pharmaceutical Composition Examples.

UTILITY

[0259] Certain compounds of Formula I have been tested using the assay described in Biological Example 1 and have been determined to be PI3K inhibitors. As such compounds of Formula I are useful for treating diseases, particularly cancer in which PI3Kactivity contributes to the pathology and/or symptomatology of the disease. For example, cancer in which PI3K activity contributes to its pathology and/or symptomatology include breast cancer, colon cancer, rectal cancer, endometrial cancer, gastric carcinoma, glioblastoma, hepatocellular carcinoma, small cell lung cancer, non-small cell lung cancer, melanoma, ovarian cancer, pancreatic cancer, prostate carcinoma, acute myelogenous leukemia (AML), chronic myelogenous leukemia (CML), and thyroid carcinoma, and the like.
Suitable in vitro assays for measuring PI3K activity and the inhibition thereof by compounds are known. Typically, the assay will measure PI3K-induced ATP consumption. For further details of an in vitro assay for measuring PI3K activity see Biological Examples, Example 1 infra. Cellular activity can be determined using assays as described in Biological Examples 2, 3, and 4 infra. Suitable in vivo models of cancer are known to those of ordinary skill in the art. For further details of in vivo assays see Biological Examples 5-10, infra. Examples describing the administration of a Compound of Formula I in combination with anticancer agents are described in Biological Examples 11-14, infra. Following the examples disclosed herein, as well as that disclosed in the art, a person of ordinary skill in the art can determine what combinations of a Compound of Formula I and anti-cancer agents would be effective for treating cancer.

PREPARATIONS OF THE INTERMEDIATES AND COMPOUNDS OF THE INVENTION

[0260] Compounds described herein can be made by the synthetic procedures described in WO 2007/044729.

[0261] The starting materials and reagents used in preparing these compounds are either available from commercial suppliers such as Aldrich Chemical Co. (Milwaukee, Wis.), or Bachem (Torrance, Calif.), or are prepared by methods known to those skilled
in the art following procedures set forth in references such as Fieser and Fieser's Reagents for Organic Synthesis, Volumes 1-17 (John Wiley and Sons, 1991); Rodd's Chemistry of Carbon Compounds, Volumes 1-5 and Supplementals (Elsevier Science Publishers, 1989); Organic Reactions, Volumes 1-40 (John Wiley and Sons, 1991), March's Advanced Organic Chemistry, (John Wiley and Sons, 4th Edition) and Larock's Comprehensive Organic Transformations (VCH Publishers Inc., 1989). These schemes are merely illustrative of some methods by which the compounds of this invention can be synthesized, and various modifications to these schemes can be made and will be suggested to one skilled in the art having referred to this disclosure. The starting
materials and the intermediates of the reaction may be isolated and purified if desired using conventional techniques, including but not limited to filtration, distillation, crystallization, chromatography and the like. Such materials may be characterized using conventional means, including physical constants and spectral data.

[0262] Unless specified to the contrary, the reactions described herein take place at atmospheric pressure and over a temperature range from about -78 °C to about 150 °C, in another embodiment from about 0 °C. to about 125 °C and most specifically at about room (or ambient) temperature, e.g., about 20 °C. Unless otherwise stated (as in the case of a hydrogenation), all reactions are performed under an atmosphere of nitrogen.

[0263] Prodrugs can be prepared by techniques known to one skilled in the art. These techniques generally modify appropriate functional groups in a given compound. These modified functional groups regenerate original functional groups by routine manipulation or in vivo. Amides and esters of the compounds described herein may be prepared according to conventional methods. A thorough discussion of prodrugs is provided in T. Higuchi and V. Stella, "Pro-drugs as Novel Delivery Systems," Vol 14 of the A.C.S. Symposium Series, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987.

[0264] The compounds for use in the invention, or their pharmaceutically acceptable salts, may have asymmetric carbon atoms or quaternized nitrogen atoms in their structure. Compounds of Formula I that may be prepared through the syntheses described herein may exist as single stereoisomers, racemates, and as mixtures of enantiomers and diastereomers. The compounds may also exist as geometric isomers. Single stereoisomers, racemates and mixtures thereof, and geometric isomers of the compound as claimed in claim 1 may be used within the scope of this invention. Some of the compounds for use in the invention may exist as tautomers. For example, where a ketone or aldehyde is present, the molecule may exist in the enol form; where an amide is present, the molecule may exist as the imidic acid; and where an enamine is present, the molecule may exist as an imine. Such tautomers may be used within the scope of the invention.

[0265] B can be 2-hydroxy-pyridinyl, also described as its structure:

Both 2-hydroxy-pyridinyl and the above structure 14 include, and are equivalent to, pyridin-2(1H)-one and its structure 15:

[0266] Also described are N-oxide derivatives and protected derivatives of compounds of Formula I. For example, when compounds of Formula I contain an oxidizable nitrogen atom, the nitrogen atom can be converted to an N-oxide by methods well known in the art. When compounds of Formula I contain groups such as hydroxy, carboxy, thiol or any group containing a nitrogen atom(s), these groups can be protected with a suitable "protecting group" or "protective group". A comprehensive list of suitable protective groups can be found in T.W. Greene, Protective Groups in Organic Synthesis, John Wiley & Sons, Inc. 1991. The protected derivatives of compounds of Formula I can be prepared by methods well known in the art.

[0267] Methods for the preparation and/or separation and isolation of single stereoisomers from racemic mixtures or non-racemic mixtures of stereoisomers are well known in the art. For example, optically active (R)- and (S)- isomers may be prepared using chiral synthons or chiral reagents, or resolved using conventional techniques. Enantiomers (R- and S-isomers) may be resolved by methods known to one of ordinary skill in the art, for example by: formation of diastereoisomeric salts or complexes which may be separated, for example, by crystallization; via formation of diastereoisomeric derivatives which may be separated, for example, by crystallization, selective reaction of one enantiomer with an enantiomer-specific reagent, for example enzymatic oxidation or reduction, followed by separation of the modified and unmodified enantiomers; or gas-liquid or liquid chromatography in a chiral environment, for example on a chiral support, such as silica with a bound chiral ligand or in the presence of a chiral solvent. It will be appreciated that where a desired enantiomer is converted into another chemical entity by one of the separation procedures described above, a further step may be required to liberate the desired enantiomeric form. Alternatively, specific enantiomer may be synthesized by asymmetric synthesis using optically active reagents, substrates, catalysts or solvents or by converting on enantiomer to the other by asymmetric transformation. For a mixture of enantiomers, enriched in a particular enantiomer, the major component enantiomer may be further enriched (with concomitant loss in yield) by recrystallization.

[0268] In addition, compounds for use in the present invention can exist in unsolvated as well as solvated forms with pharmaceutically acceptable solvents such as water, ethanol, and the like. In general, the solvated forms are considered equivalent to the unsolvated forms for the purposes of the present invention.

[0269] In Compounds of Formula I

the hydrogen on the -NHS(O)₂- group is highly acidic. Thus, intermediates leading to Compounds of Formula I, as well as Compounds of Formula I themselves, can be recovered as uncharged or zwitterionic molecules, or cationic salts such a sodium or potassium, depending on the substitutions on the B ring and on reaction conditions. In the examples that follow, unless otherwise specified, the final form of the compound was assumed to be the uncharged molecule in the absence of analytical techniques that would have determined otherwise.

[0270] Compounds of Formula I can be prepared using methods known to one of ordinary skill in the art. In another embodiment, fusion of appropriate reagents at 180 °C in the presence of a base such as K₂CO₃ and metallic copper is known to provide intermediates of formula I (see S. H. Dandegaonker and C. K. Mesta, J. Med. Chem. 1965, 8, 884).

[0271] Alternatively, the intermediate of formula 3 can be prepared according to the scheme below where each LG^I is a leaving group (in one embodiment halo, in another embodiment chloro) and all other groups are as defined in the Detailed Description of the Invention.

[0272] In scheme 1, an intermediate of formula 3 can be prepared by briefly heating commercially available 2,3-dichloroquinoxaline and an intermediate of formula 2 (which are commercially available or can be prepared by one of ordinary skill in the art), a base such as K₂CO₃, in a solvent, such as DMF or DMSO. Upon completion (about 2 hours), the reaction mixture is then poured into water and followed by 2 N HCl. The product is then extracted into a solvent such as ethyl acetate and washed with water and brine. The organic layers are combined and dried over a drying agent such as sodium sulfate, filtered, and concentrated under vacuum.

[0273] The intermediate of formula 3 is then treated with an intermediate of formula 4 in a solvent such as DMF or p-xylene at reflux temperature. Upon completion of the reaction (about 16 hours or less), the reaction is allowed to cool, extracted into DCM, washed with 2 N HCl and brine, dried over a drying agent such as sodium sulfate or magnesium sulfate, filtered, and concentrated to give a compound of Formula I.

[0274] Alternatively, other methods to prepare quinoxaline derivatives are known to one skilled in the art and include, but are not limited to S. V. Litvinenko, V. I. Savich, D. D. Bobrovnik, Chem. Heterocycl. Compd. (Engl. Transl), 1994, 30, 340 and W. C. Lumma, R. D. Hartman, J. Med. Chem. 1981, 24, 93.

[0275] The following compounds were prepared in a manner similar to that described above.
Example 1: N-(3-{[2,5-bis(methoxy)phenyl]amino}quinoxalin-2-yl)-3-nitrobenzenesulfonamide.
Example 2: N-(3-{[2,5-bis(methoxy)phenyl]amino}quinoxalin-2-yl)-4-chlorobenzenesulfonamide.
Example 3: N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide.
Example 4: 4-chloro-N-(3-chloroquinoxalin-2-yl)benzenesulfonamide.
Example 5: 4-chloro-N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. ¹H NMR (400 MHz, DMSO-d₆) δ 9.18 (s, 1H), 8.78 (s, 1H), 8.40-8.60 (m, 3H), 7.98 (t, 2H), 7.62 (d, 1H), 7.41 (m, 2H), 6.98 (d, 1H), 6.59 (d, 1H), 3.78 (s, 3H), 3.76 (s, 3H); MS (EI) m/z for C₂₂H₁₉N₅O₆S: 482.1 (MH⁺).
Example 6: N-(3-(2,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide. ¹H NMR (400 MHz, CDCl₃) δ 12.68 (br s, 1H), 9.18 (s, 1H), 8.55 (s, 1H), 8.08 (d, 2H), 7.98 (d, 1H), 7.78 (d, 2H), 7.62 (dd, 1H), 7.40 (m, 2H), 7.00 (d, 1H), 6.60 (dd, 1H), 3.78 (s, 6H) ; MS (EI) m/z for C₂₂H₁₉ClN₄O₄S: 471.1 (MH⁺).
Example 7: N-(3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-4-methylphenyl)-2-(dimethylamino)acetamide. ¹H NMR (400 MHz, DMSO-d₆) δ 12.0 (br s, 1 H), 10.6 (s, 1 H), 10.0 (br s, 1 H), 9.52 (s, 1 H), 8.91 (d, 1 H), 8.25 (d, I H), 7.69 (dd, 1H), 7.47 (m, 1 H), 7.39 (d, I H), 7.16 (m, 3 H), 6.01 (dd, 1 H); MS (EI) m/z for C₂₆H₂₇ClN₆O₄S: 555 (MH⁺).

[0276] Compounds of Formula I where B is phenyl substituted with R^3a where R^3a is alkylamino or dialkylamino or B is heteroaryl substituted with R³ where R³ is amino, alkylamino, or dialkylamino, and all other groups are as defined in the Summary of the Invention can be prepared according to Scheme 2.

LG is a leaving group such as chloro. 5 is reacted with NHR^aR^b or HO-C₁-C₆-alkylene-NHR^aR^b where R^a and R^b are independently hydrogen or alkyl. The reaction is carried out in the presence of a base, such as KHCO₃, in a solvent such as DMF.

[0277] Compounds of Formula I where B is phenyl substituted with R^3a where R^3a is aminoalkyloxy, alkylaminoalkyloxy, or dialkylaminoalkyloxy or B is heteroaryl substituted with R³ where R³ is aminoalkyloxy, alkylaminoalkyloxy, or dialkylaminoalkyloxy, and all other groups are as defined in the Summary of the Invention can be prepared according to Scheme 3.

The reaction is carried out in the presence of a base such as NaH in a solvent such as DMF.

[0278] Compounds of Formula I where B is phenyl substituted with R^3a or B is heteroaryl substituted with R³ where R^3a and R³ are

i. -N(R⁷)C(O)-C₁-C₆-alkylene-N(R^7a)(R^7b) where R⁷, R^7a, and R^7b are as defined in the Summary of the Invention;

ii. -NR⁹C(O)R^9a where R⁹ is as defined in the Summary of the Invention;

iii. -NR¹¹C(O)NR^11aR^11b where R^11a, R^11a, and R^11b are as defined in the Summary of the Invention;

iv. -NR¹³C(O)OR^13a where R¹³ and R^13a are as defined in the Summary of the Invention;

v. -N(R¹⁸)C(O)-C₁-C₆-alkylene-N(R^18b)C(O)R^18a where R¹⁸, R^18a, and R^18b are as defined in the Summary of the Invention;

vi. -N(R²⁰)C(O)-C₁-C₆-alkylene-C(O)R^20a where R²⁰ and R^20a as defined in the Summary of the Invention;

vii. -NR²¹S(O)₂-C₁-C₆-alkylene-N(R^21b)R^21a where R²¹, R^21a, and R^21b are as defined in the Summary of the Invention;

viii. -N(R²²)C(O)-C₀-C₆-alkylene-N(R^22b)-N(R^22c)(R^22a), where R²², R^22a and R^22b are as defined in the Summary of the Invention;

ix. -NR²⁴C(O)-C₁-C₆-alkylene-OR²⁴, where R²⁴ and R^24a are as defined in the Summary of the Invention;

and where the alkylene in R³ and R^3a are independently optionally substituted as described in the Summary of the Invention can be prepared according to Scheme 4 by reacting with an intermediate of formula 9(a), 9(b), 9(c), 9(d), 9(e), 9(f), or 9(g):

9((a) HOC(O)-C₁-C₆-alkylene-N(R^7a)(R^7b) where R^a is R^7a or a N-protecting group, such as Boc or Fmoc;

9((b) HOC(O)R^9a;

9((c) HOC(O)NR^11aR^11b;

9((d) HOC(O)OR^13a;

9((e) HOC(O)-C₁-C₆-alkylene-N(R^18b)C(O)R^18a;

9((f) HOC(O)-C₁-C₆-alkylene-C(O)R^20a;

9((g) LG-S(O)₂-C₁-C₆-alkylene-N(R^21b)R^a where R^a is R^21a or a N-protecting group, such as Boc or Fmoc.

R¹⁰⁰ in Scheme 4 is -C(O)R^9a, -C(O)NR^11aR^11b, -C(O)OR^13a, -C(O)-C₁-C₆-alkylene-N(R^18b)C(O)R^18a, -C(O)-C₁-C₆-alkylene-C(O)R^20a, or -S(O)₂-C₁-C₆-alkylene-N(R^21b)R^a. The reaction is carried out under standard amide coupling conditions known to one of ordinary skill in the art. In particular, the reaction is carried out in the presence of a coupling agent such as HATU, a base such as DIEA, and in a solvent such as DMF. Where applicable, the N-protecting group is then removed using procedures known to one of ordinary skill in the art, such as treating with acid where PG is Boc.

[0279] Proceeding as described for Scheme 4, compounds of the invention where B is phenyl substituted with R^3a or B is heteroaryl substituted with R³ where R^3a and R³ are

a) -C(O)NR⁸R^8a;

b) -C(O)N(R¹⁰)-C₁-C₆-alkylene-N(R^10a)R^10b;

c) -C(O)R¹² where R¹² is an N-substituted heterocycloalkyl;

d) -C(O)N(R¹⁴)N(R^14a)(R^14b);

e) -C(O)N(R¹⁶)-C₁-C₆-alkylene-C(O)OR^16a; or

f) -C(O)N(R¹⁹)-C₁-C₆-alkylene-C(O)R^19a; or
can be prepared by exchanging the starting materials as necessary. In particular, the intermediate of formula 11:

is used instead of 8.

[0280] Compounds of Formula I where B is phenyl substituted with R^3a or B is heteroaryl substituted with R³ where R^3a and R³ are -NHC(O)CH₂NR^7aR^7b where R^7a and R^7b are as defined in the Summary of the Invention can be prepared according to Scheme 5.

LG is a leaving group such as bromo or chloro. 12 is reacted with NH(R^7b)R^7a in the presence of a base, such as DIEA, in a solvent such as ACN.

[0281] Compounds of Formula I can be prepared according to Scheme 6.

LG in Scheme 6 is a leaving group such as chloro. The reaction can be carried out by irradiating in a solvent such as DMA. Alternatively, the reaction can be carried out in the presence of acetic acid in a solvent such as DMA and by heating.

Example 8

6-chloro-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)pyridine-3-sulfonamide

[0282] 

[0283] 6-chloropyridine-3-sulfonamide. 6-chloropyridine-3-sulfonyl chloride (4.1 g, 19.3 mmol) was stirred in ammonium hydroxide (30 mL) at room temperature for 2 hr. The reaction mixture was diluted with EtOAc (150 mL) and any insoluble material filtered. The filtrate was transferred to a separatory funnel and the phases were separated. The aqueous phase was further extracted with EtOAc (1 x 15 mL). The combined EtOAc extractions were washed with H₂O (1 x 50 mL) and saturated NaCl (1 x 50 mL), dried over Na₂SO₄, and concentrated in vacuo to give 6-chloropyridine-3-sulfonamide (2.58 g, 69%). MS (EI) m/z for C₅H₅Cl₂N₂O₂S: 190.9 (MH^-).

[0284] 6-chloro-N-(3-chloroquinoxalin-2-yl)pyridine-3-sulfonamide. 2,3-dichloroquinoxaline (1.09 g, 5.48 mmol), 6-chloropyridine-3-sulfonamide (1.05 g, 5.45 mmol), K₂CO₃ (753 mg, 5.45 mmol) and dry DMSO (30 mL) were combined and heated to 150 °C with vigorous stirring for 3-4 hr. The reaction mixture was allowed to cool to room temperature, then poured into 1% AcOH in ice water (300 mL) with vigorous stirring. The resulting solids were filtered, washed with H₂O and dried under high vacuum to give 6-chloro-N-(3-chloroquinoxalin-2-yl)pyridine-3-sulfonamide (1.87g, 96%). MS (EI) m/z for C₁₃H₈Cl₂N₄O₂S: 354.99 (MH⁺).

[0285] 6-chloro-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)pyridine-3-sulfonamide. 6-Chloro-N-(3-chloroquinoxalin-2-yl)pyridine-3-sulfonamide (775 mg, 2.2 mmol), 3,5-dimethoxyaniline (355 mg, 2.3 mmol) and toluene (12 mL) were combined and heated to 125 °C with stirring overnight. The reaction was allowed to cool to room temperature and diluted with Et₂O with vigorous stirring. The resulting solids were filtered, washed with Et₂O and dried to give 6-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)pyridine-3-sulfonamide (920 mg, 89%). ¹H NMR (400 MHz, DMSO-d₆) δ 12.20 (br s, 1H), 9.12 (d, 1H), 9.01 (br s, 1H), 8.53 (dd, 1H), 7.91 (br d, 1H), 7.77 (d, 1H), 7.60 (dd, 1H), 7.40 (m, 4H), 6.26 (m, 1H), 3.78 (s, 6H). MS (EI) m/z for C₂₁H₁₈ClN₅O₄S: 472.0 (MH⁺).

Example 9

N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-6-(2-(dimethylamino)-ethylamino)pyridine-3-sulfonamide

[0286] 

[0287] 6-chloro-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-pyridine-3-sulfonamide (100 mg, 0.21 mmol), prepared using procedures similar to those used in Example 8, KHCO₃ (40 mg, 0.40 mmol), N¹,N¹-dimethylethane-1,2-diamine (225 µL, 2.0 mmol) and dry DMF (1.0 mL) were combined and heated to 130 °C with stirring overnight. The reaction mixture was concentrated in vacuo and purified by preparative HPLC to give N-(3-(3,5-dimethoxy-phenylamino)-quinoxalin-2-yl)-6-(2-(dimethylamino)ethylamino)pyridine-3-sulfonamide (21.0 mg, 19%). ¹H NMR (400 MHz, DMSO-d₆) δ 8.76 (br s, 1H), 8.63 (d, 1H), 8.07 (dd, 1H), 7.40 (m, 1H), 7.34 (m, 1H), 7.28 (d, 2H), 7.14 (m, 4H), 6.47 (d, 1H), 6.12 (m, 1H), 3.75 (s, 6H), 3.35 (m, 2H), 3.14 (m, 2H), 2.74 (s, 6H). MS (EI) m/z for C₂₅H₁₉N₇O₄S: 524.1 (MH⁺).

[0288] Example 10: N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-6-(dimethylamino)pyridine-3-sulfonamide was prepared using procedures similar to those used in Example 9. ¹H NMR (400 MHz, DMSO-d₆) δ 12.00 (br s, 1H), 8.92 (br s, 1H), 8.74 (d, 1H), 8.10 (dd, 1H), 7.38 (br s, 1H), 7.54 (m, 1H), 7.33 (m, 4H), 6.70 (d, 1H), 6.22 (s, 1H), 3.77 (s, 6H), 3.08 (s, 6H). MS (EI) m/z for C₂₃H₂₄N₆O₄S: 481.1 (MH⁺).

Example 11

N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-6-(2-(dimethylamino)-ethoxy)pyridine-3-sulfonamide

[0289] 

[0290] N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)pyridine-3-sulfonamide (100 mg, 0.21 mmol), prepared using procedures similar to those described above in Example 1, 2-(dimethylamino)ethanol (50 µL, 0.50 mmol) and dry DMF were combined and 60% NaH in oil (80 mg, 2.0 mmol) was added. The mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and purified by preparative HPLC to give N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-6-(2-(dimethylamino)ethoxy)pyridine-3-sulfonamide (23 mg, 21%). ¹H NMR (400 MHz, DMSO-d₆) δ 8.78 (d, 1H), 8.73 (s, 1H), 8.38 (dd, 1H), 7.40 (dd, 1H), 7.31 (m, 3H), 7.14 (m, 2H), 6.85 (d, 1H), 6.12 (m, 1H), 4.56 (m, 2H), 3.76 (s, 6H), 3.43 (m, 2H), 2.77 (s, 6H). MS (EI) m/z for C₂₅H₂₈N₆O₅S: 525.1 (MH⁺).

Example 12

N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-6-oxo-1,6-dihydropyridine-3-sulfonamide

[0291] 

[0292] N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)pyridine-3-sulfonamide (220 mg, 0.47 mmol), prepared using procedures similar to those described above in Example 8, DMSO (5 mL), and 3N NaOH (5 mL) are combined and heated to 100 °C overnight with stirring. Upon cooling to room temperature, the reaction mixture was diluted with H₂0 and the pH was adjusted to 7.0 with 1N HCl. The resulting solid was filtered, washed with H₂0, and air-dried. The solid was then sonicated in EtOAc, filtered, washed with EtOAc, and dried under high vacuum to give N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-6-oxo-1,6-dihydropyridine-3-sulfonamide (190 mg, 90%). ¹H NMR (400 MHz, DMSO-d₆) δ 12.23 (br s, 1H), 12.10 (br s, 1H), 8.97 (s, 1H), 8.23 (s, 1H), 7.95 (m, 2H), 7.59 (m, 1H), 7.37 (m, 4H), 6.43 (d, 1H), 6.25 (s, 1H), 3.77 (s, 6H). MS (EI) m/z for C₂₁H₁₉N₅O₅S: 454.0 (MH⁺).
Example 13: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-6-oxo-1,6-dihydropyridine-3-sulfonamide. The title compound was prepared according to the above Example 12. ¹H NMR (400 MHz, DMSO-d₆) δ 12.22 (br s, 1H), 12.10 (br s, 1H), 9.16 (s, 1H), 8.60 (s, 1H), 8.14 (d, 1H), 7.94 (m, 1H), 7.85 (dd, 1H), 7.62 (m, 1H), 7.40 (m, 3H) 6.69 (dd, 1H), 6.43 (d, 1H), 3.81 (s, 3H). MS (EI) m/z for C₂₀H₁₆ClN₅O₄S: 456.0 (MH^-).

Example 14

3-amino-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide.

[0293] 

[0294] N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide. A flask was charged with N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide (5 g, 13.7 mmol), prepared using procedures similar to those in Example 1, 3,5-dimethoxyaniline (4.2 g, 27.4 mmol), and 80 mL of xylene. The reaction mixture was stirred under an N₂ atmosphere at 150 °C for 3 hours, after which time, solvent was removed on a rotary evaporator, and 10 mL of Dichloromethane and 50 mL of methanol were added. The slurry was heated to reflux and filtered while hot, resulting in 4.6 g (69.7 %) of N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide MS (EI) m/z for C₂₂H₁₉N₅O₆S: 482.2 (MH⁺).

Example 153-amino-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide

[0295] 

[0296] A flask was charged with N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-nitro-benzenesulfonamide (3.4g, 7.06 mmol), prepared using procedures similar to those in Example 14, tin chloride solvate (6.4 g, 28.2 mmol), and 30 mL of DMA. A few drops of water were added and the reaction mixture was stirred at 80 °C for 3 hours, after which time, solvent was removed on a rotary evaporator, and 50 mL of water and 10 mL of Methanol were added. The slurry was filtered, and the filtrate was washed with MeOH, water, and diethyl ether (20 mL of each), resulting in 3.25 g 3-amino-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. ¹H NMR (400 MHz, DMSO) δ 12.2 (br s, 1H), 8.85 (s, 1H), 7.90 (br s, 1H), 7.50-7.60 (m, 1H), 7.3-7.4 (m, 4H), 7.2 (m, 3H), 6.74 (m, 1H), 6.24 (m, 1H), 5.56 (br s, 2H), 3.76 (s, 6H). MS (EI) m/z for C₂₂H₂₁N₅O₄S: 452.0 (MH⁺).

[0297] The following compounds were made using procedures similar to those used in Example 15.
Example 16: Proceeding as above, 3-amino-N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide was prepared. ¹H NMR (400 MHz, DMSO) δ 12.4 (br s, 1H), 9.20 (s, 1H), 8.56 (d, 1H), 7.95 (d, 1H), 7.62 (m, 1H), 7.38 (m, 2H), 7.24 (q, 2H), 7.14 (d, 1H), 6.98 (d, I H), 6.8 (m, I H), 6.60 (m, 1H), 5.6 (br s, 2H), 3.78 (d, 6H). MS (EI) m/z for C₂₂H₂₁N₅O₄S: 452.3 (MH⁺).
Example 17: Proceeding as above, 3-amino-N-(3-(2-chloro-5-hydroxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide was prepared. MS (EI) m/z for C₂₀H₁₆ClN₅O₃S 1.0 x C₂H₁O₂F₃: 442.2, 444.2 (MH⁺).
Example 18: Proceeding as above, 3-amino-N-(3-(6-methoxyquinolin-8-ylamino)quinoxalin-2-yl)benzenesulfonamide was prepared. MS (EI) m/z for C₂₄H₂₀N₆O₃S: 473.0 (MH⁺).
Example 19: 3-amino-N-(3-(3-fluoro-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₁H₁₈FN₅O₃S: 439.99 (MH⁺).
Example 20: 3-amino-N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₁H₁₈ClN₅O₃S: 457.02 (MH⁺).
Example 21: 3-amino-N-(3-(5-methoxy-2-methyl-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₂H₂₁N₅O₃S: 436.32 (MH⁺).

Example 22a and Example 22b

3-amino-N-(3-(3-methoxy-5-nitro-phenylamino)quinoxalin-2-yl)benzenesulfonamide and 3-amino-N-(3-(3-amino-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide

[0298] 

[0299] To a mixture of N-(3-{[3-(methyloxy)-5-nitrophenyl]amino}quinoxalin-2-yl)-3-nitrobenzenesulfonamide (400 mg), THF (2 mL) and EtOH (2 mL) was added formic acid (938 µL), potassium formate (203 mg). After the mixture was flushed with N₂, 10%wt Pd/C (50 mg) was added. The resulting mixture was heated at 60 °C with stirring. LC/MS analysis indicated that the reaction mixture contained the complete reduced diamino compound as the major product and the partially reduced mono-amino compound as a minor product. A portion of the crude mixture was purified by HPLC to give the two products. Product A: 3-amino-N-(3-(3-methoxy-5-nitro-phenylamino)quinoxalin-2-yl)benzenesulfonamide. ¹H NMR (400 MHz, DMSO) δ 12.2 (br s, 1H), 9.51 (s, 1H), 8.77 (s, 1H), 8.21 (s, 1H), 7.92 (s, 1H), 7.48 (m, 1H), 7.43-7.38 (m, 3H), 7.24-7.16 (m, 3H), 6.75 (d, 1H), 5.57 (br s, 2H), 3.90 (s, 3H). MS (EI) for C₂₁H₁₈N₆O₅S: 467.00 (MH+). Product B: 3-amino-N-(3-(3-amino-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. ¹H NMR (400 MHz, DMSO) δ 12.0 (br. s, 1H), 8.53 (s, 1H), 7.84 (s, 1H), 7.56 (d, 1H), 7.37-7.30 (m, 2H), 7.21-7.17 (m, 3H), 6.87 (s, 1H), 6.81 (s, 1H), 6.74 (br s, 2H), 5.91 (s, 1H), 5.56 (br s, 3H), 3.69 (s, 3H). MS (EI) for C₂₁H₂₀N₆O₃S: 437.2 (MH+).

Example 23a and Example 23b

N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-(hydroxyamino)-benzenesulfonamide and 3-amino-N-(3-{[3,5-(dimethoxy)phenyl]amino}quinoxalin-2-yl)benzenesulfonamide

[0300] 

[0301] To a solution N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide (1.3g) in 20 mL of THF and 10 mL of MeOH was added 10%wt Pd/C (100 mg). The mixture was stirred under a H₂ balloon overnight. A portion of the reaction mixture was taken out and filtered, then purified by HPLC to afford two products. Product A: N-(3-{[3,5-bis(methyloxy)phenyl]amino}quinoxalin-2-yl)-3-(hydroxyamino)benzenesulfonamide. MS (EI) for C₂₂H₂₁N₅O₅S: 468.1 (MH⁺). Product B: 3-amino-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. ¹H NMR (400 MHz, DMSO) δ 12.2 (br s, 1H), 8.85 (s, 1H), 7.90 (br s, 1H), 7.50-7.60 (m, 1H), 7.3-7.4 (m, 4H), 7.2 (m, 3H), 6.74 (m, 1H), 6.24 (m, 1H), 5.56 (br s, 2H), 3.76 (s, 6H). MS (EI) for C₂₂H₂₁N₅O₄S: 452.0 (MH⁺).

Example 24

(S)-2-amino-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)propanamide hydrochloride.

[0302] 

[0303] (S)-tert-butyl 1-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenylamino)-1-oxopropan-2-ylcarbamate. 3-amino-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide (1.1 mmol, 500 mg), prepared using procedures similar to those described above in Example 15, (L)-Boc-Ala-OH (1.5 mmol, 284 mg), dichloromethane (15 mL), DMF (10 mL), DIEA (2 mmol, 330 µL), and HATU (2 mmol, 760 mg) stirred at room temperature over night. The crude mixture was column purified using 1/1 ethyl acetate/hexanes on silica to gave 160 mg.

[0304] (S)-2-amino-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)propanamide hydrochloride. 4 N HCl is dioxane (10 mL) was added to a solution of (S)-tert-butyl 1-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenylamino)-1-oxopropan-2-ylcarbamate (160 mg) and DCM (15 mL). The mixture was stirred at room temperature for 3 hours. The solvent decanted and ether added to the solid, ether decanted to gave 80 mg product as HCl salt. ¹H NMR (400 MHz, CD₃OD) δ 8.50-8.49 (t, 1H), 7.89-7.87 (m, 1H), 7.74-7.72 (m, 1H), 7.61-7.5 (m, 3H), 7.40-7.36 (m, 2H), 7.21-7.20 (d, 2H), 6.23-6.21 (t, 1H), 4.09-4.03 (q, 1H), 3.78 (s, 6H), 1.60-1.58 (d, 3H); MS (EI) m/z for C₂₅H₂₆N₆O₅S·HCl: 523.1 (MH⁺).

[0305] The following compounds were prepared as the free amine and/or HCl salt using procedures similar to those in Example 24. Where the deprotection step is not necessary, Step B in the above scheme was not preformed.
Example25: N-(2-chloro-5-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)acetamide. The title compound was prepared according to the Examples above. ¹H NMR (400 MHz, DMSO-d₆) δ 10.50 (s, 1H), 9.14 (s, 1H), 9.03 (m, 2H), 8.63 (d, 1H), 8.44 (d, 1H), 7.98 (m, 1H), 7.91 (dd, 1H), 7.80 (d, 1H), 7.67 (m, 1H), 7.44 (m, 3H), 6.71 (dd, 1H), 4.06 (m, 2H), 3.83 (s, 3H), 2.64 (t, 3H). MS (EI) m/z for C₂₄H₂₂Cl₂N₆O₄S: 561.0 (MH⁺).
Example 26: (S)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamlno)quinoxalin-2-yl)sulfamoyl)phenyl)propanamide hydrochloride. ¹H NMR (400 MHz, CD₃OD) δ 8.72-8.71 (d, 1H), 8.48-8.46 (t, 1H), 7.86-7.84 (m, 1H), 7.80-7.78 (m, 1H), 7.63-7.59 (m, 2H), 7.58-7.55 (t, 1H), 7.41-7.38 (m, 2H), 7.24-7.22 (d, 1H), 6.60-6.58 (dd, 1H), 4.10-4.04 (q, 1H), 3.83 (s, 3H), 1.61-1.60 (d, 3H); MS (EI) m/z for C₂₄H₂₃ClN₆O₄S·HCl: 527.2 (MH⁺).
Example 27: (S)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)butanamide hydrochloride. ¹H NMR (400 MHz, CD₃OD) δ 8.74-8.73 (d, 1H), 8.80-8.47 (t, 1H), 7.87-7.85 (m, 1H), 7.80-7.78 (m, 1H), 7.67-7.61 (m, 2H), 7.59-7.55 (t, 1H), 7.42-7.39 (m, 2H), 7.26-7.24 (d, 1H), 6.62-6.59 (dd, 1H), 3.96-3.93 (t, 1H), 3.84 (s, 3H), 2.02-1.94 (m, 2H, 1.09-1.06 (t, 3H); MS (EI) m/z for C₂₅H₂₅ClN₆O₄S·HCl: 541.3 (MH⁺).
Example 28: (S)-N-(3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pyrrolidine-2-carboxamide hydrochloride. ¹H NMR (400 MHz, CD₃OD) δ 8.78-8.77 (d, 1H), 8.47-8.46 (t, 1H), 7.87-7.85 (m, 1H), 7.80-7.75 (m, 1H), 7.69-7.65 (m, 2H), 7.59-7.55 (t, 1H), 7.45-7.41 (m, 2H), 7.31-7.28 (d, 1H), 6.65-6.63 (dd, 1H), 4.42-4.38 (m, 1H), 3.86 (s, 3H), 3.48-3.42 (m, 2H), 2.55-2.49 (m, 1H), 2.18-2.08 (m, 3H); MS (EI) m/z for C₂₆H₂₅ClN₆O₄S·HCl: 553.3 (MH⁺).
Exmaple 29: (S)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pyrrolidine-2-carboxamide hydrochloride. ¹H NMR (400 MHz, CD₃OD) δ 10.62 (br s, 1H), 8.50-8.49 (t, 1H), 7.90-7.87 (m, 1H), 7.76-7.73 (m, 1H), 7.63-7.58 (m, 3H), 7.43-7.35 (m, 2H), 7.14 (s, 2H), 6.27-6.26 (t, 1H), 4.43-4.38 (m, 1H), 3.78 (s, 6H), 3.48-3.41 (m, 1H), 3.40-3.36 (m, 1H(, 2.54-2.48 (m, 1H), 2.19-2.05 (m, 3H); MS (EI) m/z for C₂₇H₂₈N₆O₅S·HCl: 549.3 (MH⁺).
Example 30: (R)-2-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-hydroxypropanamide hydrochloride. ¹H NMR (400 MHz, CD₃OD) δ 8.49-8.48 (t, 1H), 7.89-7.87 (m, 1H), 7.75-7.72 (m, 1H), 7.65-7.62 (m, 2H), 7.62-7.55 (t, 1H), 7.44-7.38 (m, 2H), 7.23-7.22 (d, 2H), 6.27-6.26 (t, 1H), 4.07-4.05 (m, 1H), 3.99-3.93 (m, 2H), 3.80 (s, 6H); MS (EI) m/z for C₂₅H₂₆N₆O₆S·HCl: 539.1 (MH⁺).
Example 31: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)piperidine-3-carboxamide hydrochloride. ¹H NMR (400 MHz, CD₃OD) δ 8.79-8.78 (d, 1H), 8.45 (m, 1H), 7.83-7.81 (d, 1H), 7.76-7.74 (m, 1H), 7.636 (m, 2H), 7.54-7.50 (t, 1H), 7.41 (m, 2H), 7.30-7.28 (d, 1H), 6.65-6.62 (dd, 1H), 3.86 (s, 3H), 3.40-3.32 (m, 2H), 3.20-3.13 (m, 3H), 2.93 (m, 1H), 2.15-2.11 (m, 1H), 1.98-1.93 (m, 2H), 1.83 (m, 1H); MS (EI) m/z for C₂₇H₂₇ClN₆O₄S·HCl: 567.3 (MH⁺). Example32: (S)-2-amino-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)butanamide hydrochloride. MS (EI) m/z for C₂₆H₂₈N₆O₅S·HCl: 537.1 (MH⁺).
Example 33: (R)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pyrrolidine-2-carboxamide hydrochloride. MS (EI) m/z for C₂₇H₂₈N₆O₅S·HCl: 549.1 (MH⁺).
Example 34: (R)-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pyrrolidine-2-carboxamide hydrochloride. MS (EI) m/z for C₂₆H₂₅ClN₆O₄S·HCl: 553 (MH⁺).
Example 35: (R)-2-amino-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)propanamide. ¹H NMR (400 MHz, DMSO-d₆) δ 10.2 (br s, 1 H), 8.82 (s, I H), 8.27 (m, 1 H), 7.75 (m, 2 H), 7.33 (m, 5 H), 7.13 (m, 2 H), 6.14 (t, I H), 3.77 (s, 6 H), 1.39 (d, 3 H); MS (EI) m/z for C₂₅H₂₆N₆O₅S: 523 (MH⁺).
Example 36:N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)acetamide. ¹H NMR (400 MHz, DMSO-d₆) δ 10.6 (s, 1 H), 9.48 (s, 1 H), 8.95 (br s, I H), 8.75 (br s, I H), 8.19 (br s, 1 H), 7.77 (dd, I H), 7.69 (dd, 1 H), 7.41 (m, 4 H), 7.17 (m, 2 H), 6.60 (dd, I H), 3.91 (s, 2 H), 3.82 (s, 6 H), 2.62 (s, 3 H); MS (EI) m/z for C₂₄H₂₃ClN₆O₄S: 527 (MH⁺).
Example 37: (R)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)propanamide. ¹H NMR (400 MHz, DMSO-d₆) δ 10.5 (s, 1 H), 9.47 (s, I H), 8.95 (d, I H), 8.22 (d, 2 H), 8.14 (br s, 2 H), 7.76 (m, 2 H), 7.40 (m, 4 H), 7.17 (m, 2 H), 6.60 (m, 1 H), 3.97 (q, 1 H), 3.96 (s, 3 H), 1.45 (d, 3 H); MS (EI) m/z for C₂₄H₂₃ClN₆O₄S: 527 (MH⁺).
Example 38: 2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylpropanamide. ¹H NMR (400 MHz, DMSO-d₆) δ 10.1 (s, 1 H), 9.46 (s, I H), 8.95 (d, 1 H), 8.50 (br s, 1 H), 8.27 (m, 1 H), 7.81 (m, 2 H), 7.47 (m, 1H), 7.37 (m, 3 H), 7.17 (m, 2 H), 6.61 (dd, 1 H), 3.83 (s, 3 H), 1.60 (s, 6 H); MS (EI) m/z for C₂₅H₂₅ClN₆O₄S: 541 (MH⁺).
Example 39: 2-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylpropanamide. ¹H NMR (400 MHz, DMSO-d₆) δ 10.33 (s, I H), 8.89 (s, 1 H), 8.32 (br s, 4 H), 7.92 (m, 3 H), 7.59 (m, 2 H), 7.37 (m, 4 H), 6.24 (s, 1 H), 3.76 (s, 6 H), 1.61 (s, 6 H); MS (EI) m/z for C₂₆H₂₈N₆O₅S: 537 (MH⁺).
Example 40: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-4-methylphenyl)-2-(dimethylamino)acetamide. ¹H NMR (400 MHz, DMSO-d₆) δ 10.58 (s, 1 H), 9.80 (br s, 1 H), 8.85 (s, 1 H), 8.25 (s, 1 H), 7.67 (dd, 1 H), 7.30 (m, 7 H), 6.16 (m, 1 H), 4.02 (br s, 2 H), 3.77 (s, 6 H), 2.81 (s, 6 H), 2.54 (s, 3 H); MS (EI) m/z for C₂₇H₃₀N₆O₅S: 551 (MH⁺).
Example 41: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-((2-(dimethylamino)ethyl)(methyl)amino)acetamide. ¹H NMR (400 MHz, DMSO-d₆) δ 10.0 (s, I H), 9.48 (s, 1 H), 8.96 (d, 1 H), 8.16 (m, 1 H), 7.76 (m, 2 H), 7.39 (m, 4 H), 7.17 (m, 2 H), 6.61 (dd, I H), 3.82 (s, 3 H), 3.40 (br s, 2 H), 2.94 (br s, 2 H), 2.71 (br t, 2 H), 2.60 (s, 6 H), 2.33 (s, 3 H); MS (EI) m/z for C₂₈H₃₂ClN₇O₄S: 598 (MH⁺).
Example 42: 2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. ¹H NMR (400 MHz, DMSO-d₆) δ 10.5 (s, 1 H), 9.48 (s, 1 H), 8.94 (s, 1 H), 8.15 (s, 1 H), 8.06 (br s, 3 H), 7.74 (m, 2 H), 7.39 (m, 4 H), 7.18 (m, 2 H), 6.61 (dd, I H), 3.83 (s, 3 H), 3.77 (s, 2 H); MS (EI) m/z for C₂₃H₂₁ClN₆O₄S: 513 (MH⁺).
Example 43: N-(3-(N-(3-(2-acetyl-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide. ¹H NMR (400 MHz, DMSO-d₆) δ 12.4 (s, 1 H), 10.5 (s, 1 H), 9.27 (s, 1 H), 8.25 (s, I H), 8.01 (d, 1 H), 7.82 (d, 1 H), 7.71 (d, 1 H), 7.42 (m, 3 H), 7.21 (m, 2 H), 6.63 (dd, 1H),3.91 (m, 5 H), 2.75 (s, 6 H), 2.61 (s, 3 H); MS (EI) m/z for C₂₇H₂₈N₆O₅S: 549 (MH⁺).
Example 44: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)formamide. ¹H NMR (400 MHz, DMSO-d₆) δ 12.6 (s, 1 H), 10.5 (s, 1 H), 9.16 (s, 1 H), 8.53 (br s, 1 H), 8.35 (m, 2 H), 8.02 (s, 1 H), 7.56 (m, 7 H), 6.70 (dd, 1 H), 3.83 (s, 3 H); MS (EI) m/z for C₂₂H₁₈ClN₅O₄S: 484 (MH⁺).
Example 45: 2-amino-N-(5-(N-(3-(3,5-dlmethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-2-methylphenyl)acetamide. ¹H NMR (400 MHz, DMSO-d₆) δ 12.4 (s, 1 H), 10.1 (br s, 1 H), 8.82 (s, I H), 8.20 (m, 3 H), 7.82 (m, 1 H), 7.30 (m, 6 H), 6.20 (s, 1 H), 3.85 (s, 2 H), 3.77 (s, 6 H), 2.26 (s, 3 H); MS (EI) m/z for C₂₅H₂₆N₆O₅S: 523 (MH⁺).
Example 46: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methyl-2-(methylamino)propanamide. ¹H NMR (400 MHz, DMSO-d₆) δ 10.09 (s, 1 H), 9.46 (s, 1 H), 8.95 (m, 3 H), 8.28 (s, 1 H), 7.81 (m, 2 H), 7.41 (m, 4 H), 7.17 (m, 2 H), 6.60 (dd, 1 H), 3.82 (s, 3 H), 2.53 (s, 3 H), 1.60 (s, 6 H); MS (EI) m/z for C₂₆H₂₇ClN₆O₄S: 555 (MH⁺).
Example 47: (S)-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)propanamide. ¹H NMR (400 MHz, DMSO-d₆) δ 10.61 (s, 1 H), 9.47 (s, 1 H), 8.95 (s, 1 H), 8.82 (br s, 2 H), 8.27 (m, I H), 7.74 (m, 2 H), 7.42 (m, 4 H), 7.17 (m, 2 H), 6.60 (dd, I H), 3.90 (m, 1 H), 3.82 (s, 3 H), 2.59 (s, 3 H), 1.49 (d, 3 H); MS (EI) m/z for C₂₅H₂₅ClN₆O₄S: 541 (MH⁺).
Example 48: 3-amino-N-(5-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-2-methylphenyl)propanamide. ¹H NMR (400 MHz, DMSO-d₆) δ 12.25 (s, 1 H), 9.77 (s, I H), 8.82 (s, I H), 7.84 (m, 5 H), 7.50 (d, 1 H), 7.37 (m, 5 H), 6.22 (m, I H), 3.74 (s, 6 H), 3.08 (m, 2 H), 2.77 (m, 2 H), 2.27 (s, 3 H); MS (EI) m/z for C₂₆H₂₈N₆O₅S: 537 (MH⁺).
Example 49: 1-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)cyclopropanecarboxamide. ¹H NMR (400 MHz, DMSO-d₆) δ 9.54 (br s, 1 H), 9.42 (s, 1 H), 8.91 (s, 1 H), 8.21 (s, 1 H), 8.20 (br s, 2 H), 7.81 (m, 2 H), 7.48 (m, 4 H), 7.22 (m, 2 H), 6.61 (dd, 1 H), 3.82 (s, 3 H), 1.63 (m, 2 H), 1.26 (m, 2 H); MS (EI) m/z for C₂₅H₂₃ClN₆O₄S: 539 (MH⁺).
Example 50: (S)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-6-(dimethylamino)hexanamide. ¹H NMR (400 MHz, DMSO-d₆) δ 9.47 (br s, 1 H), 8.95 (d, 1 H), 8.26 (m, 1 H), 7.73 (m, 2 H), 7.30 (m, 4 H), 7.26 (m, 4 H), 7.16 (m, 2 H), 6.59 (dd, 1 H), 3.82 (s, 3 H), 3.34 (m, 1 H), 2.20 (m, 2 H), 2.09 (s, 6 H), 1.50 (m, 6 H); MS (EI) m/z for C₂₉H₃₄ClN₇O₄S: 610 (MH⁺).
Example 51: 1-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)cyclopentanecarboxamide. ¹H NMR (400 MHz, DMSO-d₆) δ 10.12 (br s, 1 H), 9.46 (s, 1 H), 8.95 (d, 1 H), 8.26 (m, 1 H), 8.16 (m, 3 H), 7.84 (m, 2 H), 7.35 (m, 6 H), 6.60 (dd, 1 H), 3.82 (s, 3 H), 2.34 (m, 2 H), 1.91 (m, 6 H); MS (EI) m/z for C₂₇H₂₇ClN₆O₄S: 567 (MH⁺).
Example 52: N-(5-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-2-methylphenyl)-2-(dimethylamino)acetamide. ¹H NMR (400 MHz, DMSO-d₆) δ 12.0 (br s, 1 H), 9.98 (s, I H), 9.43 (s, 1 H), 8.91 (m, 1 H), 8.08 (s, I H), 7.84 (dd, 1 H), 7.32 (m, 6 H), 6.61 (dd, 1 H), 4.07 (s, 2 H), 3.82 (s, 3 H), 2.82 (s, 6 H), 2.21 (s, 3 H); MS (EI) m/z for C₂₆H₂₇ClN₆O₄S: 555 (MH⁺).
Example 53: 1-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)cyclobutanecarboxamide. ¹H NMR (400 MHz, DMSO-d₆) δ 10.34 (br s, 1 H), 8.81 (s, 1 H), 8.49 (br s, 3 H), 8.34 (s, 1 H), 7.83 (m, 2 H), 7.43 (m, 3 H), 7.31 (m, 2 H), 7.16 (m, 2 H), 6.16 (s, 1 H), 3.77 (s, 6 H), 2.83 (m, 2 H), 2.25 (m, 3 H), 2.05 (m, 1 H); MS (EI) m/z for C₂₇H₂₈N₆O₅S: 549 (MH⁺).
Example 54: N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-(3-(2-(dimethylamino)ethyl)ureido)benzenesulfonamide. ¹H NMR (400 MHz, DMSO-d₆) δ 8.91 (br s, 1 H), 8.81 (s, 1 H), 8.08 (s, 1 H), 7.60 (s, 1 H), 7.38 (m, 9 H), 6.28 (m, 1 H), 6.15(s, I H), 3.78 (s, 6 H), 3.40 (m, 2 H), 3.08 (m, 2 H), 2.74 (s, 6 H); MS (EI) m/z for C₂₇H₃₁N₇O₅S: 566 (MH⁺).
Example 55: 1-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)cyclopentanecarboxamide. ¹H NMR (400 MHz, DMSO-d₆) δ 12.40 (br s, 1 H), 10.58 (s, I H), 8.46 (m, 4 H), 7.80 (m, 3 H), 7.59 (m, 2 H), 7.34 (m, 4 H), 6.25 (m, 1 H), 3.76 (s, 6 H), 2.35 (m, 2 H), 1.90 (m, 8 H); MS (EI) m/z for C₂₈H₃₀N₆O₅S: 563 (MH⁺).
Example 56: 1-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)cyclopropanecarboxamide. ¹H NMR (400 MHz, DMSO-d₆) δ 9.54 (br s, 1 H), 8.84 (s, 1 H), 8.29 (s, 1 H), 7.75 (m, 2 H), 7.39 (m, 6 H), 7.17 (m, 2 H), 6.16 (m, 1 H), 3.78 (s, 6 H), 1.52 (m, 2 H), 1.17 (m, 2 H); MS (EI) m/z for C₂₆H₂₆N₆O₅S: 535 (MH⁺).
Example 57: 2-(dimethylamino)ethyl 3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenylcarbamate. ¹H NMR (400 MHz, DMSO-d₆) δ 9.78 (br s, I H), 8.79 (s, I H), 8.19 (s, 1 H), 7.66 (d, 1 H), 7.31 (m, 9 H), 6.14 (m, 1 H), 4.17 (t, 2 H), 3.78 (s, 6 H), 2.54 (t, 2 H), 2.21 (s, 6 H): MS (EI) m/z for C₂₇H₃₀N₆O₆S: 567 (MH⁺).
Example 58: 4-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)tetrahydro-2H-pyran-4-carboxamide. ¹H NMR (400 MHz, DMSO-d₆) δ 12.2 (br s, 1 H), 10.6 (s, 1 H), 8.74 (m, 5 H), 7.93 (m, 2 H), 7.47 (m, 6 H), 6.24 (m, 1 H), 3.77 (m, 10 H), 2.45 (m, 2 H), 1.81 (m, 2 H); MS (EI) m/z for C₂₈H₃₀N₆O₆S: 579 (MH⁺).
Example 59: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-N3-(2-(dimethylamino)ethyl)benzene-1,3-disulfonamide. ¹H NMR (400 MHz, DMSO-d₆) δ 9.35 (m, 2 H), 8.92 (m, 1 H), 8.64 (s, 1 H), 8.30 (m, 1 H), 8.11 (s, 1 H), 7.86 (m, 1 H), 7.68 (m, 1 H), 7.49 (s, 1 H), 7.42 (m, 2 H), 7.21 (m, 2 H), 6.61 (m, 1 H), 3.82 (s, 3 H), 3.05 (m, 4 H), 2.74 (s, 6 H); MS (EI) m/z for C₂₅H₂₇ClN₆O₅S₂: 591 (MH⁺).
Example 60: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-N3-(3-(dimethylamino)propyl)benzene-1,3-disulfonamide. ¹H NMR (400 MHz, DMSO-d₆) δ 9.38 (m, 2 H), 8.90 (m, 1 H), 8.60 (s, 1 H), 8.32 (m, I H), 8.12 (s, 1 H), 7.88 (m, 1 H), 7.72 (m, 1 H), 7.59 (s, I H), 7.40 (m, 2 H), 7.20 (m, 2 H), 6.67 (m, I H), 3.82 (s, 3 H), 2.97 (m, 2 H), 2.78 (m, 2 H), 2.71 (s, 6 H), 1.70 (m, 2 H); MS (EI) m/z for C₂₆H₂₉ClN₆O₅S₂: 605 (MH⁺).
Example 61: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-4-methylphenyl)-2-(methylamino)acetamide. MS (EI) m/z for C₂₅H₂₅ ClN₆O₄S: 541.0 (MH⁺).
Example 62: (S)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-4-methylphenyl)propanamide. MS (EI) m/z for C₂₅H₂₅ ClN₆O₄S: 541.2 (MH⁺).
Example 63: (R)-2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-4-methylphenyl)propanamide. MS (EI) m/z for C₂₅H₂₅ ClN₆O₄S: 541.0 (MH⁺).
Example 64: (S)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)propanamide. MS (EI) m/z for C₂₆H₂₈ N₆O₅S: 537.1 (MH⁺).
Example 65: (R)-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)propanamide. MS (EI) m/z for C₂₅H₂₅ ClN₆O₄S: 541.1(MH⁺).
Example 66: (R)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)propanamide. MS (EI) m/z for C₂₆H₂₈N₆O₃S: 537.3 (MH⁺).
Example 67: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)piperidine-2-carboxamide. MS (EI) m/z for C₂₈H₃₀N₆O₅S: 563.1 (MH⁺).
Example 68: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-(dimethylamino)ethylamino)acetamide. MS (EI) m/z for C₂₈H₃₃N₇O₅S: 580.1 (MH⁺).
Example 69: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sultamoyl)phenyl)-2-(4-(methylamino)piperidin-1-yl)acetamide. MS (EI) m/z for C₃₀H₃₅N₇O₆S: 606.1 (MH⁺).
Example 70: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-(dimethylamino)piperidin-1-yl)acetamide. MS (EI) m/z for C₃₁H₃₇N₇O₅S: 620.1 (MH⁺).
Example 71: N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide. ¹H NMR (400 MHz, DMSO) δ 12.4 (br s, 1H), 10.9 (s, 1H), 9.8 (s, 1H), 8.9 (s, 1H), 8.3 (br s, 1H), 7.9 (d, 2H), 7.8 (d, 1H), 7.6 (t, 2H), 7.4 (q, 2H), 7.3 (s, 1H), 6.25 (s, 1H), 4.15 (s, 2H), 3.8 (s, 6H), 2.9 (s, 6H). MS (EI) m/z for C₂₆H₂₈N₆O₅S 2.0 x C₂H₁O₂F₃: 537.1 (MH⁺).
Example 72: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(ethylamino)acetamide. ¹H NMR (400 MHz, DMSO) δ 10.8 (s, 1H), 9.20 (s, 1H), 8.84 (br s, 2H), 8.64 (br s, 1H), 8.30 (s, 1H), 7.9-8.0 (br s, 1H), 7.80 (t, 2H), 7.55-7.68 (m, 2H), 7.4 (d, 3H), 6.70 (m, 1H), 3.97 (br s, 2H), 3.83 (s, 3H), 3.04 (br s, 2H), 1.3 (t, 3H). MS (EI) m/z for C₂₅H₂₅ClN₆O₄S 2.0 x C₂H₁O₂F₃: 541.3, 543.2 (MH⁺).
Example 73: 2-(azetidin-1-yl)-N-(3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. ¹H NMR (400 MHz, DMSO) δ 10.8 (s, 1H), 10.2 (s, 1H), 9.2 (s, 1H), 8.7 (s, 1H), 8.3 (s, 1H), 7.9-8.0 (br s, 1H), 7.80 (d, 1H), 7.72 (d, 1H), 7.65 (br s, 1H), 7.56 (t, 1H), 7.40 (d, 3H), 6.70 (m, 1H), 4.28 (s, 2H), 4.15 (m, 4H), 3.82 (s, 3H), 2.32 (br s, 1H). MS (EI) m/z for C₂₆H₂₅ClN₆O₄S 2.0 x C₂H₁O₂F₃: 553.3, 555.2 (MH⁺).
Example 74: N-(3-(N-(3-(2-bromo-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)acetamide. The title compound was prepared according to the Examples above, ¹H NMR (400 MHz, DMSO) δ 10.6 (s, 1H), 9.5 (s, I H), 8.95 (d, 1H), 8.18 (t, 1H), 7.78 (m, 1H), 7.70 (m, 1H), 7.54 (d, 1H), 7.46 (m, 1H), 7.38 (t, 1H), 7.32 (d, 1H), 7.12-7.22 (m, 2H), 6.56 (m, 1H), 3.90 (s, 2H), 3.82 (s, 3H), 2.62 (s, 3H). MS (EI) m/z for C₂₄H₂₃BrN₆O₄S: 572.77, 570.90 (MH⁺).
Example 75: 2-(dimethylamino)-N-(3-(N-(3-(6-methoxy-quinolin-8-ylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. The title compound was prepared according to the Examples above. ¹H NMR (400 MHz, DMSO) δ 10.9 (s, 1H), 10.6 (s, 1H), 9.13 (s, 1H), 8.80 (d, 1H), 8.26-8.30 (m, 2H), 7.85 (d, 1H), 7.70 (d, 1H), 7.60 (q, 1H), 7.54 (m, 1H), 7.44 (t, 2H), 7.20 (t, 2H), 6.80 (d, 1H), 4.00 (s, 2H), 3.94 (s, 3H), 2.78 (s, 6H). MS (EI) m/z for C₂₈H₂₇N₇O₄S: 558.3 (MH⁺).
Example 76: N-(3-(N-(3-(2-bromo-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide. ¹H NMR (400 MHz, DMSO) δ 10.6 (s, 1H), 9.4 (s, 1H), 8.9 (s, 1H), 8.25 (s, 1H), 7.78 (d, 1H), 7.70 (d, 1H), 7.54 (d, 1H), 7.48 (d, 1H), 7.40 (t, 2H), 6.56 (d, 1H), 4.02 (s, 2H), 3.82 (s, 3H), 2.80 (s, 6H). MS (EI) m/z for C₂₅H₂₅BrN₆O₄S: 586.79, 584.91 (MH⁺).
Example 77: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-fluoroethylamino)acetamide. ¹H NMR (400 MHz, DMSO) δ 10.6 (s, 1H), 9.4 (s, 1H), 8.9 (d, 1H), 8.20 (s, 1H), 7.78 (d, 1H), 7.70 (d, 1H), 7.48 (m, 1H), 7.36-7.44 (m, 3H), 7.20 (q, 3H), 6.6 (m, 1H), 4.78 (t, 1H), 4.66 (t, 1H), 3.94 (s, 2H), 3.82 (s, 3H), 3.4 (t, 1H), 3.3 (t, 1H). MS (EI) m/z for C₂₅H₂₄ClFN₆O₄S: 559.2, 561.2 (MH⁺).
Example 78: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)formamide. ¹H NMR (400 MHz, DMSO) δ 12.4 (br s, 1H), 10.5 (s, 1H), 8.90 (s, 1H), 8.3 (s, 1H), 7.9 (br s, 1H), 7.85 (d, 1H), 7.75 (d, 1H), 7.5-7.6 (m, 2H), 7.3-7.4 (m, 4H), 6.2 (s, 1H), 3.8 (s, 3H). MS (EI) m/z for C₂₃H₂₁N₅O₅S: 480.1 (MH⁺).
Example 79: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-(dimethylamino)azetidin-1-yl)acetamide. ¹H NMR (400 MHz, DMSO) δ 10.2 (br s, 1H), 9.5 (s, 1H), 8.95 (d, 1H), 8.2 (s, 1H), 7.75 (d, 1H), 7.65 (d, 1H), 7.45 (d, 1H), 7.40 (d, 1H), 7.30-7.35 (t, 1H), 7.1-7.2 (q, 2H), 6.60 (m, 1H), 3.82 (s, 3H). MS (EI) m/z for C₂₈H₃₀ClN₇O₄S: 480.1 (MH⁺).
Example 80: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(pyrrolidin-1-yl)acetamide. MS (EI) m/z for C₂₈H₃₀N₆O₅S: 563.18 (MH⁺).
Example 81: N-(3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(ethyl(methyl)amino)acetamide. ¹H NMR (400 MHz, DMSO) δ 12.0 (s, 1H), 10.6 (s, 1H), 9.65 (s, 1H), 9.5 (s, 1H), 8.95 (s, 1H), 8.25 (s, 1H), 7.8 (d, 1H), 7.70 (d, 1H), 7.45-7.50 (d, 1H), 7.3-7.4 (m, 3H), 7.2 (t, 2H), 6.60 (d, 1H), 4.02 (br s, 2H), 3.82 (s, 3H), 3.14 (br s, 2H), 2.80 (s, 3H) 1.2 (t, 3H). MS (EI) m/z for C₂₆H₂₇ClN₆O₄S: 555.2, 557.3 (MH⁺).
Example 82: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-(piperidin-1-yl)azetidin-1-yl)acetamide. MS (EI) m/z for C₃₁H₃₄ClN₇O₄S 2.0 x C₂H₁O₂F₃: 636.3, 638.3 (MH⁺).
Example 83: N-(3-(N-(3-(3-fluoro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)acetamide. MS (EI) m/z for C₂₄H₂₃FN₆O₄S: 511.04 (MH⁺).
Example 84: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-methylpiperidine-4-carboxamide. MS (EI) m/z for C₂₉H₃₂N₆O₅S 1.0 x C₂H₄O₂: 577.2 (MH⁺).
Example 85: N-(3-(N-(3-(3-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)acetamide. ¹H NMR (400 MHz, DMSO) δ 10.6 (s, 1H), 8.82 (s, 1H), 8.22 (t, 1H), 7.86 (t, 1H), 7.76 (m, 1H), 7.66 (m, 1H), 7.46 (m, 1H), 7.41 (m, 1H), 7.38 (t, 1H), 7.28 (m 1H), 7.24 (t, 1H), 7.12 (m, 2H), 6.56 (d, 1H), 3.88 (s, 2H), 3.80 (s, 3H), 2.60 (s, 3H). MS (EI) m/z for C₂₄H₂₄N₆O₄S: 492.99 (MH⁺).
Example 86: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2,2,2-trifluoroethylamino)acetamide. ¹H NMR (400 MHz, DMSO) δ 10.4 (s, 1H), 9.2 (s, 1H), 8.65 (s, 1H), 8.4 (s, 1H), 8.00 (m, 1H), 7.80 (d, 1H), 7.75 (d, 1H), 7.65 (q, 1H), 7.55 (t, 1H), 7.40-7.5 (m, 3H), 6.7 (m, 1H), 3.82 (s, 3H), 3.62 (br s, 2H), 3.55 (br d, 2H). MS (EI) m/z for C₂₅H₂₂ClF₃N₆O₄S 1.0 x C₂H₁O₂F₃: 595.0, 597.0 (MH⁺).
Example 87: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-(piperidin-1-yl)propanamide. MS (EI) m/z for C₃₀H₃₄N₆O₅S: 591.2 (MH⁺).
Example 88: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-(dimethylamino)butanamide. MS (EI) m/z for C₂₈H₃₂N₆O₅S 1.0 x C₂H₄O₂: 565.2 (MH⁺).
Example 89: 2-(dimethylamino)-N-(3-(N-(3-(3-fluoro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. ¹H NMR (400 MHz, DMSO) δ 10.9 (s, 1H), 9.8 (br s, 1H), 9.1 (s, 1H), 8.34 (s, 1H), 7.90 (d, 1H), 7.76 (d, 1H), 7.52-7.68 (m, 4H), 7.40 (m, 2H), 6.54 (m, 1H), 4.16 (s, 2H), 3.82 (s, 3H), 2.86 (s, 6H). MS (EI) m/z for C₂₅H₂₅FN₆O₄S: 525.05 (MH⁺).
Example 90: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(piperidin-1-yl)acetamide. MS (EI) m/z for C₂₉H₃₂N₆O₅S: 577.37 (MH⁺).
Example 91: 2-(dimethylamino)-N-(3-(N-(3-(3-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. ¹H NMR (400 MHz, DMSO) δ 10.5 (s, 1H), 8.8 (s, 1H), 8.25 (s, 1H), 7.83 (t, 1H), 7.76 (d, 1H), 7.64 (d, 1H), 7.3-7.48 (m, 4H), 7.22 (t, 1H), 7.12 (t, 2H), 6.56 (m, 1H), 3.96 (s, 2H), 3.78 (s, 3H), 2.76 (s, 6H). MS (EI) m/z for C₂₅H₂₆N₆O₄S: 507.1 (MH⁺).
Example 92: N-(3-(N-(3-(2-chloro-5-hydroxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide. ¹H NMR (400 MHz, DMSO) δ 10.8 (s, 1H), 9.9 (s, 1H), 9.8 (s, 1H), 9.1 (s, 1H), 8.55 (s, 1H), 8.34 (s, 1H), 7.9-8.0 (br s, 1H), 7.82 (d, 1H), 7.76 (d, 1H), 7.52-7.66 (m, 2H), 7.42 (t, 1H), 7.26 (d, 1H), 6.50 (m, 1H), 4.16 (s, 2H), 2.86 (s, 6H). MS (EI) m/z for C₂₄H₂₃ClN₆O₄S: 527.1, 529.0 (MH⁺).
Example 93: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-morpholinoacetamide. MS (EI) m/z for C₂₈H₃₀N₆O₆S: 579.1 (MH⁺).
Example 94: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z for C₂₄H₂₃N₅O₅S: 494.0 (MH⁺). Example 97: 2-amino-N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-4-methylphenyl)-2-methylpropanamide. MS (EI) m/z for C₂₆H₂₇ClN₆O₄S: 556.12 (MH⁺).
Example 98: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide. MS (EI) m/z for C₂₅H₂₅ClN₆O₄S: 542.05 (MH⁺).
Example 99: 2-amino-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z for C₂₄H₂₄N₆O₅S: 509.59 (MH⁺).

Example 100

3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)benzoic acid

[0306] 

[0307] To a solution of N-(3-{[2-chloro-5-(methoxy)-phenyl]amino}quinoxalin-2-yl)-3-cyanobenzenesulfonamide (6.02 g, 12.95 mmol), prepared using procedures similar to those in Example 115 or Example 423, in methanol (20 mL) and 1,4-dioxane (20 mL) was added 6.0 N aqueous sodium hydroxide (40 mL) at room temperature. The solution was stirred at 90 °C for 3.5 h. The reaction was cooled to room temperature and neutralized slowly by adding 2.0 N hydrochloric acid until the pH of the solution became in the 2-3 range at 0° C. The solution was diluted with ethyl acetate (300 mL). The organic layer was washed with saturated aqueous sodium chloride (50 mL) and dried over magnesium sulfate. Filtration and concentration at reduced pressure afforded 3-{[(3-{[2-chloro-5-(methoxy)-phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}benzoic acid (5.921 g, 94%). MS (EI) m/z for C₂₂H₁₇ ClN₄O₅S: 485.0 (MH⁺).

[0308] The following compounds were preapred using procedures ismilar to those used in Example 100.
Example 101: Proceeding as above, 3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)benzoic acid was prepared. MS (EI) m/z for C₂₃H₂₀N₄O₆S: 481.0 (MH⁺).
Example 102: 3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-methyl-1-(piperidin-1-yl)propan-2-yl)benzamide. MS (EI) m/z for C₃₁H₃₅ClN₆O₄S: 623.06 (MH⁺).
Example 103: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-methyl-1-oxo-1-(piperidin-1-yl)propan-2-yl)benzamide. MS (EI) m/z for C₃₁H₃₃ClN₆O₅S: 637.65 (MH⁺).

Example 104

3-{[(3-{[2-chloro-5-(methoxy)phenyliamino}quinoxalin-2-yl)amino]sulfonyl}-N-[2-(dimethylamino)ethyl]benzamide

[0309] 

[0310] To a solution of 3-{[(3-{[2-chloro-5-(methoxy)phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}benzoic acid (0.20 g, 0.42 mmol), prepared using procedures similar to Example 100, in dimethylformamide (4 mL) were added 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 0.32 g, 0.83 mmol) and N-ethyldiisopropylamine (DIEA, 0.13 g, 1.04 mmol) at room temperature. The reaction was stirred for 15 min before N,N-dimethylethane-1,2-diamine (73 mg, 0.83 mmol) was added. The reaction mixture was allowed to stir overnight. The reaction was diluted with ethyl acetate (200 mL) and washed with water (50 mL), saturated aqueous sodium bicarbonate (40 mL), 1.0 N aqueous hydrochloric acid (30 mL), and saturated aqueous sodium chloride (25 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated at reduced pressure to afford 3-{[(3-{[2-chloro-5-(methoxy)phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}-N-[2-(dimethylamino)ethyl]benzamide (0.20 g, 87%) as yellow solid. MS (EI) m/z for C₂₆H₂₇ ClN₆O₄S: 555.1 (MH⁺).

[0311] The following compounds were prepared using procedures similar to those in Example 104.
Example 105: 5-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(dimethylamino)ethyl)-2-methoxybenzamide. ¹H NMR (400 MHz, DMSO-d₆) δ 9.45 (s, 1H), 8.95 (d, 1H), 8.57 (d, 1H), 8.28 (t, 1H), 8.14 (dd, 1H), 7.46 (dd, 1H), 7.39 (m, 2H), 7.17 (m, 4H), 6.60 (dd, 1H), 3.89 (s, 3H), 3.82 (s, 3H), 3.38 (m, 2H), 2.43 (m, 2H), 2.21 (s, 6H). MS (EI) m/z for C₂₇H₂₉ClN₆O₅S: 585.3 (MH⁺). Example 106: 5-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(dimethylamino)ethyl)-2-fluorobenzamide. ¹H NMR (400 MHz, DMSO-d₆) δ 9.40 (br s, 1H), 9.16 (s, 1H), 8.73 (m, 1H), 8.67 (d, 1H), 8.36 (dd, 1H), 8.26 (m, 1H), 7.94 (br s, 1H), 7.66 (m, 1H), 7.59 (t, 1H), 7.43 (m, 3H), 6.71 (dd, 1H), 3.83 (s, 3H), 3.62 (m, 2H), 3.27 (m, 2H), 2.85 (d, 6H). MS (EI) m/z for C₂₆H₂₆ClFN₆O₄S: 573.1 (MH⁺).
Example 107: 3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(dimethylamino)ethyl)benzamide. MS (EI) m/z for C₂₇H₃₀N₆O₅S: 551.1 (MH⁺).
Example 108: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(dimethylamino)ethyl)-N-methylbenzamide. MS (EI) m/z for C₂₇H₂₉ClN₆O₄S: 569.1 (MH⁺).
Example 109: 3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(dimethylamino)ethyl)-N-methylbenzamide. MS (EI) m/z for C₂₈H₃₂N₆O₅S: 565.1 (MH⁺).
Example 110: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)benzamide. MS (EI) m/z for C₂₂H₁₈ ClN₅O₄S: 484.0 (MH⁺).
Example 111: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-morpholinoethyl)benzamide. MS (EI) m/z for C₂₈H₂₉ ClN₆O₅S: 597.0 (MH⁺).
Example 112: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-methylbenzamide. MS (EI) m/z for C₂₃H₂₀ ClN₅O₄S: 498.0 (MH⁺).
Example 113: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-morpholinobenzamide. MS (EI) m/z for C₂₆H₂₅ ClN₆O₅S: 569.0 (MH⁺).

Example 114

N-(3-{[2-chloro-5-(methoxy)phenyl]amino}quinoxalin-2-yl)-3-{5-[(dimethylamino)methyl]-1,3,4-oxadiazol-2-yl}benzenesulfonamide

[0312] 

[0313] To a solution of 3-{[(3-{[2-chloro-5-(methoxy)phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}benzoic acid (0.25 g, 0.52 mmol), prepared as described above in Example 100, in dimethylformamide (2.6 mL) were added 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 0.25 g, 0.67 mmol) and N-ethyldiisopropylamine (DIEA, 0.11 g, 0.88 mmol) at room temperature. The reaction was stirred for 15 min before 2-(dimethylamino)acetohydrazide (78 mg, 0.67 mmol) was added. The reaction mixture was allowed to stir overnight. The reaction was diluted with ethyl acetate (200 mL) and washed with water (30 mL), saturated aqueous sodium bicarbonate (30 mL), 1.0 N aqueous hydrochloric acid (20 mL), and saturated aqueous sodium chloride (25 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated at reduced pressure to afford 180 mg of a coupled intermediate which was then heated in phosphorus oxychloride (5 mL) at 100 0C for 4h. The reaction was cooled to room temperature and treated with ice water (50 mL) and extracted with dichloromethane (3 X 50 mL). The organic layer was dried over magnesium sulfate, filtered and concentrated at reduced pressure to afford a crude product which was subjected to reverse phase HPLC to afford N-(3-{[2-chloro-5-(methoxy)-phenyl]amino} quinoxalin-2-yl)-3- {5-[(dimethylamino)methyl]-1,3,4-oxadiazol-2-yl}-benzenesulfonamide (16 mg, 5 %) as yellow solid. MS (EI) m/z for C₂₆H₂₄ ClN₇O₄S: 566.0 (MH⁺).

Example 115

N-(3-(3-methoxy-5-nitro-phenylamino)-quinoxalin-2-yl)-3-nitrobenzenesulfonamide

[0314] 

[0315] N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide. 2,3-Dichloroquinoxaline (26.1 g, 131.1 mmol), m-Nitrobenzene sulfonamide (26.5 g, 131.1 mmol) and potassium carbonate (18.1 g, 131.1) were dissolved in anhydrous DMSO (500 mL). The reaction was heated to 150 °C for 2 h. The reaction mixture was poured into water (400 mL), followed by addition of 2M HCl (60 mL). The product was extracted with EtOAc (3 x 500 mL). The organic layers were combined and washed water (2 x 500 mL) and brine (2 x 500 mL). The product was then dried with sodium sulfate to give N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide. MS (EI) m/z for C₁₄H₉ClN₄O₄S: 364.94, 366.97 (MH⁺)

[0316] N-(3-(3-methoxy-5-nitrophenylamino)quinoxalin-2-yl)-3-nitro-benzenesulfonamide. N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide (700 mg, 1.92 mmol), 3-methoxy-5-nitroaniline (645 mg, 3.84 mmol) and p-xylene (7 mL) were combined and heated to 140°C, then stirred for 16 hours at 130 °C. The reaction was allowed to cool, placed in a sep. funnel, diluted with DCM, and washed with 2M HCl and brine and concentrated in vacuo. The resulting solid was washed with Et₂O to give N-(3-(3-methoxy-5-nitro-phenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide (400 mg, 42%). MS (EI) m/z for C₂₁H₁₆N₆O₇S: 496.94 (MH⁺).

[0317] The following compounds were prepared using procedures similar to those in Example 115.
Example 116: N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)-3-cyanobenzenesulfonamide. MS (EI) m/z for C₂₂H₁₆ClN₅O₃S: 465.9 (MH⁺). Example 117: 3-cyano-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₃H₁₉N₅O₄S: 462.3 (MH⁺).
Example 118: N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-fluorobenzenesulfonamide. MS (EI) m/z for C₂₂H₁₉FN₄O₄S: 456.0 (MH⁺). Example 119: 3-bromo-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₂H₁₉BrN₄O₄S: 516.9 (MH⁺).
Example 120: 3-bromo-N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₂H₁₉BrN₄O₄S: 516.9 (MH⁺).
Example 121: N-(3-(3-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₁H₁₈N₄O₃S: 407.0 (MH⁺).
Example 122: N-(3-(4-fluoro-3-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₁H₁₇FN₄O₃S: 425.0 (MH⁺).
Example 123: N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide. MS (EI) m/z for C₂₃H₂₂N₄O₅S: 467.0 (MH⁺).
Example 124: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-methoxybenzenesulfonamide. MS (EI) m/z for C₂₃H₂₂N₄O₅S: 467.0 (MH⁺).
Example 125: N-(3-(4-chloro-3-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₁H₁₇ClN₄O₃S: 440.9 (MH⁺).
Example 126: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)thiophene-2-sulfonamide. MS (EI) m/z for C₂₀H₁₈N₄O₄S₂: 443.0 (MH⁺).
Example 127: N-(3-(6-methoxyquinolin-8-ylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide. MS (EI) m/z for C₂₄H₁₈N₆O₅S: 502.95 (MH⁺).
Example 128: 3-nitro-N-(3-(pyridin-4-ylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₁₉H₁₄N₆O₄S: 423.2 (MH⁺).
Example 129: N-(3-(2-chloropyridin-4-ylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide. MS (EI) m/z for C₁₉H₁₃ClN₆O₄S: 456.93, 458.90 (MH⁺).
Example 130: N-(3-(4,6-dimethoxypyrimidin-2-ylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide. MS (EI) m/z for C₂₀H₁₇N₇O₆S: 484.03 (MH⁺).
Example 131: N-(3-(4-hydroxy-6-methoxypyrimidin-2-ylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide. MS (EI) m/z for C₁₉H₁₅N₇O₆S: 469.97 (MH⁺).
Example 132: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2-fluorobenzenesulfonamide. MS (EI) m/z for C₂₂H₁₉FN₄O₄S: 455.3 (MH⁺).
Example 133: N-(3-(2-bromo-5-methoxy-phenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide. MS (EI) m/z for C₂₁H₁₆BrN₅O₅S: 531.82, 532.84 (MH⁺).
Example 134: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-methylbenzenesulfonamide. MS (EI) m/z for C₂₃H₂₂N₄O₄S: 451.0 (MH⁺).
Example 136: N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-methylbenzenesulfonamide. MS (EI) m/z for C₂₃H₂₂N₄O₄S: 451.0 (MH⁺).
Example 137: N-(3-(3-fluoro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide. MS (EI) m/z for C₂₁H₁₆FN₅O₅S: 470.0 (MH⁺).
Example 138: 4-bromo-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₂H₁₉BrN₄O₄S: 516.9, 514.9 (MH⁺).
Example 139: N-(3-(3-methoxyphenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide. MS (EI) m/z for C₂₁H₁₇N₅O₅S: 451.93 (MH⁺).
Example 140: N-(3-(2-chloro-5-hydroxy-phenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide. MS (EI) m/z for C₂₀H₁₄ClN₅O₅S: 472.15, 474.13 (MH⁺).
Example 141: 3-acetyl-N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₃H₁₉ClN₄O₄S: 483.08 (MH⁺).
Example 142: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₂H₂₀N₄O₄S: 437.49 (MH⁺).
Example 143: N-(3-(5-methoxy-2-methyl-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₂H₂₀N₄O₃S: 421.46 (MH⁺).
Example 144: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₁H₁₇ClN₄O₃S: 440.59 (MH⁺).
Example 145: N-(3-(2,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₂H₂₀N₄O₄S: 437.53 (MH⁺).
Example 146: 4-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₂H₁₉ClN₄O₄S: 470.54 (MH⁺). Example 147: N-(3-(5-methoxy-2-methyl-phenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide. MS (EI) m/z for C₂₂H₁₉N₅O₅S: 466.32 (MH⁺).
Example 148: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide. MS (EI) m/z for C₂₁H₁₆ClN₅O₅S: 485.86 (MH⁺).
Example 149: N-(3-(4-chloro-2,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₂H₁₉ClN₄O₄S: 470.99 (MH⁺).

Example 150

N-(3-{[3,5-bis(methoxy)phenyl]amino}quinoxalin-2-yl)-3-(2H-tetrazol-5-yl)benzenesulfonamide

[0318] 

[0319] To a stirred solution of 3-cyano-N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide (0.20 g, 0.44 mmol), prepared using procedures similar to those described in Example 115, in dimethylformamide (1.2 mL) at 50 °C were added sodium azide (0.11 g, 1.76 mmol) and ammonium chloride (94 mg, 1.76 mmol). The crude mixture was heated at 100 °C overnight. The reaction was cooled to room temperature treated with ice water (20 mL) followed by concentrated hydrochloric acid (10 mL). The solid obtained was filtered under reduced pressure and washed with hexane (20 mL), diethyl ether (20 mL), and ethyl acetate (5 mL) to afford N-(3-{[3,5-bis(methoxy)phenyl]amino}quinoxalin-2-yl)-3-(2H-tetrazol-5-yl)benzenesulfonamide (55 mg, 25%) as light yellow solid. MS (EI) m/z for C₂₃H₂₀N₈O₄S: 505.0 (MH⁺).

Example 151

N-(3-(2,6-dichloropyridin-4-ylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide.

[0320] A mixture of N-(3-chloroquinoxalin-2-yl)-3-nitrobenzenesulfonamide (1 g), 2,6-dichloropyridin-4-amine (760 mg) and p-xylene (10 mL) was heated at 135 °C with stirring overnight. Upon cooling to room temperature, the mixture was dissolved in dichloromethane, washed with 2 N HCl (2 x) and brine, concentrated in vacuo to give a crude product of N-{3-[(2,6-dichloropyridin-4-yl)amino]quinoxalin-2-yl}-3-nitrobenzenesulfonamide. A small portion of this crude product was purified by HPLC to give N-{3-[(2,6-dichloropyridin-4-yl)amino]quinoxalin-2-yl}-3-nitro-benzenesulfonamide. ¹H NMR (400 MHz, DMSO) δ 9.71 (s, 1H), 8.90 (s, 1H), 8.50 (d, 2H), 8.8.41 (d, 1H), 8.30 (s, 2H), 7.88-7.78 (m, 27.65 (d, 1H), 7.47-7.37 (m, 2H); MS (EI) m/z for C₁₉H₁₂Cl₂N₆O₄S: 491.1, 493.1 (MH⁺).

Example 152

N-(3-(2-chloro-6-methoxypyridin-4-ylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide

[0321] To a crude product of N-{3-[(2,6-dichloropyridin-4-yl)amino]quinoxalin-2-yl}-3-nitrobenzenesulfonamide (1.24 g) prepared using procedures similar to those for Example 151, was added anhydrous DMSO (10 mL), followed by sodium methoxide (273 mg). The resulting mixture was heated at 100 °C for 3 days. The mixture was diluted with EtOAc and water, and the pH was adjusted to about 4 by adding acetic acid. The product was extracted with EtOAc (3 x). The combined extracts were washed with brine to give the crude product. A portion of the crude product was purified by prep HPLC to give N-(3-{[2-chloro-6-(methyloxy)pyridin-4-yl]amino}quinoxalin-2-yl)-3-nitrobenzenesulfonamide. 1H NMR (400 MHz, DMSO) δ 9.44 (s, 1H), 8.90 (s, 1H), 8.50 (d, 1H), 8.42 (d, 1H), 7.88-7.84 (m, 2H), 7.77 (s, 1H), 7.74 (s, 1H), 7.64 (d, 1H), 7.45-7.38 (m, 2H), 3.82 (s, 3H); MS (EI) m/z for C₂₀H₁₅ClN₆O₅S: 496.94 (MH⁺).

Example 153

2-(dimethylamino)-N-(3-(N-(3-(3-(2-(dimethylamino)acetamido)-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide

[0322] 

[0323] 3-amino-N-(3-(3-amino-5-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide. N-(3-(3-Methoxy-5-nitrophenylamino)quinoxalin-2-yl)-3-nitrobenzenesulfonamide (400 mg, 0.81 mmol), prepared as described above in Example 115, was dissolved in 1:1 I THF:EtOH (4 mL), to which was added formic acid (938 µl, 2.42 mmol) and potassium formate (203 mg, 2.42 mmol). The system was flushed with nitrogen, and then 10%wt Pd/C (50 mg) was added. The reaction was then heated to 60°C. Once the reaction was determined complete by LC-MS, it was allowed to cool, and DMF was added for solubility. The solution was then filtered through a nylon frit to remove the catalyst. The filtrate was diluted water and the pH adjusted to 7 and extracted with DCM (2x) and EtOAc (2x). All organic layers were combined and evaporated to dryness to give 3-amino-N-(3-(3-amino-5-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide (330 mg, 93%). MS (EI) m/z for C₂₁H₂₀N₆O₃S: 437.06 (MH⁺)

[0324] 2-(dimethylamino)-N-(3-(N-(3-(3-(2-(dimethylamino)-acetamido)-5-methoxyphenylamino)quinoxalin-2-yl)-sulfamoyl)phenyl)acetamide. 3-Amino-N-(3-(3-amino-5-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide (330 mg, 0.76 mmol), DMF (4 mL), N,N,-Dimethylglycine (312 mg, 3.02 mmol), HATU (1.15 g, 3.02 mmol), and 1.29(mL) (7.56 mmol) DIEA (1.29 mL, 7,56 mmol) were combined and heated to 90°C, followed by heating at 50°C for over 16 hours. The reaction was allowed to cool, placed into a sep. funnel diluted with water and aqueous LiCl and extracted with EtOAc. The final compound was then purified by prep. HPLC to give 2-(dimethylamino)-N-(3-(N-(3-(3-(2-(dimethylamino)acetamido)-5-methoxy-phenylamino)-quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. ¹H NMR (400 MHz, CD₃OD) δ 8.45 (t, 1H), 7.93 (t, 1H), 7.85-7.88 (m, 1H), 7.70-7.74 (m, 1H), 7.65-7.68 (m, 1H), 7.58-7.62 (m, 1H), 7.58 (t, 1H), 7.34-7.42 (m, 3H), 7.0 (t, 1H), 4.05 (d, 2H), 3.8 (s, 3H), 2.9-3.0 (d, 12H). MS (EI) m/z for C₂₀H₃₄N₈O₅S: 607.2 (MH⁺).

[0325] The following title compounds were prepared using procedures similar to those in Example 153.
Example 154: N-(3-(2,5-dimethoxyphenylamino)-7-methylquinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z for C₂₃H₂₂N₄O₄S: 451.0 (MH⁺).

Example 155a and Example 155b

N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-(methylamino)benzenesulfonamide and N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-(dimethylamino)benzenesulfonamide.

[0326] 

[0327] To a solution of 3-amino-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide (414 mg) in DMF (4.5 mL) was added iodomethane (114 µL). The reaction mixture was heated at 35-50 °C until the formation of both mono-methylated and di-methylated products was detected by LC/MS. The mixture was diluted with EtOAc, washed with water, 10% LiCl (2 x) and brine. After removal of solvent in vacuo, the crude mixture was purified by flash silica column chromatography eluting with 15% EtOAc in hexanes, affording the mono-methylated and di-methylated products. Product A: N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-(methylamino)-benzenesulfonamide (35 mg). ¹H NMR (400 MHz, DMSO) δ 12.2 (s, 1H), 8.93 (s, 1H), 7.85 (d, 1H), 7.58 (d, 1H), 7.40-7.20 (m, 7H), 6.76 (m, 1H), 6.24 (m, 1H), 6.16 (br s, 1H), 3.77 (s, 6H), 2.71 (s, 3H). MS (EI) for C₂₃H₂₃N₅O₄S: 466.05 (MH+). Product B: N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)-3-(dimethylamino)benzenesulfonamide (33 mg). ¹H NMR (400 MHz, DMSO) δ 1220 (s, 1H), 8.98 (s, 1H), 7.98 (d, 1H), 7.56 (d, 1H), 7.42-7.32 (m, 7H), 6.74 (m, 1H), 6.24 (m, 1H), 3.77 (s, 6H), 2.97 (s, 6H). MS (EI) for C₂₄H₂₅N₅O₄S: 480.04 (MH+).

Example 156

N-(3-{[(2-{[3,5-bis(methoxy)phenyl]amino}pyrido[2,3-b]pyrazin-3-yl)amino]sulfonyl}phenyl)-N-2-[2-(dimethylamino)ethyl]-N-2-methylglycinamide

[0328] 

[0329] To a THF suspension (1.3 mL) of 3-amino-N-(3-{[3,5-(dimethoxy)-phenyl]amino}-quinoxalin-2-yl)benzenesulfonamide (126 mg, 0.28 mmol), prepared using procedures similar to those described for Example 15, was added 0.143 mL of 2M aqeuos Na₂CO₃. To this yellow suspension is added dropwise 33 µL (0.42 mmol) of chlororacetyl chloride. The reaction mixture turns clear after a few minutes and is allowed to stir at 23°C for 1h. To the reaction is added a DMSO (1 mL) solution containing 180 µL (1.4 mmol) of N,N',N' trimethylethelyenediamine. The reaction is then warmed to 60°C and stirred for 18h. The product is isolated by preparative RP-HPLC (NH₄OAc/ACN) gradient, the appropriate fractions were pooled and lyophilize to give a solid yellow as the acetic acid salt: 59 mg (51%). ¹H-NMR (400 MHz, CDCL₃): δ 10.1 (br s, 1H), 8.37 (br s, 2H), 8.18 (d, 1H), 7.97 (d, 1H), 7.60 (br d, 1H), 7.27 (s, 2H), 7.20 (br s, 3H), 6.15 (s, 1H), 3.82 (m, 2H), 3.65 (s, 6H), 3.20 (br m, 2H), 2.82 (br s, 8H), 2.42 (s, 3H), 2.02 (s, 3H). MS (EI) m/z for C₂₈H₃₄N₈O₅S: 595.84 (MH⁺).

[0330] The following title compounds were prepared using similar procedures to those in Example 156.
Example 157: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-((3-(dimethylamino)propyl)(methyl)amino)acetamide. MS (EI) m/z for C₃₀H₃₇N₇O₅S: 608.1 (MH⁺).
Example 158: 2-(1,4'-bipiperidin-1'-yl)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z for C₃₄H₄₁N₇O₅S: 660.1 (MH⁺).
Example 159: tert-butyl 2-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenylcarbamoyl)piperidine-1-carboxylate. MS (EI) m/z for C₃₃H₃₈N₆O₇S: 663.1 (MH⁺).
Example 160: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(1-(dimethylamino)propan-2-yl)benzamide. MS (EI) m/z for C₂₇H₂₉ ClN₆O₄S: 569.0 (MH⁺).
Example 161: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-ureidobenzenesulfonamide. MS (EI) m/z for C₂₃H₂₂N₆O₅S: 495.40 (MH⁺).
Example 162: 2-(dimethylamino)-N-(3-(N-(3-(5-methoxy-2-methylphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z for C₂₆H₂₈N₆O₄S: 521.69 (MH⁺).
Example 163: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-methylpiperazin-1-yl)acetamide. MS (EI) m/z for C₂₉H₃₃N₇O₅S: 592.61 (MH⁺).
Example 164: 2-acetamido-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z for C₂₆H₂₆N₆O₆S: 550.59 (MH⁺).
Example 165: tert-butyl 2-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenylamino)-2-oxoethylcarbamate. MS (EI) m/z for C₂₉H₃₂N₆O₇S: 609.32 (MH⁺).

Example 166

N-(2-(3,5-dimethoxy-phenylamino)pyrido[2,3-b]pyrazin-3-yl)-3-nitrobenzenesulfonamide

[0331] 

[0332] To a xylene suspension (15 mL) of N-(2-chloropyrido[2,3-b]pyrazin-3-yl)-3-nitrobenzenesulfonamide (1 g, 2.7 mmol) (prepared using procedures similar to those in Asier, et al J. Org Chem 2005, 70(7), 2878 and Leeson, et al J. Med.Chem 1991, 34, 1243) was added 420 mg (2.7 mmol) of 3,5 dimethoxyaniline. After refluxing the reaction for 1h, the reaction is cooled, the precipitate is collected by filtration and dried under vacumn to give 830 mg of the product as a ∼6:1 mixture of isomers with the major being N-(2-(3,5-dimethoxy-phenylamino)pyrido[2,3-b]pyrazin-3-yl)-3-nitrobenzenesulfonamide which was assigned by known chemical reactivity. Analytical HPLC, ret. time = 3.3 min (14%), 3.05 min (86%), (conditions: Phenomenex Gemini C 18 50x4.6 column, gradient 5% to 95% MeCN/H₂O, in the presence of 0.1% TFA, 5 min run at 3.5 ml/min flow rate, λ=254 nm). ¹H-NMR (400 MHz, DMSO-d6): major isomer δ 9.14 (br s, 1H), 8.69 (dd, 1H), 8.60 (dd, 1H), 8.33 (dt, 2H), 7.77 (t, 1H), 7.49 (dd, 1H), 7.37 d, 2H), 7.05 (s, 1H), 6.26 (t, 1H), 3.77 (s, 6H); MS (EI) m/z for C₂₁H₁₈N₆O₆S: 483.08 (MH⁺).

Example 167

3-amino-N-(2-(3,5-dimethoxy-phenylamino)pyrido[2,3-b]pyrazin-3-yl)benzenesulfonamide.

[0333] To a 1:1 THF/EtOH suspension (1 mL) of N-(3-(3,5-dimethoxyphenylamino)-pyrido[3,2-b]pyrazin-2-yl)-3-nitrobenzenesulfonamide (190 mg, 0.21 mmol) (prepared using procedures similar to those in Examples 166) was added 47 µL (1.26 mmol) of formic acid plus 99 mg (1.17 mmol) of potassium formate and 50 mg of 10% palladium on charcoal. After refluxing the reaction for 1h, hot filtration through celite (washing with a small portion of DMF), dilution with 30 mL of water, the pH was adjusted to 5.5 with 5% NaHCO₃, the product is isolated as a precipitate 140 mg (80%) of white powder. Analytical HPLC, ret. time = 2.6 min (90%), 3.05 min (10%), 100% pure (conditions: YMC C 18 5x4.6 column, gradient 10% to 90% MeCN/H₂O, in the presence of 0.1% TFA, 9 min run at 1 ml/min flow rate, λ =254 nm). ¹H-NMR (400 MHz, CDCL₃): δ 8.48 (br s, 1H), 8.34 (dd, 1H), 7.92 (dd, 1H), 7.41 (dd, 1H), 7.15 (m, 3H), 7.13 (d, 2H), 6.86 (dd, I H), 6. 28 (t, 1H), 3.83 (s, 6H); MS (EI) m/z for C₂₁H₂₀N₆O₄S: 453.03 (MH⁺).

Example 168

3-amino-N-(3-{[3,5-bis(methoxy)phenyl]amino}pyrido[2,3-b]pyrazin-2-yl)benzenesulfonamide

[0334] 

[0335] To a 1:1 THF/EtOH suspension (1 mL) of 3-nitro-N-(3-{[3,5-bis(methoxy)-phenyl]amino}pyrido[2,3-b]pyrazin-2-yl)benzenesulfonamide (100 mg, 0.21 mmol) (prepared using procedures similar to those used in Example 166) was added 46 µL (0.63 mmol) of formic acid plus 100mg (0.63 mmol) of potassium formate and 100 mg of 10% palladium on charcoal. After refluxing the reaction for 1h, hot filtration through celite, and concentration, the product is isolated by preparative RP-HPLC (NH₄OAc/ACN) gradient. The appropriate fractions were pooled and lyophilize to give solid yellow product: 3.2 mg (4%). ¹H-NMR (400 MHz, CDCl₃): δ 8.62 (d, 1H), 8.52 (s, 1H), 7.62 (d, 1H), 7.3 (m, 4H), 7.18 (d, 2H), 6.88 (d, 1H), 6.27 (t, 1H), 3.96 (br s, 2H), 3.83 (s, 6H). MS (EI) m/z for C₂₁H₂₀N₆O₄S: 453.22 (MH⁺).

Example 169

N-(3-{[2-chloro-5-(methoxy)phenyl]amino}quinoxalin-2-yl)-3-(1-{[2-(dimethylamino)-ethyl]amino}ethyl)benzenesulfonamide trifluoracetic acid salt

[0336] 

[0337] To a dichloroethane solution (0.6 mL) of 3-acetyl-N-(3-{[2-chloro-5-(methoxy)-phenyl]amino}quinoxalin-2-yl)benzenesulfonamide (150 mg, 0.31 mmol), prepared using procedures similar to those in Example 115, and 51 µL (0.37 mmol) of N,N-dimethylethylenediamine was added 19 µL of acetic acid followed by 132 mg (0.62 mmol) of sodium cyanoborohydride. The reaction mixture was refluxed for 18h under a nitrogen atmosphere. After concentration (in vacuo), the product is isolated by preparative RP-HPLC (0.1 % TFA/ACN) gradient, followed by lyophilization of appropriate fractions to give solid yellow solid: 189 mg (90%). ¹H-NMR (400 MHz, d₃-MeOD): δ 8.74 (s, 1H), 8.18 (s, 1H), 8.12 (d, 1H), 7.71 (m, 3H), 7.48 (m, 4H), 7.28 (d, 1H), 6.63 (d, 1H), 4.38 (q, 1H), 3.80 (s, 3H), 3.30 (m, 3H), 3.12 (m, 1H), 2.84 (s, 3H), 1.60 (d, 3H). MS (EI) m/z for C₂₇H₃₁ClN₆O₃S: 555.56 (MH⁺).

Example 170

N,N-{[(3-{[(3-{[2-chloro-5-(methoxy)phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}-4-methylphenyl)amino](dimethylamino)methylidene}-N-methylmethanaminium

[0338] 

[0339] To a dimethylformamide solution (1 mL) of 3-amino-N-(3-{[2-chloro-5-(methoxy)-phenyl]amino}quinoxalin-2-yl)2-methylbenzenesulfonamide (200 mg, 0.40 mmol), prepared using procedures similar to those described in Example 115, is added 312 µL (1.8 mmol) of DIEA and 122 mg (0.6 mmol) of HATU. After stirring for 18h at 60 °C, the product was precipitated from a 1:1 mixture of hexane/ethyl acetate, filtered and dried to afford 60 mg (26%). ¹H NMR (400 MHz, DMSO-d₆): δ 9.26 (b rs, 1H), 8.96 (br s, 1H), 7.80 (s, 1H), 7.51 (br s, 1H), 7.45 (d, 1H), 7.18 (brm, 4H), 6.91 (br s, 1H), 6.60 (br d, 1H), 3.82 (s, 3H), 3.36 (s, 3H), 2.85 (s, 6H), 2.58 (s, 3H). MS (EI) m/z for C₂₇H₃₁ClN₇O₃S⁺: 569.32 (MH⁺).

Example 171

2-Bromo-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide

[0340] 

[0341] In a 50 mL round-bottom flask was added 2-bromoacetic acid (1.87 g, 13.5 mmol), N,N-diisopropylcarbodiimide (860 mg, 6.8 mmol) and 10 mL DCM. To this mixture was added 3-amino-N-(3-(3,5-dimethoxyphenylamino) quinoxalin-2-yl) benzenesulfonamide (2.03 g, 4.5 mmol), prepared using procedures similar to those in Example 168. The reaction was stirred overnight at room temperature. Complete consumption of the starting aniline was confirmed by LCMS. The solvent was evaporated off to yield the crude product (2-bromo-N-(3-(N-(3-(3,5-dimethoxyphenylamino) quinoxalin-2-yl)sulfamoyl) phenyl) acetamide). This was used directly in the next step without purther purification.

General Alkylation Procedure 1

[0342] 

[0343] Into a 2-dram vial was placed 2-bromo-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl) sulfamoyl) phenyl) acetamide (86 mg, 0.15 mmol), prepared using procedures similar to those in Example 171,along with 2 mL of acetonitrile. Eight equivalents (1.2 mmol) of the desired amine, aniline, hydrazine or alkoxyamine were added followed by the addition of Hunig's Base (41 µL, 0.25 mmol). The reaction then was stirred at 50 °C for one hour (overnight for aniline reagents). Preparative reverse-phase HPLC was used to isolate the desired product directly from the crude reaction mixture. A Waters Fractionlynx preparative reverse-phase HPLC-equipped with a Waters SunFire Prep C18, OCD 5 µM, 30 X 70 mm column and running a 5-100 % gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile - was used to carry out the purification.

[0344] The following title compounds were prepared according to General Library Alkylation Procedure 1.
Example 172: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methylamino)acetamide. ¹H-NMR (400MHz, d₆-DMSO): 8.81 (s, 1H), 8.23 (t, 1H), 7.75 (d, 1H), 7.66 (d, 1H), 7.41-7.38 (m, 1H), 7.35 (m, 1H), 7.32 (d, 2H), 7.29-7.27 (m, 1H), 7.14-7.11 (m, 2H), 6.14 (t, 1H), 3.80 (s, 1H), 3.78 (s, 6H), 2.58 (s, 3H), 1.91 (s, 2H); MS (EI) m/z C₂₅H₂₆N₆O₅S: 523.6 (MH⁺).
Example 173: 2-(cyclopropylmethylamino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. ¹H-NMR (400MHz, d₆-DMSO): 10.58 (s, 1H), 8.81 (s, 1H), 8.20 (t, 1H), 7.76 (d, 1H), 7.67 (d, 1H), 7.42-7.36 (m, 2H), 7.32 (d, 2H), 7.27 (s, 1H), 7.14-7.12 (m, 2H), 6.15 (t, 1H), 3.93 (s, 2H), 3.78 (s, 6H), 2.89 (s, 1H), 2.88 (s, 1H), 1.05-1.00 (m, 1H), 0.59 (d, 1H), 0.57 (d, 1H), 0.35 (d, 1H), 0.34 (d, 1H); MS (EI) m/z C₂₈H₃₀N₆0₅S: 563.6 (MH⁺).
Example 174: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-hydroxy-propylamino)acetamide. ¹H-NMR (400MHz, d₆-DMSO): 10.49 ppm (s, 1H), 8.81 ppm (s, 1H), 8.23 ppm (t, 1H), 8.13 ppm (s, 1H), 7.76 ppm (d, 1H), 7.765-7.763 (dd, 1H), 7.41-7.37 ppm (m, 2H), 7.33-7.32 ppm (d, 1H), 7.30-7.28 ppm (m, 1H), 7.16-7.09 ppm (m, 2H), 6.55 ppm (s, 1H), 6.14 ppm (t, 1H), 5.49 ppm (d, 2H), 5.25 ppm (s, 1H), 3.85 ppm (s, 1H), 3.78 ppm (s, 6H) 3.67-3.59 ppm (m, 1H), 3.00-2.89 ppm (dd, 1H), 2.79-2.76 ppm (m, 1H), 1.10 ppm (d, 1H), 1.01-0.99 ppm (d, I H); MS (EI) m/z C₂₇H₃₀N₆O₆S: 566.6 (MH⁺).
Example 175: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)2-(3-fluorobenzylamino)acetamide. ¹H-NMR (400MHz, d₆-DMSO): 10.42 ppm (s, 1H), 8.82 ppm (s, 1H), 8.23 ppm (s, 1H), 8.14 ppm (s, 1H), 7.75 ppm (d, 1H), 7.65 ppm (d, 1H), 7.49-7.32 ppm (m, 6H), 7.25-7.20 ppm (m, 1H), 7.14-7.12 ppm (m, 2H), 6.55 ppm (s, 1H), 6.15 ppm (t, 1H), 4.14 ppm (s, 2H), 3.78 ppm (s, 6H), 3.74 ppm (s, 2H); MS (EI) m/z C₃₁H₂₉FN₆O₅S: 616.7 (MH⁺).
Example 176: 2-(benzylamino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₁H₃₀N₆O₅S: 599 (MH⁺).
Example 177: 2-(diethylamino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₂₈H₃₂N₆O₅S: 565 (MH⁺).
Example 178: 2-(4-(3,4-dichlorophenyl)piperazin-1-yl)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₄H₃₃Cl₂N₇O₅S: 722 (MH⁺).
Example 179: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2,2-dimethylhydrazinyl)acetamide. MS (EI) m/z C₂₆H₂₉N₇O₅S: 552 (MH⁺).
Example 180: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(p-tolylamino)acetamide. MS (EI) m/z C₃₁H₃₀N₆O₅S: 599 (MH⁺).

[0345] Example 181: 2-(benzyloxyamino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₁H₃₀N₆O₆S: 615 (MH⁺).

[0346] Example 182: 2-(2-chlorophenylamino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₀H₂₇ClN₆O₅S: 619 (MH⁺).
Example 183: N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(isopropylamino)acetamide. MS (EI) m/z C₂₇H₃₀N₆O₅S: 551 (MH⁺).
Example 184: 2-(4-cyclopentylpiperazin-1-yl)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₃H₃₉N₇O₅S: 646 (MH⁺).
Example 185: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-propylpiperidin-1-yl)acetamide. MS (EI) m/z C₃₂H₃₈N₆O₅S: 619 (MH⁺).
Example 186: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(isobutoxyamino)acetamide. MS (EI) m/z C₂₈H₃₂N₆O₆S: 581 (MH⁺).
Example 187: 2-(3-tert-butylphenylamino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₄H₃₆N₆O₅S: 641 (MH⁺).
Example 188: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-phenylpropan-2-ylamino)acetamide. MS (EI) m/z C₃₃H₃₄N₆O₅S: 627 (MH⁺).
Example 189: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-fluoro-4-hydroxyphenylamino)acetamide. MS (EI) m/z C₃₀H₂₇FN₆O₆S: 619 (MH⁺).
Example 190: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-(methylthio)benzylamino)acetamide. MS (EI) m/z C₃₂H₃₂N₆O₅S₂: 645 (MH⁺).
Example 191: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(5-fluoro-2-methylbenzylamino)acetamide. MS (EI) m/z C₃₂H₃₁FN₆O₅S: 631 (MH⁺).
Example192: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-phenylpyrrolidin-1-yl)acetamide. MS (EI) m/z C₃₄H₃₄N₆O₅S: 639 (MH⁺).
Example 193: 2-(2-benzylpyrrolidin-1-yl)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₅H₃₆N₆O₅S: 653 (MH⁺).
Example 194: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-phenylmorpholino)acetamide. MS (EI) m/z C₃₄H₃₄N₆O₆S: 655 (MH⁺).
Example 195: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-(pyridin-4-yl)piperidin-1-yl)acetamide. MS (EI) m/z C₃₄H₃₅N₇O₅S: 654 (MH⁺).
Example 196: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(o-tolylamino)acetamide. MS (EI) m/z C₃₁H₃₀N₆O₅S: 599 (MH⁺).
Example 197: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2,4-dimethylbenzylamino)acetamide. MS (EI) m/z C₃₃H₃₄N₆O₅S: 627 (MH⁺).
Example 198: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methyl(pyridin-3-ylmethyl)amino)acetamide. MS (EI) m/z C₃₁H₃₁N₇O₅S: 614 (MH⁺).
Example 199: 2-(3-chloro-4-methylbenzylamino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₂H₃₁ClN₆O₅S: 647 (MH⁺).
Example 200: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-((2-(dimethylamino)-ethyl)(methyl)amino)acetamide. MS (EI) m/z C₂₉H₃₅N₇O₅S: 594 (MH⁺).
Example 201: 2-(4-acetylpiperazin-1-yl)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₀H₃₃N₇O₆S: 620 (MH⁺).
Example 202: N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(methyl(1-methylpyrrolidin-3-yl)amino)acetamide. MS (EI) m/z C₃₀H₃₅N₇O₅S: 606 (MH⁺).
Example 203: N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-methyl-1,4-diazepan-1-yl)acetamide. MS (EI) m/z C₃₀H₃₅N₇O₅S: 606 (MH⁺).
Example 204: 2-(4-allylpiperazin-1-yl)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₁H₃₅N₇O₅S: 618 (MH⁺).
Example 205: N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-isopropylpiperazin-1-yl)acetamide MS (EI) m/z C₃₁H₃₇N₇O₅S: 620 (MH⁺).
Example 206: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-(dimethylamino)pyrrolidin-1-yl)acetamide. MS (EI) m/z C₃₀H₃₅N₇O₅S: 606 (MH⁺).
Example 207: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-(dimethylamino)azetidin-1-yl)acetamide. MS (EI) m/z C₂₉H₃₃N₇O₅S: 592 (MH⁺).
Example 208: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-oxopiperidin-1-yl)acetamide. MS (EI) m/z C₂₉H₃₀N₆O₆S: 591 (MH⁺).
Example 209: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-((2-methoxyethyl)(methyl)amino)acetamide. MS (EI) m/z C₂₈H₃₂N₆O₆S: 581 (MH⁺).
Example 210: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-methylbenzyloxyamino)acetamide. MS (EI) m/z C₃₂H₃₂N₆O₆S: 629 (MH⁺).
Example 211: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxatin-2-yl)sulfamoyl)phenyl)-2-(2-methoxybenzyloxyamino)acetamide. MS (EI) m/z C₃₂H₃₂N₆O₇S: 645 (MH⁺).
Example 212: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(propylamino)acetamide. MS (EI) m/z C₂₇H₃₀N₆O₅S: 551 (MH⁺).
Example 213: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(ethyl(methyl)amino)acetamide. MS (EI) m/z C₂₁H₃₀N₆O₅S: 551 (MH⁺).
Example 214: 2-(allyl(methyl)amino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₂₈H₃₀N₆O₅S: 563 (MH⁺).
Example 215: 2-(tert-butylamino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₂₈H₃₂N₆O₅S: 565 (MH⁺).
Example 216: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(isobutylamino)acetamide. MS (EI) m/z C₂₈H₃₂N₆O₅S: 565 (MH⁺).
Example 217: 2-(butylamino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₂₈H₃₂N₆O₅S: 565 (MH⁺).
Example 218: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(isopropyl(methyl)amino)acetamide. MS (EI) m/z C₂₈H₃₂N₆O₅S: 565 (MH⁺).
Example 219: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-formylpiperazin-1-yl)acetamide. MS (EI) m/z C₂₉H₃₁N₇O₆S: 606 (MH⁺).
Example 220: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-ethylpiperazin-1-yl)acetamide. MS (EI) m/z C₃₀H₃₅N₇O₅S: 606 (MH⁺).
Example 221: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-formyl-1,4-diazepan-1-yl)acetamide. MS (EI) m/z C₃₀H₃₃N₇O₆S: 620 (MH⁺).
Example 222: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(ethyl(2-hydroxyethyl)amino)acetamide. MS (EI) m/z C₂₈H₃₂N₆O₆S: 581 (MH⁺).
Example 223: (S)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-hydroxypyrrolidin-1-yl)acetamide. MS (EI) m/z C₂₈H₃₀N₆O₆S: 579 (MH⁺).
Example 224: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2,6-dimethylmorpholino)acetamide. MS (EI) m/z C₃₀H₃₄N₆O₆S: 607 (MH⁺).
Example 225: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-methylbenzylamino)acetamide. MS (EI) m/z C₃₂H₃₂N₆O₅S: 613 (MH⁺).
Example 226: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-methoxy-ethylamino)acetamide. MS (EI) m/z C₂₇H₃₀N₆O₆S: 567 (MH⁺).
Example 227: N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(thiazolidin-3-yl)acetamide. MS (EI) m/z C₂₇H₂₈N₆O₅S₂: 581 (MH⁺).
Example 228: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-(hydroxymethyl)piperidin-1-yl)acetamide. MS (EI) m/z C₃₀H₃₄N₆O₆S: 607 (MH⁺).
Example 229: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-phenylpropylamino)acetamide. MS (EI) m/z C₃₃H₃₄N₆O₅S: 627 (MH⁺).
Example 230: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(isobutyl(methyl)amino)acetamide. MS (EI) m/z C₂₉H₃₄N₆O₅S: 579 (MH⁺).
Example 231: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(phenylamino)acetamide. MS (EI) m/z C₃₀H₂₈N₆O₅S: 585 (MH⁺).
Example 232: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-propylphenylamino)acetamide. MS (EI) m/z C₃₃H₃₄N₆O₅S: 627 (MH⁺).
Example 233: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-isopropylphenylamino)acetamide. MS (EI) m/z C₃₃H₃₄N₆O₅S: 627 (MH⁺).
Example 234: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-fluoro-4-methylphenylamino)acetamide. MS (EI) m/z C₃₁H₂₉FN₆O₅S: 617 (MH⁺).
Example 235: 2-(4-chlorophenylamino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₀H₂₇ClN₆O₅S: 619 (MH⁺).
Example 236: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-methoxyphenylamino)acetamide. MS (EI) m/z C₃₁H₃₀N₆O₆S: 615 (MH⁺).
Example 237: 2-(3-chlorophenylamino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₀H₂₇ClN₆O₅S: 619 (MH⁺).
Example 238: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2,3-dimethylphenylamino)acetamide. MS (EI) m/z C₃₂H₃₂N₆O₅S: 613 (MH⁺).
Example 239: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-fluorophenylamino)acetamide. MS (EI) m/z C₃₀H₂₇FN₆O₅S: 603 (MH⁺).
Example 240: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-fluorophenylamino)acetamide. MS (EI) m/z C₃₀H₂₇FN₆O₅S: 603 (MH⁺).
Example 241: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(thiophen-2-ylmethylamino)acetamide. MS (EI) m/z C₂₉H₂₈N₆O₅S₂: 605 (MH⁺).
Example 242: 2-(cyclohexyl(ethyl)amino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₂H₃₈N₆O₅S: 619 (MH⁺).
Example 243: 2-((cyclopropylmethyl)(propyl)amino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₁H₃₆N₆O₅S: 605 (MH⁺).
Example 244: 2-(allyl(cyclopentyl)amino)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₂H₃₆N₆O₅S: 617 (MH⁺).
Example 245: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(ethyl(isopropyl)amino)acetamide. MS (EI) m/z C₂₉H₃₄N₆O₅S: 579 (MH⁺).
Example 246: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(ethyl(phenyl)amino)acetamide. MS (EI) m/z C₃₂H₃₂N₆O₅S: 613 (MH⁺).
Example 247: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-methylpyrrolidin-1-yl)acetamide. MS (EI) m/z C₂₉H₃₂N₆O₅S: 577 (MH⁺).
Example 248: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-methylpiperidin-1-yl)acetamide. MS (EI) m/z C₃₀H₃₄N₆O₅S: 591 (MH⁺).
Example 249: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(pyridin-2-ylmethylamino)acetamide. MS (EI) m/z C₃₀H₂₉N₇O₅S: 600 (MH⁺).
Example 250: 2-(benzyl(methyl)amino)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₂H₃₂N₆O₅S: 613 (MH⁺).
Example 251: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(1-phenylethylamino)acetamide. MS (EI) m/z C₃₂H₃₂N₆O₅S: 613 (MH⁺).
Example 252: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-methylpiperidin-1-yl)acetamide. MS (EI) m/z C₃₀H₃₄N₆O₅S: 591 (MH⁺).
Example 253: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-methylpiperidin-1-yl)acetamide. MS (EI) m/z C₃₀H₃₄N₆O₅S: 591 (MH⁺).
Example 254: 2-(3,4-dihydroisoquinolin-2(1H)-yl)-N-(3-(N-(3-(3,5-dimethoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₃H₃₂N₆O₅S: 625 (MH⁺).
Example 255: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2,6-dimethylpiperidin-1-yl)acetamide. MS (EI) m/z C₃₁H₃₆N₆O₅S: 605 (MH⁺).
Example 256: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-hydroxybenzylamino)acetamide. MS (EI) m/z C₃₁H₃₀N₆O₆S: 615 (MH⁺).

General Library Acylation Procedure 1

[0347] 

[0348] Into a 2-dram vial were added 3-amino-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide (54 mg, 0.12 mmol), prepared using procedures similar to those described in Example 15, DMA (2 mL) and the desired carboxylic acid (0.17 mmol). DIEA (70 µL, 0.4 mmol) followed by HATU (53 mg,0.14 mmol) were added to the vial and the reaction mixture stirred at 50 °C overnight. Preparative reverse-phase HPLC was used to isolate the desired product directly from the crude reaction mixture. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18 OCD 5 µM, 30 X 70 mm column and running a 5-100 % gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification.

[0349] The following title compounds were prepared according to General Library Acylation Procedure 1.
Example 257: N-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)morpholine-4-carboxamide: MS (EI) m/z for C₂₆H₂₅ClN₆O₅S: 567 (MH^-).
Example 258: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide. MS (EI) m/z for C₂₆H₂₈N₆O₅S: 535.1 (MH^-).
Example 259: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)propionamide. ¹H-NMR (400MHz, d₆-DMSO): 12.37 (s,1H), 10.20 (s, 1H), 8.88 (s, 1H), 8.37 (s, 1H), 7.93 (s, 1H), 7.77 (t, 2H), 7.59 (t, 1H), 7.51 (t, 1H), 7.41-7.34 (m, 4H), 6.24 (t, 1H), 3.76 (s, 6H), 2.36-2.31 (dd, 2H), 1.10 (s, 1H), 1.08 (s, 1H), 1.06 (s, 1H); MS (EI) m/z C₂₅H₂₅N₅O₅S: 508.6 (MH⁺).
Example 260: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pyridazine-4-carboxamide. ¹H-NMR (400MHz, d₆-DMSO): 11.01 (s, 1H), 9.66 (dd, 1H), 9.52 (dd, 1H), 8.90 (s, 1H), 8.55 (s, 1H), 8.13 (dd, 1H), 7.99 (d, 1H), 7.93 (d, 1H), 7.65-7.58 (m, 2H), 7.42-7.35 (m, 4H), 6.24 (t, 1H), 3.75 (s, 6H); MS (EI) m/z C₂₇H₂₃N₇O₅S: 558.6 (MH⁺).
Example 261: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylnicotinamide. ¹H-NMR (400MHz, d₆-DMSO): 10.78 ppm (s, 1H), 8.90 ppm (s, 1H), 8.58-8.57 ppm (dd, 2H), 7.90-7.86 (m, 4H), 7.60-7.56 ppm (m, 2H), 7.42-7.34 (m, 5H), 6.23 ppm (t, 1H), 3.74 ppm (s, 6H), 2.57 ppm (s, 3H); MS (EI) m/z C₂₉H₂₆N₅O₅S: 570.6 (MH⁺).
Example 262: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(o-tolyloxy)acetamide. ¹H-NMR (400MHz, d₆-DMSO): 12.37 ppm (s, 1H), 10.41 ppm (s, 1H), 8.90 ppm (s, 1H), 8.41 ppm (s, 1H), 7.93 ppm (s, 1H), 7.90-7.8 (m, 2H), 7.59-7.53 ppm (m, 2H), 7.42-7.33 ppm (m, 4H), 7.17-7.12 ppm (m, 2H), 6.89-6.85 ppm (m, 2H), 6.24 ppm (t, 1H), 4.74 ppm (s, 2H), 3.76 ppm (s, 6H), 2.33 ppm (s, 2H); MS (EI) m/z C₃₁H₂₉N₅O₆S: 599.7 (MH⁺).
Example 263: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-methoxy-4-methylbenzamide. MS (EI) m/z C₃₁H₂₉N₅O₆S: 600 (MH⁺).
Example 264: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-methoxy-4-methylbenzamide. MS (EI) m/z C₂₈H₂₄N₆O₅S: 557 (MH⁺).
Example 265: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)thiazole-4-carboxamide. MS (EI) m/z C₂₆H₂₂N₆O₅S₂: 563 (MH⁺).
Example 266: 2-bromo-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)thiophene-3-carboxamide. MS (EI) m/z C₂₇H₂₂BrN₅O₅S₂ 640 (MH⁺).
Example 267: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pivalamide. MS (EI) m/z C₂₇H₂₉N₅O₅S: 536 (MH⁺).
Example 268: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pent-4-enamide. MS (EI) m/z C₂₇H₂₇N₅O₅S: 534 (MH⁺).
Example 269: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide. MS (EI) m/z C₂₉H₂₅N₅O₅S: 556 (MH⁺).
Example 270: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)butyramide. MS (EI) m/z C₂₆H₂₇N₅O₅S: 522 (MH⁺).
Example 271: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methoxyacetamide. MS (EI) m/z C₂₅H₂₅N₅O₆S: 524 (MH⁺).
Example 272: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)cyclobutanecarboxamide. MS (EI) m/z C₂₇H₂₇N₅O₅S: 534 (MH⁺).
Example 273: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylcyclopropanecarboxamide. MS (EI) m/z C₂₇H₂₇N₅O₅S: 534 (MH⁺).
Example 274: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-methylcyclopropanecarboxamide. MS (EI) m/z C₂₇H₂₇N₅O₅S: 534 (MH⁺).
Example 275: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-methylbutanamide. MS (EI) m/z C₂₇H₂₉N₅O₅S: 536 (MH⁺).
Example 276: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-ethoxyacetamide. MS (EI) m/z C₂₆H₂₇N₅O₆S: 538 (MH⁺). Example 277: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-methoxypropanamide. MS (EI) m/z C₂₆H₂₇N₅O₆S: 538
(MH⁺).
Example 278: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-hydroxyacetamide. MS (EI) m/z C₂₄H₂₃N₅O₆S: 510 (MH⁺).
Example279: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)isobutyramide. MS (EI) m/z C₂₆H₂₇N₅O₅S: 522 (MH⁺).
Example 280: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-hydroxycyclopropanecarboxamide. MS (EI) m/z C₂₆H₂₅N₅O₆S: 536 (MH⁺).
Example 281: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)furan-3-carboxamide. MS (EI) m/z C₂₇H₂₃N₅O₆S: 546 (MH⁺).
Example 282: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)tetrahydrofuran-3-carboxamide. MS (EI) m/z C₂₇H₂₇N₅O₆S: 550 (MH⁺).
Example 283: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)tetrahydrofuran-2-carboxamide. MS (EI) m/z C₂₇H₂₇N₅O₆S: 550 (MH⁺).
Example 284: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)furan-2-carboxamide. MS (EI) m/z C₂₇H₂₃N₅O₆S: 546 (MH⁺).
Example 285: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)isonicotinamide. MS (EI) m/z C₂₈H₂₄N₆O₅S: 557 (MH⁺).
Example 286: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1H-pyrrole-2-carboxamide. MS (EI) m/z C₂₇H₂₄N₆O₅S: 545 (MH⁺).
Example 287: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pyrazine-2-carboxamide. MS (EI) m/z C₂₇H₂₃N₇O₅S: 558 (MH⁺).
Example 288: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-methyl-1H-pyrrole-2-carboxamide. MS (EI) m/z C₂₈H₂₆N₆O₅S: 559 (MH⁺).
Example 289: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-5-methylisoxazole-3-carboxamide. MS (EI) m/z C₂₇H₂₄N₆O₆S: 561 (MH⁺).
Example 290: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)thiophene-2-carboxamide. MS (EI) m/z C₂₇H₂₃N₅O₅S₂: 562 (MH⁺).
Example 291: (S)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-methylpyrrolidine-2-carboxamide. MS (EI) m/z C₂₈H₃₀N₆O₅S: 563 (MH⁺).
Example 292: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylbenzamide. MS (EI) m/z C₃₀H₂₇N₅O₅S: 570 (MH⁺).
Example 293: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-phenylacetamide. MS (EI) m/z C₃₀H₂₇N₅O₅S: 570 (MH⁺).
Example 294: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-methylpicolinamide. MS (EI) m/z C₂₉H₂₆N₆O₅S: 571 (MH⁺).
Example 295: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(pyridin-3-yl)acetamide. MS (EI) m/z C₂₉H₂₆N₆O₅S: 571 (MH⁺).
Example 296: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-6-hydroxypicolinamide. MS (EI) m/z C₂₈H₂₄N₆O₆S: 573 (MH⁺).
Example 297: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-fluorobenzamide MS (EI) m/z C₂₉H₂₄FN₅O₅S: 574 (MH⁺).
Example 298: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-fluorobenzamide. MS (EI) m/z C₂₉H₂₄FN₅O₅S: 574 (MH⁺).
Example 299: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-fluorobenzamide. MS (EI) m/z C₂₉H₂₄FN₅O₅S: 574 (MH⁺).
Example 300: 2-cyclohexyl-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₀H₃₃N₅O₅S: 576 (MH⁺).
Example 301: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-oxocyclopentyl)acetamide. MS (EI) m/z C₂₉H₂₉N₅O₆S: 576 (MH⁺).
Example 302: 4-cyclopropyl-N-(3-(N-(3-(3,5-dlmethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-oxobutanamide. MS (EI) m/z C₂₉H₂₉N₅O₆S: 576 (MH⁺).
Example 303: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-oxocyclohexanecarboxamide. MS (EI) m/z C₂₉H₂₉N₅O₆S: 576 (MH⁺).
Example 304: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-(pyridin-3-yl)propanamide. MS (EI) m/z C₃₀H₂₈N₆O₅S: 585 (MH⁺).
Example 305: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methoxybenzamide. MS (EI) m/z C₃₀H₂₇N₅O₆S: 586 (MH⁺).
Example 306: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-methoxybenzamide. MS (EI) m/z C₃₀H₂₇N₅O₆S: 586 (MH⁺).
Example 307: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-phenoxyacetamide. MS (EI) m/z C₃₀H₂₇N₅O₆S: 586 (MH⁺).
Example 308: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-methoxybenzamide. MS (EI) m/z C₃₀H₂₇N₅O₆S: 586 (MH⁺).
Example 309: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-fluorophenyl)acetamide. MS (EI) m/z C₃₀H₂₆FN₅O₅S: 588
(MH⁺).
Example 310: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-fluorophenyl)acetamide. MS (EI) m/z C₃₀H₂₆FN₅O₅S: 588 (MH⁺).
Example 311: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-fluorophenyl)acetamide. MS (EI) m/z C₃₀H₂₆FN₃O₅S: 588 (MH⁺).
Example 312: 2-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide. MS (EI) m/z C₂₉H₂₄ClN₅O₅S: 590 (MH⁺).
Example 313: 4-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide. MS (EI) m/z C₂₉H₂₄ClN₅O₅S: 590 (MH⁺).
Example 314: 3-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide. MS (EI) m/z C₂₉H₂₄ClN₅O₅S: 590 (MH⁺).
Example 315: (1R,2R)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-phenylcyclopropanecarboxamide. MS (EI) m/z C₃₂H₂₉N₅O₅S: 596 (MH⁺).
Example 316: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-phenylcyclopropanecarboxamide. MS (EI) m/z C₃₂H₂₉N₅O₅S: 596 (MH⁺).
Example 317: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(1H-imidazol-4-yl)acetamide. MS (EI) m/z C₂₇H₂₅N₇O₅S: 560 (MH⁺).
Example 318: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-methoxy-2-methylbenzamide. MS (EI) m/z C₃₁H₂₉N₅O₆S: 600 (MH⁺).
Example 319: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-fluorophenoxy)acetamide. MS (EI) m/z C₃₀H₂₆FN₅O₆S: 604 (MH⁺).
Example 320: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-5-fluoro-2-methoxybenzamide. MS (EI) m/z C₃₀H₂₆FN₅O₆S: 604 (MH⁺).
Example 321: 2-(4-chlorophenyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₀H₂₆ClN₅O₅S: 604 (MH⁺).
Example 322: 2-(2-chlorophenyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₀H₂₆ClN₅O₅S: 604 (MH⁺).
Example 323: 2-(3-chlorophenyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₃₀H₂₆ClN₅O₅S: 604 (MH⁺).
Example 324: 1-acetyl-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)piperidine-4-carboxamide. MS (EI) m/z C₃₀H₃₂N₆O₆S: 605 (MH⁺).
Example 325: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(pyridin-4-yl)acetamide. MS (EI) m/z C₂₉H₂₆N₆O₅S: 571 (MH⁺).
Example 326: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(pyridin-2-yl)acetamide. MS (EI) m/z C₂₉H₂₆N₆O₅S: 571 (MH⁺).
Example 327: 2,4-dichloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide. MS (EI) m/z C₂₉H₂₃Cl₂N₅O₅S: 624 (MH⁺).
Example 328: 3,4-dichloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide. MS (EI) m/z C₂₉H₂₃Cl₂N₅O₅S: 624 (MH⁺).
Example 329: 2,5-dichloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide. MS (EI) m/z C₂₉H₂₃Cl₂N₅O₅S: 624 (MH⁺).
Example 330: 3,5-dichloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide. MS (EI) m/z C₂₉H₂₃Cl₂N₅O₅S: 624 (MH⁺).
Example 331: 2,3-dichloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamlno)quinoxalin-2-yl)sulfamoyl)phenyl)benzamide. MS (EI) m/z C₂₉H₂₃Cl₂N₅O₅S: 624 (MH⁺).
Example 332: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pentanamide. MS (EI) m/z C₂₇H₂₉N₅O₅S: 536 (MH⁺).
Example 333: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylbutanamide. MS (EI) m/z C₂₇H₂₉N₅O₅S: 536 (MH⁺).
Example 334: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1H-imidazole-2-carboxamide. MS (EI) m/z C₂₆H₂₃N₇O₅S: 546 (MH⁺).
Example 335: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1H-imidazole-4-carboxamide. MS (EI) m/z C₂₆H₂₃N₇O₅S: 546 (MH⁺).
Example 336: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)isoxazole-5-carboxamide. MS (EI) m/z C₂₆H₂₂N₆O₆S: 547 (MH⁺).
Example 337: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3,3-dimethylbutanamide. MS (EI) m/z C₂₈H₃₁N₅O₅S: 550 (MH⁺).
Example 338: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methylpentanamide. MS (EI) m/z C₂₈H₃₁N₅O₅S: 550 (MH⁺).
Example 339: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2,2-dimethylbutanamide. MS (EI) m/z C₂₈H₃₁N₅O₅S: 550 (MH⁺).
Example 340: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-methylpentanamide. MS (EI) m/z C₂₈H₃₁N₅O₅S: 550 (MH⁺).
Example 341: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)pyrimidine-5-carboxamide. MS (EI) m/z C₂₇H₂₃N₇O₅S: 558 (MH⁺).
Example 342: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-methylfuran-2-carboxamide. MS (EI) m/z C₂₈H₂₅N₅O₆S: 560 (MH⁺).
Example 343: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)thiophene-3-carboxamide. MS (EI) m/z C₂₇H₂₃N₅O₅S₂: 562 (MH⁺).
Example 344: N-(3-(N-(3-(3,5,dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-oxocyclopentanecarboxamide. MS (EI) m/z C₂₈H₂₇N₅O₆S: 562 (MH⁺).
Example 345: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-methoxyethoxy)acetamide. MS (EI) m/z C₂₇H₂₉N₅O₇S: 568 (MH⁺).
Example 346: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-methylbenzamide. MS (EI) m/z C₃₀H₂₇N₅O₅S: 570 (MH⁺).
Example 347: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl-2-(3-methylisoxazol-4-yl)acetamide. MS (EI) m/z C₂₈H₂₆N₆O₆S: 575 (MH⁺).
Example 348: 3-cyclopentyl-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)propanamide. MS (EI) m/z C₃₀H₃₃N₅O₅S: 576 (MH⁺).
Example 349: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-o-tolylacetamide. MS (EI) m/z C₃₁H₂₉N₅O₅S: 584 (MH⁺).
Example 350: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methoxynicotinamide. MS (EI) m/z C₂₉H₂₆N₆O₆S: 587 (MH⁺).
Example 351: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-fluoro-3-methylbenzamide. MS (EI) m/z C₃₀H₂₆FN₅O₅S: 588 (MH⁺).
Example 352: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-fluoro-2-methylbenzamide. MS (EI) m/z C₃₀H₂₆FN₅O₅S: 588 (MH⁺).
Example 353 : N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-fluoro-4-methylbenzamide. MS (EI) m/z C₃₀H₂₆FN₅O₅S: 588 (MH⁺).
Example 354: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-fluoro-5-methylbenzamide. MS (EI) m/z C₃₀H₂₆FN₅O₅S: 588 (MH⁺).
Example 355: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-5-fluoro-2-methylbenzamide. MS (EI) m/z C₃₀H₂₆FN₅O₅S: 588 (MH⁺).
Example 356: 6-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)nicotinamide. MS (EI) m/z C₂₈H₂₃ClN₆O₅S: 591 (MH⁺).
Example 357: 2-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)nicotinamide. MS (EI) m/z C₂₈H₂₃ClN₆O₅S: 591 (MH⁺).
Example 358: 2-chloro-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)isonicotinamide. MS (EI) m/z C₂₈H₂₃ClN₆O₅S: 591 (MH⁺).
Example 359: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-4-(dimethylamino)benzamide. MS (EI) m/z C₃₁H₃₀N₆O₅S: 599 (MH⁺).
Example 360: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-(dimethylamino)benzamide. MS (EI) m/z C₃₁H₃₀N₆O₅S: 599 (MH⁺).
Example 361: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)benzo[d][1,3]dioxole-5-carboxamide. MS (EI) m/z C₃₀H₂₅N₅O₇S: 600 (MH⁺).
Example 362: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(m-tolyloxy)acetamide. MS (EI) m/z C₃₁H₂₉N₅O₆S: 600 (MH⁺).
Example 363: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(4-methoxyphenyl)acetamide. MS (EI) m/z C₃₁H₂₉N₅O₆S: 600 (MH⁺).
Example 364: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(2-methoxyphenyl)acetamide. MS (EI) m/z C₃₁H₂₉N₅O₆S: 600 (MH⁺).
Example 365: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(3-methoxyphenyl)acetamide. MS (EI) m/z C₃₁H₂₉N₅O₆S: 600 (MH⁺).
Example 366: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-methoxy-4-methylbenzamide. MS (EI) m/z C₃₁H₂₉N₅O₆S: 600 (MH⁺).
Example 367: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-fluoro-4-methoxybenzamide. MS (EI) m/z C₃₀H₂₆FN₅O₆S: 604 (MH⁺).
Example 368: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-fluoro-6-methoxybenzamide. MS (EI) m/z C₃₀H₂₆FN₅O₆S: 604 (MH⁺).
Example 369: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-(4-methoxyphenyl)propanamide. MS (EI) m/z C₃₂H₃₁N₅O₆S: 614 (MH⁺).
Example 370: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-(2-methoxyphenyl)propanamide. MS (EI) m/z C₃₂H₃₁N₅O₆S: 614 (MH⁺).
Example 371: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-3-(3-methoxyphenyl)propanamide. MS (EI) m/z C₃₂H₃₁N₅O₆S: 614 (MH⁺).

Example 372

N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide.

[0350] 

[0351] Into a 20 mL vial was added 3-amino-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide (0.24 mmol, 1 equiv), prepared using procedures similar to those described in Example 15, DMA (5 mL) and 1-(tert-butoxycarbonyl)azetidine-3-carboxylic acid (0.336 mmol, 1.4 equiv). Hunig's Base (0.792 mmol, 3.3 equiv) and HATU (0.288 mmol, 1.2 equiv) were added to the vial and the reaction mixture was then stirred at room temperature overnight. Completion of the reaction was indicated by LCMS. The solvent was removed by rotary evaporation. The crude mixture was carried forward without further purification. The residue was suspended in 5 mL ethyl acetate and chilled in an ice bath. A solution of 4 N HCl in dioxane (3 mL, 5 equiv) was added with stirring. The reaction mixture was then stirred at room temperature overnight. The solid materials were collected by filtration, washed with ethylacetate then purified further by preparative reverse-phase HPLC (ammonium acetate/ACN). A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C 18, OCD 5 µM, 30 X 70 mm column and running a 5-100 % gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification. N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide was obtained (26 mg, 20%). ¹H-NMR (400MHz, d₆-DMSO): 10.26 (s, 1H), 8.81 (s, 1H), 8.25 (t, 1H), 8.14 (s, 1H), 7.74 (d, 1H), 7.69 (d, 1H), 7.41-7.39 (m, 1H), 7.36 (d, 1H), 7.32 (d, 2H), 7.30-7.28 (dd, 1H), 7.14-7.11 (m, 2H), 6.14 (t, 1H), 4.09 (d, 4H), 3.78 (s, 6H); MS (EI) m/z C₂₆H₂₆N₆0₅S: 535.6 (MH⁺).

Example 373

N-(3-(4-fluorophenylamino)quinoxalin-2-yl)benzenesulfonamide

[0352] 

[0353] A flask was charged with 2,3-dichloroquinoxaline (3.5 g, 18 mmol), 85 mL of dimethylsulfoxide, benzene sulfonamide (2.8 g, 18 mmol), and cesium carbonate (5.8 g, 18 mmol). The reaction mixture was stirred under an N₂ atmosphere for 15 h at 150 °C, after which time, it was transferred to a separatory funnel and 100 mL of water were added. Concentrated HCl was then added in order to acidify the reaction mixture to pH<2. The aqueous layer was subsequently washed three times with 90 mL ethyl acetate. The ethyl acetate layers were then washed two times with 150 mL water, three times with 100 mL brine and then dried over sodium sulfate. The ethyl acetate was removed on a rotary-evaporator. A slurry was formed by adding ethyl acetate and dichloromethane to the dried crude product, filtration yielded N-(3-chloroquinoxalin-2-yl)-benzenesulfonamide which was used without further purification. MS (EI) m/z C₁₄H₁₀ClN₃O₂S: 319.9 (MH⁺).

[0354] A CEM microwave reaction vessel was charged with N-(3-chloroquinoxalin-2-yl)benzenesulfonamide (52 mg, 0.16 mmol), prepared using procedures similar to those described in the above step, 4-fluoroaniline (36 mg, 0.32 mmol), and 0.8 mL of dimethylacetamide. The vessel was sealed and the reaction mixture was heated under microwave radiation for 25 m at 120 °C in a CEM Discover microwave instrument. Methanol (1 mL) was added to the reaction mixture and after 20 minutes the product precipitated out of the solution. Filtration yielded N-(3-(4-fluorophenylamino)quinoxalin-2-yl)benzenesulfonamide (39 mg, 62 %). ¹H-NMR (400MHz, d₆-DMSO): δ 12.30 (s, 1H), 9.11 (s, 1H), 8.16-8.10 (d, 2H), 8.02-7.90 (m, 3H), 7.68-7.58 (m, 3H), 7.55-7.51 (m, 1H), 7.41-7.32 (m, 2H), 7.25-7.16 (m, 2H); MS (EI) m/z C₂₀H₁₅FN₄O₂S: 395.0 (MH⁺).

Example 374

N-(3-(N-(3-chloroquinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide

[0355] 

Scheme A

[0356] A flask was charged with 3-aminobenzene sulfonamide (3.3 g, 19 mmol), and 20 mL of 1:1 acetone:H₂O. The solution was stirred at room temperature until the aminobenzene sulfonamide had dissolved. The flask was then cooled in an ice bath and dimethylamino-acetyl chloride HCl (4.6 g, 29 mmol) was added. To the resulting slurry sodium bicarbonate (4.8 g, 57 mmol) was added over a 15 m period. After 30 min the reaction was removed from the ice bath and allowed to stir at room temperature for 15 h. The reaction mixture was then filtered and washed with methanol and acetonitrile. The filtrate was dried on a rotary evaporator to yield 2-(dimethylamino)-N-(3-sulfamoyl-phenyl)acetamide, which was submitted to the next step without further purification. MS (EI) m/z C₁₀H₁₅N₃O₃S: 258.0 (MH⁺).

Scheme B

[0357] A flask was charged with dichloroquinozaline (1.0 g, 5.8 mmol), 10 mL of dimethylacetamide, 2-(dimetyhlamino)-N-(3-sulfamoylphenyl)acetamide (0.70 g, 2.7 mmol), and cesium carbonate (1.8 g, 5.5 mmol). The reaction mixture was stirred for 3 h at 140 °C and then filtered. The solvent was evaporated from the filtrate on a rotary-evaporator to yield (N-(3-(N-(3-chloroquinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide) which was submitted to the next step without further purification. MS (EI) m/z C₁₈H₁₈ClN₅O₃S: 420.0 (MH⁺).

General Amination Procedure 1a

[0358] 

[0359] A CEM microwave reaction vessel was charged with N-(3-(N-(3-chloroquinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide (30 mg, 0.071 mmol), prepared using procedures similar to those described in Example 374, the desired aniline (16 mg, 0.14 mmol, 2 eq), and 0.5 mL of dimethylacetamide. The vessel was sealed and the reaction mixture was heated under microwave radiation for 70 min at 140 °C in a CEM Discover microwave instrument. The solvent was then removed by rotary-evaporation. Purification of the final product was accomplished by preparatory reverse-phase HPLC with the eluents 25 mM aqueous NH₄OAc/ACN to the desired product.

[0360] The following compounds were prepared according to the above General Amination Procedure 1a.
Example 375: 2-(dimethylamino)-N-(3-(N-(3-(3-fluorophenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. ¹H-NMR (400MHz, CDCl₃): 9.40 ppm (s, 1H), 8.43 ppm (s, 1H), 8.22 ppm (s, 1H), 8.07-8.02 ppm (d, 1H), 7.97-7.93 ppm (d, 1H), 7.76-7.71 (m, 2H), 7.53-7.48 ppm (t, 1H), 7.45-7.36 ppm (m, 4H), 7.35-7.28 ppm (m, 2H), 6.84-6.77 ppm (t, 1H), 3.10 ppm (s, 2H), 2.38 ppm (s, 6H); MS (EI) m/z C₂₄H₂₃FN₆O₃S: 495 (MH⁺).
Example 376: 2-(dimethylamino)-N-(3-(N-(3-(4-fluorophenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₂₄H₂₃FN₆O₃S: 495 (MH⁺).
Example 377: N-(3-(N-(3-(4-chloro-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide. MS (EI) m/z C₂₄H₂₃ClN₆O₃S: 511 (MH⁺).

General Amination Procedure 1b

[0361] 

[0362] A CEM microwave reaction vessel was charged with N-(3-(N-(3-chloroquinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide (62 mg, 0.147 mmol), prepared using procedures similar to those in Example 374, the desired aniline (0.567 mmol, 4 eq), and 1.0 mL of toluene. The vessel was sealed and the reaction mixture was heated under microwave radiation for 60 min at 180 °C in a CEM Discover microwave instrument. The solvent was removed on a rotary-evaporator. Purification of the final product was done by preparatory HPLC with NH₄OAc/ACN as eluent to yield the desired product.

[0363] The following compounds were prepared according to the above General Amination Procedure 1b.
Example 378N-(3-(N-(3-(3-chtoro-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-2-(dimethylamino)acetamide. MS (EI) m/z C₂₄H₂₃ClN₆O₃S: 511 (MH⁺).
Example 379: 2-(dimethylamino)-N-(3-(N-(3-(4-fluoro-3-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. 2-(dimethylamino)-N-(3-(N-(3-(4-fluoro-3-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)phenyl). ¹H-NMR (400MHz, CDCl₃): δ 9.47 (s, 1H), 8.36 (s, 1H), 8.29 (s, 1H), 7.91-7.87 (d, 1H), 7.80-7.73 (m, 2H), 7.66-7.63 (d, 1H), 7.53-7.47 (t, 1H), 7.43-7.30
(m, 4H), 7.10-7.04 (t, 1H), 6.55-5.95 (br s, 1H), 3.96 (s, 3H), 3.12 (s, 2H), 2.39 (s, 6H), 2.08 (s,3H(Ac0H); MS (EI) m/z C₂₅H₂₅FN₆O₄S: 525 (MH⁺).

Example 380

N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-isopropoxybenzenesulfonamide

[0364] 

[0365] N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-isopropoxy-benzenesulfonamide. A solution of 2,3-dichloroquinoxaline (2.0 mL, 0.38 M) was combined with K₂CO₃ (105 mg, 0.76 mmol) in a glass vial. A solution of 4-isopropoxybenzene sulfonamide (1.75 mL, 0.43 M) was added and the solution was stirred overnight at 125 °C. After cooling, acetic acid (45 mL, 0.79 mmol) and 3,5-dimethoxyaniline (230 mg, 1.5 mmol) were added. The reaction mixture was stirred again at 125 °C overnight. Upon cooling, the reaction mixture was diluted with 8 mL of methanol and then 8 mL of water. The precipitate was collected by filtration and recrystallized from N,N-dimethylacetamide/water to give N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-isopropoxy-benzenesulfonamide (45 mg, 12%). ¹H-NMR (400MHz, d₆-DMSO): 12.16 (bs, 1H), 8.93 (s, 1H), 8.03 (d, 2H), 7.92 (bs, 1H), 7.56 (d, 1H), 7.36 (m, 4H), 7.07 (d, 2H), 6.24 (s, 1H), 4.72 (m, 1H), 3.76 (s, 6H), 1.27 (d, 6H); MS (EI) m/z C₂₅H₂₆N₄0₅S: 495 (MH⁺).

[0366] Examples 381-411 were synthesized proceeding as above in Example 423. In the cases where the product did not precipitate, the mixture was purified by reverse phase HPLC.
Example 381: 3-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-methylbenzenesulfonamide. ¹H-NMR (400MHz, d₆-DMSO): 12.31 (bs, 1H), 8.96 (s, 1H), 8.18 (s, 1H), 7.98 (d, 1 H), 7.92 (bs, 1H), 7.58 (d, 2H), 7.43-7.33 (m, 4H), 6.24 (t, 1H), 3.76 (s, 6H), 2.39 (s, 3H); MS (EI) m/z C₂₃H₂₁ClN₄0₄S: 485 (MH⁺).
Example 382: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)naphthalene-1-sulfonamide. MS (EI) m/z C₂₆H₂₂N₄O₄S: 487 (MH⁺).
Example 383: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-fluorobenzenesulfonamide. MS (EI) m/z C₂₂H₁₉FN₄O₄S: 455 (MH⁺).
Example 384: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-fluorobenzenesulfonamide. MS (EI) m/z C₂₂H₁₉FN₄O₄S: 455 (MH⁺).
Example 385: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-(trifluoromethyl)benzenesulfonamide. MS (EI) m/z C₂₃H₁₉F₃N₄O₄S: 505 (MH⁺).
Example 386: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-(trifluoromethyl)benzenesulfonamide. MS (EI) m/z C₂₃H₁₉F₃N₄O₄S: 505 (MH⁺).
Example 387: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-(trifluoromethoxy)benzenesulfonamide. MS (EI) m/z C₂₃H₁₉F₃N₄O₅S: 521 (MH⁺).
Example 388: N-(4-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)acetamide. MS (EI) m/z C₂₄H₂₃N₅O₅S: 494 (MH⁺).
Example 389: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-fluoro-2-methylbenzenesulfonamide. MS (EI) m/z C₂₃H₂₁FN₄O₄S: 469 (MH⁺).
Example 390: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2-methylbenzenesulfonamide. MS (EI) m/z C₂₃H₂₂N₄O₄S: 451 (MH⁺).
Example 391: 2-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z C₂₂H₁₉ClN₄O₄S: 471 (MH⁺).
Example 392: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3,5-difluorobenzenesulfonamide. MS (EI) m/z C₂₂H₁₈F₂N₄O₄S: 473 (MH⁺).
Example 393: 3,5-dichloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z C₂₂H₁₈Cl₂N₄O₄S: 505 (MH⁺).
Example 394: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-fluoro-4-methylbenzenesulfonamide. MS (EI) m/z C₂₃H₂₁FN₄O₄S: 469 (MH⁺).
Example 395: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2-(trifluoromethyl)benzenesulfonamide. MS (EI) m/z C₂₃H₁₉F₃N₄O₄S: 505 (MH⁺).
Example 396: 4-cyano-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z C₂₃H₁₉N₅O₄S: 462 (MH⁺).
Example 397: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-1-phenylmethanesulfonamide. MS (EI) m/z C₂₃H₂₂N₄O₄S: 451 (MH⁺).
Example 398: 4,5-dichloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)thiophene-2-sulfonamide. MS (EI) m/z C₂₀H₁₆Cl₂N₄O₄S₂: 511 (MH⁺).
Example 399: 1-(3-chlorophenyl)-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)methanesulfonamide. MS (EI) m/z C₂₃H₂₁ClN₄O₄S: 485 (MH⁺).
Example 400: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2,5-dimethylthiophene-3-sulfonamide. MS (EI) m/z C₂₂H₂₂N₄O₄S₂: 471 (MH⁺).
Example 401: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3,5-bis(trifluoromethyl)benzenesulfonamide. MS (EI) m/z C₂₄H₁₈F₆N₄O₄S: 573 (MH⁺).
Example 402: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-fluoro-3-(trifluoromethyl)benzenesulfonamide. MS (EI) m/z C₂₃H₁₈F₄N₄O₄S: 523 (MH⁺).
Example 403: 5-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-1,3-dlmethyl-1H-pyrazole-4-sulfonamide. MS (EI) m/z C₂₁H₂₁ClN₆O₄S: 489 (MH⁺).
Example 404: 5-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2-methoxybenzenesulfonamide. MS (EI) m/z C₂₃H₂₁ClN₄O₅S: 501 (MH⁺).
Example 405: 5-bromo-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2-methoxybenzenesulfonamide. MS (EI) m/z C₂₃H₂₁BrN₄O₅S: 545 (MH⁺).
Example 406: 2,5-dichloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)thiophene-3-sulfonamide. MS (EI) m/z C₂₀H₁₆Cl₂N₄O₄S₂: 511 (MH⁺).
Example 407: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3,5-dimethylisoxazole-4-sulfonamide. MS (EI) m/z C₂₁H₂₁N₅O₅S: 456 (MH⁺).
Example 408: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-2,5-dimethoxybenzenesulfonamide. MS (EI) m/z C₂₄H₂₄N₄O₆S: 497 (MH⁺).
Example 409: 3-chloro-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-4-fluorobenzenesulfonamide. MS (EI) m/z C₂₂H₁₈ClFN₄O₄S: 489 (MH⁺).
Example 410: 4-(difluoromethoxy)-N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide MS (EI) m/z C₂₃H₂₀F₂N₄O₅S: 503 (MH⁺).
Example 411: N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-3-(methylsulfonyl)benzenesulfonamide. MS (EI) m/z C₂₃H₂₂N₄O₆S₂: 515 (MH⁺).

General Acylation Procedure 2

[0367] 

[0368] N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)-sulfamoyl)phenyl)azetidine-3-carboxamide (125 mg, 0.23 mmol), prepared using procedures similar to those described in Example 372, was dissolved into 5 mL DCE in a 10 mL round-bottom flask. DIEA (1.17 mmol, 5.0 equiv.) was then added with stirring followed by acid chloride (0.47 mmol, 2.0 equiv.). The reaction was then stirred at room temperature for 1 hour or until complete as indicated by LCMS. The solvent was subsequently removed under reduced pressure on a rotary evaporator. The crude material was then redissolved in methanol. Purification of the final product was accomplished by preparatory reverse-phase HPLC with the eluents 25 mM aqueous NH₄OAc/CAN. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C 18, OCD 5 µM, 30 X 70 mm column and running a 5-100 % gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification.

[0369] The following compounds were prepared according to General Acylation Procedure 2.
Example 412: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-propionylazetidine-3-carboxamide. ¹H-NMR (400MHz, d₆-DMSO): 12.40 (s, I H), 10.45 (s, 1H), 8.88 (s, 1H), 8.40 (s, 1H), 7.93 (s, 1H), 7.82 (d, 1H), 7.77 (d, 1H), 7.60-7.45 (m, 2H), 7.41-7.30 (m, 4H), 6.24 (s, 1H), 4.26 (t, 1H), 4.22-4.17 (m, 1H), 3.99 (t, 1H), 3.95-3.89 (m, 1H), 3.76 (s, 6H), 3.59-3.45 (m, 1H), 2.05 (dd, 2H), 0.95 (t, 3H); MS (EI) m/z C₂₉H₃₀N₆O₆S: 591 (MH⁺).
Example 413: 1-acetyl-N-(3-{[(3-{[3,5-bis(methoxy)-phenyl]amino}quinoxalin-2-yl)amino]sulfonyl}phenyl)azetidine-3-carboxamide. MS (EI) m/z C₂₈H₂₈N₆O₆S: 577 (MH⁺).
Example 414: 1-(cyclopropanecarbonyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide. MS (EI) m/z C₃₀H₃₀N₆O₆S: 603 (MH⁺).

General Reductive Amination Procedure 1

[0370] 

[0371] To a solution of N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide (110 mg, 0.19 mmol), prepared using procedures similar to those described in Example 372, in 3 mL of DCE and 200 µL of DMF, aldehyde (0.77 mmol, 4.0 eq.)was added slowly followed by tetramethylammonium triacetoxyborohydride (1.16 mmol, 6.0 eq). The reaction was stirred at room temperature overnight. LC/MS indicated the reaction was completed. The solvent was subsequently removed under reduced pressure on a rotary evaporator. The crude material was then redissolved in methanol. Purification of the final product was accomplished by preparatory reverse-phase HPLC with the eluents 25 mM aqueous NH₄OAc/CAN. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C18, OCD 5 µM, 30 X 70 mm column and running a 5-100 % gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification.

[0372] The following title compounds were prepared according to General Reductive Amination Procedure 1.
Example 415: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-ethylazetidine-3-carboxamide. ¹H-NMR (400MHz, d₆-DMSO): 10.29 (s, 1H), 8.82 (s, 1H), 8.25 (t, 1H), 7.75-7.68 (m, 2H), 7.43-7.38 (m, 1H), 7.375-7.340 (m, 1H), 7.338-7.310 (d, 2H), 7.305-7.262 (m, 1H), 7.15-7.08 (m, 2H), 6.56 (s, 1H), 6.15 (t, 1H), 4.15-4.08 (m, 2H), 4.06-3.95 (m, 2H), 3.78 (s, 6H), 3.65-3.56 (m, 1H), 3.12-3.04 (m, 2H), 1.03 (t, 3H); MS (EI) m/z C₂₈H₃₀N₆O₅S: 563 (MH⁺).
Example 416: 1-(cyclopropylmethyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide. MS (EI) m/z C₃₀H₃₂N₆O₅S: 589 (MH⁺).
Example 417: 1-benzyl-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide. MS (EI) m/z C₃₃H₃₂N₆O₅S: 625 (MH⁺).
Example 418: N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)-1-(furan-2-ylmethyl)azetidine-3-carboxamide. MS (EI) m/z C₃₁H₃₀N₆O₆S: 615 (MH⁺).
Example 419: 1-((1H-imidazol-5-yl)methyl)-N-(3-(N-(3-(3,5-dimethoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)phenyl)azetidine-3-carboxamide. MS (EI) m/z C₃₀H₃₀N₈O₅S: 615 (MH⁺).

General Amide Formation Procedure 1a

[0373] 

[0374] Into a small 1 dram vial was added 3-(N-(3-(2-chloro-5-methoxy-phenylamino)-quinoxalin-2-yl)sulfamoyl)benzoic acid (61 mg, 0.13 mmol, 1.1 equiv), prepared using procedures described for Example 100. The acid was dissolved in DMA (1 mL) and DIEA (42 µL, 0.24 mmol, 2 equiv) was added then added to the solution. The amine reagent (1 mL of 0.12 M solution in DMA) was added to solution with stirring followed by HATU (64 mg, 0.17 mMol, 1.4 equiv). The reaction was stirred overnight at room temperature. Upon completion as indicated by LCMS analysis, 2 mL of methanol was added to the solution. Preparative reverse-phase HPLC was used to isolate the desired product. A Waters Fractionlynx preparative reverse-phase HPLC - equipped with a Waters SunFire Prep C18, OCD 5 µM, 30 X 70 mm column and running a 5-100 % gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile - was used to carry out the purification.

[0375] The following compounds were prepared according to General Amide Formation Procedure 1.
Example 420: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-(dimethylamino)propyl)benzamide. 3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-(dimethylamino)propyl)benzamide: ¹H NMR (400 MHz, d₆-DMSO): 9.44 (s, 1H), 8.94 (s, 1H), 8.79 (t, 1H), 8.54 (s, 1H), 8.24 (d, 1H), 7.87 (d, 1H), 7.48 (m, 3H), 7.33 (d, 1H), 7.18 (m, 2H), 6.60 (dd, 1H), 3.82 (1H), 3.04 (m, 3H), 2.51 (m, 5H), 1.91 (s, 1H), 1.86 (m, 3H); MS (EI) m/z for C₂₇H₂₉ClN₆O₄S: 569 (MH⁺).
Example 421: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(1-methylazetidin-3-yl)benzamide. 3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(1-methylazetidin-3-yl)benzamide: ¹H NMR (400 MHz, d₆-DMSO): 9.43 (s, 1H), 9.23 (d, 1H), 8.94 (d, 1H), 8.58 (s, 1H), 8.29 (d, 1H), 7.89 (d, 1H), 7.56 (t, 1H), 7.47 (d, 1H), 7.44 (d, 1H), 7.33 (d, 1H), 7.18 (m, 2H), 6.60 (dd, 1H), 4.81 (m, 1H), 4.33 (m, 2H), 4.19 (m, 2H), 3.82 (s, 1H), 2.51 (s, 3H); MS (EI) m/z for C₂₆H₂₅ClN₆O₄S: 553 (MH⁺).
Example 422: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(pyridin-4-ylmethyl)benzamide. MS (EI) m/z C₂₈H₂₃ClN₆O₄S: 575 (MH⁺).
Example 423: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-(dimethylamino)propyl)benzamide. MS (EI) m/z C₂₈H₂₆ClN₇O₄S: 592 (MH⁺).
Example 424: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(2,2-dimethylhydrazinecarbonyl)benzenesulfonamide. MS (EI) m/z C₂₄H₂₃ClN₆O₄S: 527 (MH⁺).
Example 425: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-methoxyethyl)benzamide. MS (EI) m/z C₂₅H₂₄ClN₅O₅S: 542 (MH⁺).
Example 426: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(4-methylpiperazine-1-carbonyl)benzenesulfonamide. MS (EI) m/z C₂₇H₂₇ClN₆O₄S: 567 (MH⁺).
Example 427: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(pyrrolidin-1-yl)ethyl)benzamide. MS (EI) m/z C₂₈H₂₉ClN₆O₄S: 581 (MH⁺).
Example 428: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(pyridin-4-yl)ethyl)benzamide. MS (EI) m/z C₂₉H₂₅ClN₆O₄S: 589 (MH⁺).
Example 429: N-(2-(1H-imidazol-4-yl)ethyl)-3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)benzamide. MS (EI) m/z C₂₇H₂₄ClN₇O₄S: 578 (MH⁺).
Example 430: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(piperidin-1-yl)benzamide. MS (EI) m/z C₂₇H₂₇ClN₆O₄S: 567 (MH⁺).
Example 431: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-hydroxyethyl)benzamide. MS (EI) m/z C₂₄H₂₂ClN₅O₅S: 528 (MH⁺).
Example 432: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-ethoxypropyl)benzamide. MS (EI) m/z C₂₇H₂₈ClN₅O₅S: 570 (MH⁺).
Example 433: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-(pyrrolidin-1-yl)propyl)benzamide. MS (EI) m/z C₂₉H₃₁ClN₆O₄S: 595 (MH⁺).
Example 434: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-(diethylamino)propyl)benzamide. MS (EI) m/z C₂₉H₃₃ClN₆O₄S: 597 (MH⁺).
Example 435: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-(2-oxopyrrolidin-1-yl)propyl)benzamide. MS (EI) m/z C₂₉H₂₉ClN₆O₅S: 609 (MH⁺).
Example 436: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(pyridin-2-ylmethyl)benzamide. MS (EI) m/z C₂₈H₂₃ClN₆O₄S: 575 (MH⁺).
Example 437: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-cyanoethyl)-N-methylbenzamide. MS (EI) m/z C₂₆H₂₃ClN₆O₄S: 551 (MH⁺).
Example 438: 3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-cyanoethyl)-N-ethylbenzamide. MS (EI) m/z C₁₇H₂₅ClN₆O₄S: 565 (MH⁺).
Example 439: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(ethylthio)ethyl)benzamide. MS (EI) m/z C₂₆H₂₆ClN₅O₄S₂: 572 (MH⁺).
Example 440: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-propoxypropyl)benzamide. MS (EI) m/z C₂₈H₃₀ClN₅O₅S: 584 (MH⁺).
Example 441: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(5-(diethylamino)pentan-2-yl)benzamide. MS (EI) m/z C₃₁H₃₇ClN₆O₄S: 625 (MH⁺).
Example 442: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-methoxypropyl)benzamide. MS (EI) m/z C₂₆H₂₆ClN₅O₅S: 556 (MH⁺).
Example 443: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-morpholinopropyl)benzamide MS (EI) m/z C₂₉H₃₁ClN₆O₅S: 611 (MH⁺).
Example 444: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(pyridin-3-ylmethyl)benzamide MS (EI) m/z C₂₈H₂₃ClN₆O₄S: 575 (MH⁺).
Example 445: 3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-cyanoethyl)benzamide. MS (EI) m/z C₂₅H₂₁ClN₆O₄S: 537 (MH⁺). Example 446: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(1-methoxypropan-2-yl)benzamide. MS (EI) m/z C₂₆H₂₆ClN₅O₅S: 556 (MH⁺).
Example 447: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(methylthio)ethyl)benzamide. MS (EI) m/z C₂₅H₂₄ClN₅O₄S₂: 558 (MH⁺).
Example 448: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-(dimethylamino)propyl)-N-methylbenzamide. MS (EI) m/z C₂₈H₃₁ClN₆O₄S: 583 (MH⁺).
Example 449: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-isopropoxypropyl)benzamide. MS (EI) m/z C₂₈H₃₀ClN₅O₅S: 584 (MH⁺).
Example 450: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(dimethylamino)ethyl)-N-ethylbenzamide. MS (EI) m/z C₂₈H₃₁ClN₆O₄S: 583 (MH⁺).
Example 451: N-(3-butoxypropyl)-3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)benzamide. MS (EI) m/z C₂₉H₃₂ClN₅O₅S: 598 (MH⁺).
Example 452: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(diethylamino)ethyl)benzamide. MS (EI) m/z C₂₈H₃₁ClN₆O₄S: 583 (MH⁺).
Example 453: methyl 3-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)benzamido)propanoate. MS (EI) m/z C₂₆H₂₄ClN₅O₆S: 570 (MH⁺).
Example 454: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-methyl-N-propylbenzamide. MS (EI) m/z C₂₆H₂₆ClN₅O₄S: 540 (MH⁺).
Example 455: ethyl 3-(3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)benzamido)propanoate. MS (EI) m/z C₂₇H₂₆ClN₅O₆S: 584 (MH⁺).
Example 456: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-(piperidin-1-yl)ethyl)benzamide. MS (EI) m/z C₂₉H₃₁ClN₆O₄S: 595 (MH⁺).
Example 457: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-((1-ethylpyrrolidin-2-yl)methyl)benzamide. MS (EI) m/z C₂₉H₃₁ClN₆O₄S: 595 (MH⁺).
Example 458: N-(2-(bis(2-hydroxyethyl)amino)ethyl)-3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)benzamide. MS (EI) m/z C₂₈H₃₁ClN₆O₆S: 615 (MH⁺).
Example 459: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(3-(diethylamino)pyrrolidine-1-carbonyl)benzenesulfonamide. MS (EI) m/z C₃₀H₃₃ClN₆O₄S: 609 (MH⁺).
Example 460: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-methyl-N-(1-methylpyrrolidin-3-yl)benzamide. MS (EI) m/z C₂₈H₂₉ClN₆O₄S: 581 (MH⁺).
Example 461: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(3-(dimethylamino)pyrrolidine-1-carbonyl)benzenesulfonamide. MS (EI) m/z C₂₈H₂₉ClN₆O₄S: 581 (MH⁺).
Example 462: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(2-methyl-1-morpholinopropan-2-yl)benzamide. MS (EI) m/z C₃₀H₃₃ClN₆O₅S: 625 (MH⁺).
Example 463: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(1H-pyrrol-1-yl)benzamide. MS (EI) m/z C₂₆H₂₁ClN₆O₄S: 549 (MH⁺).
Example 464: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(3-oxopyrazolidin-4-yl)benzamide. MS (EI) m/z C₂₅H₂₂ClN₇O₅S: 568 (MH⁺).
Example 465: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(2-((dimethylamino)methyl)plperidine-1-carbonyl)benzenesulfonamide. MS (EI) m/z C₃₀H₃₃ClN₆O₄S: 609 (MH⁺).
Example 466: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(2-(piperidin-1-ylmethyl)piperidine-1-carbonyl)benzenesulfonamide. MS (EI) m/z C₃₃H₃₇ClN₆O₄S: 649 (MH⁺).
Example 467: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(1-ethylpiperidin-3-yl)benzamide MS (EI) m/z C₂₉H₃₁ClN₆O₄S: 595 (MH⁺).

General Amide Formation Procedure 1b

[0376] The procedure outlined in General Amide Formation Procedure 1a was used to incorporate a number of amines that contained a second amine group protected as the tert-butylcarbamate (i.e. where R', within NHR'R", contained a Boc-protected amine group). The deprotection was carried out after HPLC purification of the Boc-protected precursor.

[0377] Into a small 1 dram vial was added 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)benzoic acid (61 mg, 0.13 mmol, 1.1 equiv). The acid was dissolved in 1 mL of DMA and DIEA (42 µL, 0.24 mmol, 2 equiv) was added then added to the solution. The mono-Boc-protected diamine reagent (1 mL of 0.12 M solution in DMA, 1 equiv) was added to solution with stirring followed by HATU (64 mg, 0.17 mmol, 1.4 equiv). The reaction was stirred overnight at room temperature. Upon completion as indicated by LCMS analysis, 2 mL of methanol was added to the solution. Preparative reverse-phase HPLC was used to isolate the desired product directly from this crude reaction solution. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C 18, OCD 5 µM, 30 X 70 mm column and running a 5-100 % gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification. The product fractions were combined and concentrated to dryness under reduced pressure by rotary evaporation. A solution of 4 N HCl in dioxane (2 mL) was added. The solution was then stirred at room temperature until no starting material was detected. The deprotected product precipitated out of solution as an HCL salt and was collected by filtration, washed with ether and dried under vacuum.

[0378] The following compounds were prepared according to the above General Amide Formation Procedure 1b.
Example 468: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(piperidin-3-yl)benzamide. 3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(piperidin-3-yl)benzamide: ¹H NMR (400 MHz, d₆-DMSO): 12.82 (s, 1H), 9.12 (s, 1H), 9.04 (s, 1H), 8.85 (d, 1H), 8.65 (s, 1H), 8.55 (s, 1H), 8.18 (m, 1H), 7.98 (s, 1H), 7.69 (m, 2H), 7.43 (m, 2H), 6.69 (dd, 1H), 4.21 (s, 1H), 3.83 (s, 3H), 3.69 (m, 1H), 3.48 (m, 1H), 3.18 (s, 1H), 2.84 (q, 2H), 1.91 (s, 2H); MS (EI) m/z for C₂₇H₂₇ClN₆O₄S: 567 (MH⁺).
Example 469: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(piperidin-2-ylmethyl)benzamide. 3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(piperidin-2-ylmethyl)benzamide: NMR (400 MHz, d₆-DMSO): 12.78 (s, 1H), 9.16 (s, 1H), 9.09 (s, 1H), 8.79 (s, 1H), 8.59 (d, 2H), 8.22 (t, 2H), 7.99 (s, 1H), 7.74 (t, 1H), 7.66 (s, 1H), 7.42 (m, 2H), 6.69 (dd, 1H), 3.82 (s, 3H), 3.69 (dd, 1H), 3.57 (m, 1H), 3.50 (m, 3H), 3.22 (s, 2H), 2.82 (d, 1H), 1.68 (m, 5H); MS (EI) m/z for C₂₈H₂₉ClN₆O₄S: 581 (MH⁺).
Example 470: 3-(3-aminopyrrolidine-1-carbonyl)-N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z C₂₆H₂₅ClN₆O₄S: 553 (MH⁺).
Example 471: 3-(3-aminoazetidine-1-carbonyl)-N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z C₂₅H₂₃ClN₆O₄S: 539 (MH⁺).
Example 472: 3-(3-aminopiperidine-1-carbonyl)-N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z C₂₇H₂₇ClN₆O₄S: 567 (MH⁺).
Example 473: 3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)-N-(pyrrolidin-3-yl)benzamide. MS (EI) m/z C₂₆H₂₅ClN₆O₄S: 553 (MH⁺).
Example 474: N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)-3-(3-(methylamino)pyrrolidine-1-carbonyl)benzenesulfonamide. MS (EI) m/z C₂₇H₂₇ClN₆O₄S: 567 (MH⁺).
Example 475: N-(2-aminoethyl)-3-(N-(3-(2-chloro-5-methoxy-phenylamino)quinoxalin-2-yl)sulfamoyl)benzamide. MS (EI) m/z C₂₄H₂₃ClN₆O₄S: 527 (MH⁺).
Example 476: 3-(4-amino-3-oxopyrazolidine-1-carbonyl)-N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)benzenesulfonamide. MS (EI) m/z C₂₅H₂₂ClN₇O₅S: 568 (MH⁺).

Example 477

3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-((1-methylpiperidin-2-yl)methyl)benzamide

[0379] 3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(piperidin-2-ylmethyl)benzamide (299 mg, 0.51 mmol, 1 equiv), prepared using procedures similar to those described for Example 514, was dissolved in 2.3 mL of DMA. Formic acid (388 µL, 10.28 mmol, 20 equiv) was added to solution with stirring followed by the addition of formaldehyde (508 µL of 37% aq. solution). The reaction was then stirred at room temperature overnight. Analysis of an aliquot of the reaction mixture by LCMS indicated the complete consumption of starting material. The reaction was diluted with methanol (2 mL). Preparative reverse-phase HPLC was used to isolate the desired product directly from the crude reaction mixture. A Waters Fractionlynx preparative reverse-phase HPLC; equipped with a Waters SunFire Prep C 18, OCD 5 µM, 30 X 70 mm column and running a 5-100 % gradient with a binary solvent system of 25 mM ammonium acetate in water/acetonitrile; was used to carry out the purification. ¹H NMR (400 MHz, d₆-DMSO): 9.44 (s, 1H), 8.94 (s, 1H), 8.79 (t, I H), 8.57 (s, 1H), 8.27 (d, 1H), 7.90 (d, 1H) 7.54 (t, 1H), 7.46 (d, 1H), 7.39 (d, 1H), 7.33 (d, 1H), 7.18 (m, 2H), 6.60 (dd, 1H), 3.82 (s, 3H), 3.59 (m, 2H), 3.00 (s, 1H), 2.90 (s, 3H), 1.62 (m, 7H); MS (EI) m/z for C₂₉H₃₁ClN₆O₄S: 595 (MH⁺).

Example 478

3-(N-(3-(2-chloro-5-methoxyphenylamino)quinoxalin-2-yl)sulfamoyl)-N-(1-methylpiperidin-3-yl)benzamide

[0380] The title compound was prepared using similar procedures to those used in Example 522. ¹H NMR (400 MHz, d₆-DMSO): 9.43 (s, 1H), 8.93 (s, 1H), 8.59 (s, 1H), 8.24 (d, 1H), 7.87 (d, I H), 7.47 (m, 2H), 7.40 (d, 1H), 7.33 (d, 1H), 7.19 (m, 2H), 6.60 (dd, 1H), 4.21 (s, 1H), 3.82 (s, I H), 2.76 (s, 1H), 2.50 (m, 7H), 1.91 (m, 2H), 1.63 (m, 2H); MS (EI) m/z for C₂₈H₂₉ClN₆O₄S: 581 (MH⁺).

Biological Examples

Biological Example 1

PI3Kalpha Luciferase-Coupled Chemiluminescence Assay Protocol

[0381] PI3Kα activity is measured as the percent of ATP consumed following the kinase reaction using luciferase-luciferin-coupled chemiluminescence. Reactions were conducted in 384-well white, medium binding microtiter plates (Greiner). Kinase reactions were initiated by combining test compounds, ATP, substrate (PIP2), and kinase in a 20 µL volume in a buffer solution. The standard PI3Kalpha assay buffer is composed 50 mM Tris, pH 7.5, 1 mM EGTA, 10 mM MgCl₂, 1 mM DTT and 0.03% CHAPS. The standard assay concentrations for enzyme, ATP, and substrate are 0.5-1.1 nM, 1µM, and 7.5 µM, respectively. The reaction mixture was incubated at ambient temperature for approximately 2 h. Following the kinase reaction, a 10 µL aliquot of luciferase-luciferin mix (Promega Kinase-Glo) was added and the chemiluminescence signal measured using a Victor2 plate reader (Perkin Elmer). Total ATP consumption was limited to 40-60% and IC50 values of control compounds correlate well with literature references.

[0382] Certain compounds of Formula (I) demonstrated the ability to bind to PI3K when tested in this assay. The following embodiments are directed to the compounds themselves as well as their use in a method of treating. For example, in one option, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 8 µM or less. In another option, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 4 µM or less. In another option, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 3 µM or less. In another option, the PI3K inhibitor is selected from the compounds in Table I having a PI3K-binding affinity of about 2 µM or less. In another option, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 1.5 µM or less. In another embodiment, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 1 µM or less. In another option, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 0.750 µM or less. In another option, the PI3K inhibitor is selected from the compounds in Table I having a PI3K-binding affinity of about 0.5 µM or less. In another option, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 0.3 µM or less. In another option, the PI3K inhibitor is selected from the compounds in Table I having a PI3K-binding affinity of about 0.2 µM or less. In another option, the PI3K inhibitor is selected from the compounds in Table I having a PI3K-binding affinity of about 0.1 µM or
less. In another option, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 0.075 µM or less. In another option, the PI3K inhibitor is selected from the compounds in Table 1 having a PI3K-binding affinity of about 0.050 µM or less.

Biological Example 2

Phospho AKT assay

[0383] PC-3 cells were seeded on 6-well plates at 150,000 cells/well. Cells were cultured for 3 days, then treated with compounds in serum-free medium for 3 hr. EGF (100 ng/ml) was added for the last 10 min. Cells were lysed in TENN buffer. Phospho T308 Akt and total Akt were quantfied by ELISA performed according to the Biosource assay protocol. The readings of phospho Akt were normalized to total Akt readings.

Biological Example 3

Phospho S6 assay

[0384] PC-3 cells were seeded on 96-well plates at 8,000 cells/well. For each experiment, cells were seeded and treated in duplicated plates: one plate for phospho S6 CellELISA, and one plate for total S6 CellELISA. Cells were cultured on the plates for 3 days, then treated with compounds in serum-free medium for 3 hr in triplicate. Cells were fixed with 4% formaldehyde, quenched with 0.6% H2O2, blocked with 5% BSA, incubated with either phospho S6 antibody or total S6 antibody overnight, incubated with goat-anti-rabbit-IgG-HRP for I hr, and developed in chemiluminescent substrate.

Biological Example 4

PIP₃ assay

[0385] MCF-7 cells grown in 10-cm dishes were starved for 3 hours in DMEM, and then treated with compounds for 20 minutes. In the last 2 minutes of the incubation with the compounds, EGF (100 ng/ml) was added to stimulate the production of PIP3. The medium was aspirated and the cells were scraped with 10% trichloroacetic acid. The lipids were extracted from the pellet after the cell lysates were centrifuged. PIP3 in the cellular lipid extraction was quantified with the AlphaScreen [Registered TM of PerkinElmer] assay in which Grp1-PH is used as the PIP3 specific probe. The amount of cellular PIP3 was calculated from the standard curve of diC₈ PI (3,4,5) P3.

Biological Example 5-10

In vivo models

[0386] Compound A is a Compound of Formula 1. Compound B is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine.

[0387] Female and male athymic nude mice (NCr) 5-8 weeks of age and weighing approximately 20-25 g were used in the following model. Prior to initiation of a study, the animals were allowed to acclimate for a minimum of 48 h. During these studies, animals were provided food and water ad libitum and housed in a room conditioned at 70-75°F and 60% relative humidity. A 12 h light and 12 h dark cycle was maintained with automatic timers. All animals were examined daily for compound-induced or tumor-related deaths.

[0388] PC-3 human prostate adenocarcinoma cells were cultured in vitro in DMEM (Mediatech) supplemented with 20% Fetal Bovine Serum (Hyclone), Penicillin-Streptomycin and non-essential amino acids at 37 °C in a humidified 5% CO₂ atmosphere. On day 0, cells were harvested by trypsinization and 3x10⁶ cells (passage 13, 99% viability) in 0.1 mL of ice-cold Hank's balanced salt solution were implanted subcutaneously into the hindflank of 5-8 week old male nude mice. A transponder was implanted in each mouse for identification, and animals were monitored daily for clinical symptoms and survival. Body weights were recorded daily. Experiments were conducted with Compound A as a single agent as well as Compound A in combination with Taxol and Compound A in combination with Rapamycin. This model can be used to assess the desirability of treating with Compound A in combination with other anti-cancer agents.

[0389] U-87 MG human glioblastoma cells were cultured in vitro in DMEM (Mediatech) supplemented with 10% Fetal Bovine Serum (Hyclone), Penicillin-Streptomycin and non-essential amino acids at 37°C in a humidified 5% CO₂ atmosphere. On day 0, cells were harvested by trypsinization and 2x10⁶ cells (passage 5, 96% viability) in 0.1 mL of ice-cold Hank's balanced salt solution were implanted intradermally into the hindflank of 5-8 week old female nude mice. A transponder was implanted in each mouse for identification, and animals were monitored daily for clinical symptoms and survival. Body weights were recorded daily. Experiments were conducted with Compound A as a single agent and the results are not included. This model can be used to assess the desirability of treating with Compound A in combination with other anti-cancer agents.

[0390] A549 human lung carcinoma cells were cultured in vitro in DMEM (Mediatech) supplemented with 10% Fetal Bovine Serum (Hyclone), Penicillin-Streptomycin and non-essential amino acids at 37°C in a humidified 5% CO₂ atmosphere. On day 0, cells were harvested by trypsinization and 10x10⁶ cells (passage 12, 99% viability) in 0.1 mL of ice-cold Hank's balanced salt solution were implanted intradermally into the hindflank of 5-8 week old female nude mice. A transponder was implanted in each mouse for identification, and animals were monitored daily for clinical symptoms and survival. Body weights were recorded daily. Experiments were conducted with Compound A as a single agent as well as Compound A in combination with Compound B. This model can be used to assess the desirability of treating with Compound A in combination with other anti-cancer agents.

[0391] MDA-MB-468 human breast adenocarcinoma cells, passage number <6, were maintained and propagated in log-phase growth in Dulbecco's Modification of Eagles's Medium (DMEM; Mediatech) containing L-Glutamine supplemented with 10% Fetal Bovine Serum (Hyclone), Penicillin-Streptomycin and non-essential amino acids at 37 °C in a humidified, 5% CO₂ atmosphere. On day 0, cells were harvested by trypsinization, and 10 x 10⁶ cells (passage 10, 98% viability) in 50% cold Hanks balanced salt solution/50% Matrigel (100 µL total volume per mouse) were implanted subcutaneously into the mammary fat pads of female nude mice. Experiments were conducted with Compound A as a single agent as well as Compound A in combination with erlotinib. This model can be used to assess the desirability of treating with Compound A in combination with other anti-cancer agents.

[0392] Calu-6 human lung anaplastic carcinoma cells were cultured in vitro in DMEM (Mediatech) supplemented with 10% Fetal Bovine Serum (Hyclone), Penicillin-Streptomycin and non-essential amino acids at 37 °C in a humidified, 5% CO₂ atmosphere. On day 0, cells were harvested by trypsinization, and 5x10⁶ cells (passage #8, 96% viability) in 0.1 mL ice-cold Hank's balanced salt solution were implanted intradermally in the hind-flank of 5-8 week old female athymic nude mice. A transponder was implanted in each mouse for identification, and animals were monitored daily for clinical symptoms and survival. Body weights were recorded daily. Experiments were conducted with Compound A as a single agent as well as Compound A in combination with carboplatin. This model can be used to assess the desirability of treating with Compound A in combination with other anti-cancer agents.

[0393] MCF7 human mammary adenocarcinoma cells were cultured in vitro in DMEM (Cellgro) supplemented with 10% Fetal Bovine Serum (Cellgro), Penicillin-Streptomycin and non-essential amino acids at 37 °C in a humidified 5% CO₂ atmosphere. On day 0, cells were harvested by trypsinization, and 5 x 10⁶ cells (passage 10 and 95.4% viability for Study 1, passage 9 and 90% viability for Study 2) in 100 µL of a solution made of 50% cold Hanks balanced salt solution with 50% growth factor reduced matrigel (R&D Systems for Study I and Becton Dickinson for Study 2) implanted subcutaneously into the hindflank of female nude mice.

[0394] For subcutaneous or intradermal tumors, the mean tumor weight of each animal in the respective control and treatment groups was determined twice weekly during the study. Tumor weight (TW) was determined by measuring perpendicular diameters with a caliper, using the following formula:


These data were recorded and plotted on a tumor weight vs. days post-implantation line graph and presented graphically as an indication of tumor growth rates. Percent inhibition of tumor growth (TGI) is determined with the following formula:


where X₀ = average TW of all tumors on group day
X_f = TW of treated group on Day f
Y_f = TW of vehicle control group on Day f

[0395] If tumors regress below their starting sizes, then the percent tumor regression is determined with the following formula:

[0396] Tumor size is calculated individually for each tumor to obtain a mean ± SEM value for each experimental group. Statistical significance is determined using the 2-tailed Student's t-test (significance defined as P<0.05).

Biological Examples 11-14

[0397] Compound A is a Compound of Formula I and is an inhibitor of class I PI3-kinases. Compound B is N-(3,4-dichloro-2-fluorophenyl)-7-({[(3aR,5r,6aS)-2-methyloctahydrocyclopenta-[c]pyrrol-5-yl]methyl}oxy)-6-(methyloxy)quinazolin-4-amine.

Prostate Cancer Xenograft Model - A Compound of Formula I in Combination with Taxol

[0398] Compound A was tested alone and in combination with taxol in a prostate carcinoma tumor model. PC-3 is a human prostate carcinoma cell line that harbors a homozygous deletion mutation in PTEN, which results in constitutive activation of the PI3K pathway. In single-dose pharmacodynamic experiments, oral administration of Compound A results in a dose-dependent decrease in the phosphorylation of AKT, p70S6K, and S6 in PC-3 tumors grown ectopically in mice. Repeat-dose administration of a Compound A also inhibits the growth of these tumors, but does not induce regressions.

[0399] Oral administration of Compound A at 100mg/kg qd or 300 mg/kg biweekly (biw) resulted in substantial tumor growth inhibition in mice. See Figure 1. Comparable tumor growth inhibition was achieved with 7.5 mg/kg taxol administered i.v. twice weekly. While tumor growth was inhibited substantially with Compound A alone, the combination of either dose ofCompound A with taxol was superior to either agent alone and induced significant regression of the tumors. Body weight loss and dose skipping was minimal in all groups, and was not exacerbated in the combination group indicating that the combination was well tolerated. These results support the use of a Compound of Formula I in combination with taxol in tumors with constitutively activated PI3K signaling.

Prostate Cancer Xenograft Model - A Compound of Formula I in Combination with Rapamycin

[0400] Compound A was tested alone and in combination with rapamycin in a prostate carcinoma tumor model (PC-3 cell line). Oral administration of Compound A at 100mg/kg qd resulted in substantial tumor growth inhibition. See Figure 2. Comparable tumor growth inhibition was achieved with 5 mg/kg rapamycin administered i.p. daily. While tumor growth was inhibited substantially with Compound A alone, the combination of Compound A with rapamycin was superior to either agent alone and induced significant regression of the tumors. Body weight loss and dose skipping was minimal with each agent alone, but body weight loss was exacerbated in the combination group necessitating dose skipping. The fact that tumor regression was observed despite dose skipping suggests that using an intermittent dosing schedule would maintain efficacy and improve tolerability. These results support the use of a Compound of Formula I in combination with rapamycin in tumors with constitutively activated PI3K signaling.

Non-Small Cell Lung Cancer Xenograft Model - A Compound of Formula I in Combination with Carboplatin

[0401] Compound A was tested both as a single agent and in combination with carboplatin in a NSCLC tumor model.

[0402] Calu-6 is a human NSCLC cell line that harbors a heterozygous activating mutation in K-Ras (Q61K). Oral administration of a Compound A at 100mg/kg qd or 300 mg/kg every fourth day (q4d) to mice bearing Calu-6 tumors resulted in substantial tumor growth inhibition. See Figure 3. Both dose schedules resulted in similar inhibition of tumor growth. Significant tumor growth inhibition was also observed with 50 mg/kg carboplatin administered i.v. q4d, but was not as pronounced as with Compound A. While tumor growth was inhibited substantially with Compound A alone, the combination of the two agents was superior to either agent alone and resulted in almost complete inhibition of tumor growth. Body weight loss and dose skipping was minimal in all groups, and was not exacerbated in the combination group indicating that the combination was well tolerated. These results support the use of a Compound of Formula I both as a single agent and in combination with platins in tumors with activating mutations in K-Ras.

Non-small Cell Lung Cancer Xenograft - Model A Compound of Formula I in Combination with Compound B - Reference example

[0403] Compound A was tested both as a single agent and in combination with Compound B. The A549 human non-small cell lung carcinoma cell line harbors a homozygous stop mutation in the gene encoding LKB1, and an activating G12S mutation in K-Ras, promoting activation of both PI3K and mTOR. A549 cells also express wild-type EGFR.

[0404] As a single agent, Compound B, an inhibitor of EGFR, was orally administered once-daily at 30 mg/kg and Compound A was orally administered either at 30 mg/kg qd or 100 mg/kg q2d. Combination therapies consisted of Compound B with Compound A at 30 mg/kg or 100 mg/kg. Administration of each agent in the combination groups was separated by 6 h. Single agent administration of Compound B for 18 days caused a significant tumor growth inhibition of 80%. See Figure 4a. A significant tumor growth inhibition of 96% was observed with Compound A at 100 mg/kg q2d, whereas Compound A at 30 mg/kg qd lead to a lower but still significant TGI of 76%. The combination of Compound B 30 mg/kg qd with Compound A 30 mg/kg qd or with Compound A 100 mg/kg q2d resulted in significant efficacy associated with 15% and 39% regression, respectively, which was significantly higher than either of the single agent treatments alone.

[0405] As a single agent Compound B dosed at 30 mg/kg qd was generally well tolerated, with a body weight loss of 1.5-6.9% and no dose omission. Administration of Compound A dosed at 30 mg/kg qd was well tolerated with 4 doses skipped at the beginning of the study, which were not compound-related. Compound A dosed at 100 mg/kg q2d was also well tolerated with I dose skipped at the beginning of the study, which was not compound-related. The combination of Compound B at 30 mg/kg qd with Compound A at 30 mg/kg qd was fairly well tolerated with body weight loss of 1 to 8% and 2 doses skipped). However, the combination of Compound B at 30 mg/kg qd with Compound A at 100 mg/kg q2d was associated with body weight loss of 2 to 11% and 13 doses skipped within the first 10 days; however, body weights at the end of the study were not significantly different from the vehicle-treated control group. Single agent administration of Compound B and Compound A were well tolerated with minimal dose skipping. When administered in combination, minor body weight loss was observed that necessitated dose skipping primarily in the 100 mg/kg q2d group.

Breast Cancer Xenograft Model - A Compound of Formula I in Combination with Compound B - Reference example

[0406] Compound A was tested both as a single agent and in combination with Compound B, an EGFR inhibitor, in a breast tumor model. The MCF7 human breast carcinoma cell line harbors a heterozygous, activating mutation in PI3K (PI3KCA/E545K) and expresses wild-type EGFR.

[0407] Compound B was administered orally once-daily (qd) at 30 mg/kg, and Compound A was administered once-daily at 30 mg/kg or once every other day (q2d) at 100 mg/kg. Combination therapies consisted of Compound B together with Compound A at 30 mg/kg qd or 100 mg/kg q2d. Single agent administration of Compound B at 30 mg/kg qd for 14 days caused a tumor growth inhibition of 38%-61%. See Figures 4b-1 and 4b-2. A significant tumor growth inhibition of 83%-91% was observed with Compound A at 100 mg/kg q2d, whereas Compound A at 30 mg/kg qd lead to a lower but still significant TGI of 57%. The combination of Compound B at 30 mg/kg qd with Compound A at 100 mg/kg q2d resulted in a significant efficacy associated with 16-22% regression, which was significantly higher than either of the single agent treatments alone. Combining Compound B at 30 mg/kg qd with Compound A at 30 mg/kg qd lead to a lower but still significant tumor growth inhibition of 66%, but did not add any benefit to the anti-tumor efficacy of the single treatments.

[0408] As a single agent Compound B dosed at 30 mg/kg qd was generally well tolerated, with a non significant final body weight loss of 4.5 to 6.1% and 7 to 13 dose omissions. Administration of Compound A at 30 mg/kg qd and 100 mg/kg q2d was well tolerated with minimal dose skipping and body weight loss. The combination of Compound B at 30 mg/kg qd with Compound A at 30 mg/kg qd lead to a body weight loss of 4 to 13% throughout the study and 14 doses skipped mostly within the first 9 days. The combination of Compound B at 30 mg/kg qd with Compound A at 100 mg/kg q2d was associated with a body weight loss of 3.7 to 13% throughout the study and 20 to 32 dose omissions.

Breast Cancer Xenograft Model - A Compound of Formula I in Combination with Erlotinib

[0409] Compound A was tested both as a single agent and in combination with erlotinib, in an erolitinib-resistant tumor model with elevated PI3K signaling.

[0410] MDA-MB-468 is a human breast carcinoma cell line that has an increase in the copy number of the EGFR gene and a homozygous deletion of PTEN. In vitro treatment of these cells with EGFR inhibitors such as erlotinib inhibits EGFR activity but fails to downregulate the PI3K pathway. Oral administration of erlotinib at 100 mg/kg qd to mice bearing MDA-MB-468 tumors resulted in significant but incomplete tumor growth inhibition. See Figure 5. Oral administration of Compound A at 100mg/kg qd resulted in a similar level of tumor growth inhibition. While tumor growth was inhibited substantially with Compound A alone, the combination of the two agents was superior to either agent alone and resulted in a regression of the tumors.

[0411] Mice administered Compound A at 100 mg/kg qd exhibited a modest (∼3%) loss in body weight comparable to vehicle controls. Mice administered erlotinib exhibited an apparent decrease in their rate of body weight gain relative to vehicle controls. Coadministration with erlotinib resulted in a substantial loss in body weight in mice treated with Compound A (19% body weight loss from start of dosing). Consistent with these data, only minimal dose-skipping was required when Compound A was administered as monotherapy (1-3 doses skipped), but substantial dose-skipping was required for Compound A when erlotinib was coadministered. The fact that tumor regression was observed despite dose skipping suggests that use of an intermittent dosing schedule could maintain efficacy and improve tolerability. These results support the use of a Compound of Formula I in combination with erlotinib in tumors expressing EGF receptors and harboring PTEN deletions.

[0412] The foregoing invention has been described in some detail by way of illustration and example, for purposes of clarity and understanding. It will be obvious to one of skill in the art that changes and modifications may be practiced within the scope of the appended claims. Therefore, it is to be understood that the above description is intended to be illustrative and not restrictive. The scope of the invention should, therefore, be determined not with reference to the above description, but should instead be determined with reference to the following appended claims, along with the full scope of equivalents to which such claims are entitled.

Claims

1. A compound which is:

or a single isomer or tautomer thereof where the compound is optionally as a pharmaceutically acceptable salt and additionally optionally as a hydrate and additionally optionally as a solvate thereof; for use in combination with one or more treatments independently selected from one or more chemotherapeutic agents selected from the group consisting of a platin, a taxane, rapamycin, and erlotinib for the treatment of cancer.

2. The compound or single isomer or tautomer thereof of Claim 1, where the cancer is selected from breast cancer, colon cancer, rectal cancer, endometrial cancer, gastrointestinal carcinoid tumors, gastrointestinal stromal tumors, glioblastoma, hepatocellular carcinoma, small cell lung cancer, non-small cell lung cancer, melanoma, ovarian cancer, cervical cancer, pancreatic cancer, prostate carcinoma, acute myelogenous leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, and thyroid carcinoma.

3. The compound of claim 1 where the treatment is one chemotherapeutic agent where the chemotherapeutic agent is taxol.

4. The compound of claim 1 where the treatment is one chemotherapeutic agent where the chemotherapeutic agent is rapamycin.

5. The compound of claim 1 where the treatment is one chemotherapeutic agent where the chemotherapeutic agent is carboplatin.

6. The compound of claim 1 where the treatment is one chemotherapeutic agent where the chemotherapeutic agent is erlotinib.

7. The compound of claim 1 where the cancer is selected from prostate cancer, non-small cell lung cancer, and breast cancer.

8. The compound of claim 1 where the chemotherapeutic agent is taxol and the cancer is prostate cancer.

9. The compound of claim 1 where the chemotherapeutic agent is rapamycin and the cancer is prostate cancer.

10. The compound of claim 1 where the chemotherapeutic agent is carboplatin and the cancer is non-small cell lung cancer.

11. The compound of claim 1 where the chemotherapeutic agent is erlotinib and the cancer is breast cancer.

Ansprüche

1. Eine Verbindung, die folgende ist:

oder ein einzelnes Isomer oder Tautomer davon, wobei die Verbindung wahlweise als ein pharmazeutisch akzeptables Salz und außerdem wahlweise als ein Hydrat und außerdem wahlweise als ein Solvat davon vorliegt; zur Verwendung in Kombination mit einer oder mehreren Behandlungen, die unabhängig ausgewählt sind aus einem oder mehreren Chemotherapeutika, ausgewählt aus der Gruppe, die aus einem Platin, einem Taxan, Rapamycin und Erlotinib besteht, zur Behandlung von Krebs.

2. Verbindung oder einzelnes Isomer oder Tautomer davon gemäß Anspruch 1, wobei der Krebs ausgewählt ist aus Brustkrebs, Dickdarmkrebs, Rektalkrebs, Endometriumkrebs, gastrointestinalen Karzinoidtumoren, gastrointestinalen Stromatumoren, Glioblastom, hepatozellulärem Karzinom, kleinzelligem Lungenkrebs, nichtkleinzelligem Lungenkrebs, Melanom, Eierstockkrebs, Gebärmutterhalskrebs, Bauchspeicheldrüsenkrebs, Prostatakarzinom, akuter myeloischer Leukämie, chronischer myeloischer Leukämie, Non-Hodgkin-Lymphom und Schilddrüsenkarzinom.

3. Verbindung gemäß Anspruch 1, wobei die Behandlung ein Chemotherapeutikum ist, wobei das Chemotherapeutikum Taxol ist.

4. Verbindung gemäß Anspruch 1, wobei die Behandlung ein Chemotherapeutikum ist, wobei das Chemotherapeutikum Rapamycin ist.

5. Verbindung gemäß Anspruch 1, wobei die Behandlung ein Chemotherapeutikum ist, wobei das Chemotherapeutikum Carboplatin ist.

6. Verbindung gemäß Anspruch 1, wobei die Behandlung ein Chemotherapeutikum ist, wobei das Chemotherapeutikum Erlotinib ist.

7. Verbindung gemäß Anspruch 1, wobei der Krebs ausgewählt ist aus Prostatakrebs, nichtkleinzelligem Lungenkrebs und Brustkrebs.

8. Verbindung gemäß Anspruch 1, wobei das Chemotherapeutikum Taxol ist und der Krebs Prostatakrebs ist.

9. Verbindung gemäß Anspruch 1, wobei das Chemotherapeutikum Rapamycin ist und der Krebs Prostatakrebs ist.

10. Verbindung gemäß Anspruch 1, wobei das Chemotherapeutikum Carboplatin ist und der Krebs nichtkleinzelliger Lungenkrebs ist.

11. Verbindung gemäß Anspruch 1, wobei das Chemotherapeutikum Erlotinib ist und der Krebs Brustkrebs ist.

Revendications

1. Un composé qui est :

ou un isomère unique ou tautomère de celui-ci où le composé est facultativement sous la forme d'un sel pharmaceutiquement acceptable et facultativement encore sous la forme d'un hydrate et facultativement encore sous la forme d'un solvate de celui-ci ; destiné à être utilisé en combinaison avec un ou plusieurs traitements sélectionnés indépendamment parmi un ou plusieurs agents chimiothérapeutiques sélectionnés dans le groupe consistant en un platine, un taxane, la rapamycine et l'erlotinib pour le traitement du cancer.

2. Le composé ou l'isomère unique ou tautomère de celui-ci de la revendication 1, où le cancer est sélectionné parmi le cancer du sein, le cancer du côlon, le cancer du rectum, le cancer de l'endomètre, les tumeurs carcinoïdes gastro-intestinales, les tumeurs stromales gastro-intestinales, le glioblastome, le carcinome hépatocellulaire, le cancer du poumon à petites cellules, le cancer du poumon non à petites cellules, le mélanome, le cancer de l'ovaire, le cancer du col de l'utérus, le cancer du pancréas, le carcinome de la prostate, la leucémie myéloïde aiguë, la leucémie myéloïde chronique, le lymphome non-hodgkinien, et le carcinome de la thyroïde.

3. Le composé de la revendication 1 où le traitement est un agent chimiothérapeutique où l'agent chimiothérapeutique est le taxol.

4. Le composé de la revendication 1 où le traitement est un agent chimiothérapeutique où l'agent chimiothérapeutique est la rapamycine.

5. Le composé de la revendication 1 où le traitement est un agent chimiothérapeutique où l'agent chimiothérapeutique est le carboplatine.

6. Le composé de la revendication 1 où le traitement est un agent chimiothérapeutique où l'agent chimiothérapeutique est l'erlotinib.

7. Le composé de la revendication 1 où le cancer est sélectionné parmi le cancer de la prostate, le cancer du poumon non à petites cellules, et le cancer du sein.

8. Le composé de la revendication 1 où l'agent chimiothérapeutique est le taxol et le cancer est le cancer de la prostate.

9. Le composé de la revendication 1 où l'agent chimiothérapeutique est la rapamycine et le cancer est le cancer de la prostate.

10. Le composé de la revendication 1 où l'agent chimiothérapeutique est le carboplatine et le cancer est le cancer du poumon non à petites cellules.

11. Le composé de la revendication 1 où l'agent chimiothérapeutique est l'erlotinib et le cancer est le cancer du sein.

Drawing