| (11) | EP 2 178 869 B1 |
(12) | EUROPEAN PATENT SPECIFICATION |
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(54) | INDOLE COMPOUNDS AS AN INHIBITOR OF CELLULAR NECROSIS INDOLVERBINDUNGEN ALS HEMMER VON ZELLNEKROSE COMPOSÉS D'INDOLE EN TANT QU'INHIBITEURS DE NÉCROSE CELLULAIRE |
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Note: Within nine months from the publication of the mention of the grant of the European patent, any person may give notice to the European Patent Office of opposition to the European patent granted. Notice of opposition shall be filed in a written reasoned statement. It shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). |
[Technical Field]
[Background Art]
[Detailed Description of the Invention]
[Technical Subject to be Solved]
[Means for Solving the Technical Subject]
n denotes a number of 0 to 3,
A represents 5 membered heteroaryl or heterocycle each of which has 1 to 3 hetero atoms selected from N, O and S,
R1 represents R5-X-B-X'-,
B represents a direct bond, or represents 3~10 membered heterocycle or heteroaryl each of which has 1 to 4 hetero atoms selected from N, O and S,
X and X' independently of one another represent a direct bond, or are selected from the group consisting of -NR6-, -CO-, -CONR6-, -CO2-, -OC(O)-, -S(O)m-, -O-(CH2)m-, -(CH2)m-O-, -(CH2)m-, -NR6CO-, -(R6O)2P(O)- and -NHCO2-, wherein m denotes a number of 0 to 3, and R6 represents hydrogen, alkyl or cycloalkyl,
R5 represents hydrogen, nitrile, hydroxy, alkyl, alkoxy, cycloalkyl or aryl, or represents 3~10 membered monocyclic or fused cyclic heterocycle or heteroaryl each of which has 1 to 3 hetero atoms selected from N, O and S, and is optionally substituted by oxo or alkyl, or
R5 and R6 may together form a 4~8 membered cycle,
R2 represents -(CR8R9)p-Y-R7,
p denotes a number of 0 to 2,
R8 and R9 independently of one another represent hydrogen or alkyl, or may together form a 4~8 membered cycle,
Y represents a direct bond, or is selected from the group consisting of -O-, -S-, -NR6-, -NR6C(O)-, -CO2-, -C(O)-, -C(O)NR6-, -S(O)q-, and -S(O)qNR6-, wherein q denotes a number of 0 to 2,
R7 represents hydrogen, halogen, cyano, hydroxy, nitro, alkyl, cycloalkyl or aryl, or represents 3~10 membered, heterocycle or heteroaryl each of which has 1 to 3 hetero atoms selected from N, S and O and which optionally contains oxo,
R3 represents hydrogen, alkyl, -(CH2)q-cycloalkyl or -(CH2)q-heterocycle,
R4 represents cycloalkyl optionally containing oxo
where alkyl, alkoxy, aryl, cycloalkyl, heterocycle and heteroaryl may be optionally substituted, and the substituents are one or more selected from the group consisting of hydroxy, halogen, nitrile, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkylsulfonyl, carboxyalkyl, alkylcarbonyloxy, alkylthio, alkyloxycarbonyl, alkylaminocarbonyl, arylalkoxy and oxo, and pharmaceutically acceptable salts or optical isomer (R or S isomer), racemate, mixture of diastereomers, or individual diastereomer thereof.n denotes a number of 0 to 3,
A represents 5 membered heteroaryl or heterocycle each of which has 1 to 3 hetero atoms selected from N, O and S,
R1 represents R5-X-B-X'-,
B represents a direct bond, or represents 3~10 membered heterocycle or heteroaryl each of which has 1 to 4 hetero atoms selected from N, O and S,
X and X' independently of one another represent a direct bond, or are selected from the group consisting of -NR6-, -CO-, -CONR6-, -CO2-, -OC(O)-, -S(O)2-, -O-(CH2)m-, -(CH2)m-O-, -(CH2)m-, -NR6CO-, -(R6O)2P(O)- and -NHCO2-, wherein m denotes a number of 0 to 3, and R6 represents hydrogen, C1-C6-alkyl or C3-C6-cycloalkyl,
R5 represents hydrogen, nitrile, hydroxy, C1-C6-alkyl, halogeno-C1-C6-alkyl, hydroxy-C1-C6-alkyl, C4-C6-cycloalkyl, phenyl or halophenyl, or represents 5~10 membered monocyclic or fused cyclic heterocycle or heteroaryl each of which has 1 to 3 hetero atoms selected from N, O and S, and is optionally substituted by oxo or halogeno-C1-C6-alkyl, or
R5 and R6 may together form a 4~8 membered cycle,
R2 represents -(CR8R9)p-Y-R7,
p denotes a number of 0 to 2,
R8 and R9 independently of one another represent hydrogen or C1-C6-alkyl, or may together form a 5~6 membered cycle,
Y represents a direct bond, or is selected from the group consisting of -O-, -NR6-, -NR6C(O)-, -C(O)-, -CO2- -C(O)NR6-, and -S(O)q-, wherein q denotes a number of 0 to 2,
R7 represents hydrogen, halogen, cyano, hydroxy, C1-C6-alkyl, hydroxy-C1-C6-alkyl or halogeno-C1-C6-alkyl, represents phenyl optionally substituted by C1-C6-alkylsulfonyl, or represents 5~6 membered heterocycle or heteroaryl each of which has 1 to 3 hetero atoms selected from N and O,
R3 represents hydrogen, C1-C6-alkyl, -(CH2)-C3-C6-cycloalkyl or -(CH2)-heterocycle wherein the heterocycle is a 5~6 membered cycle having 1 to 2 hetero atoms selected from N, O and S,
R4 represents C3-C6 cycloalkyl optionally containing oxo.
Cyclopentyl-[2-(4,5-dihydro-1,3-thiazol-2-yl)-1H-indol-7-yl]-amine;
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-4-yl]-methanol;
[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;
[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;
(R)-2-[7-cyclopentylamino-5-(hydroxymethyl)-1H-indol-2-yl]-4,5-dihydrothiazol-4-yl-methanol;
[(S)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(S)-2-(5-methyl-7-(4,4-difluorocyclohexan-4-yl)amino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(S)-2-(5-methyl-7-cyclobutylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(S)-2-(5-methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-4-yl]-methanol;
[(R)-2-(5-(dimethylamino)methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-(pyrrol-3-yl)methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-methanol;
[(R)-2-(5-(1,3-imidazol-1-yl)methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-(pyrazol-1-yl)methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-methanol;
[(R)-2-(5-acetylamino-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-phenoxymethyl-7-cyclopentylatnino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acetic acid;
[(R)-2-(5-(pyrrolidin-1-yl)methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;
Cyclopentyl-[5-chloro-2-((R)-4-isobutyl-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl)-amine;
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid ethyl ester;
Cyclopentyl-[5-fluoro-2-((R)-4-ethyl-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl]-amine;
{(R)-2-[7-(methyl-cyclopentyl)amino-5-fluoro-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-4-yl}-methanol;
[(S)-2-(5-ethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;
[(S)-2-(5-ethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(S)-2-(5-ethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;
[(R)-2-(5-methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-carboxylic acid ethyl ester;
[(S)-2-(5-phenoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;
[(R)-2-(5-bromo-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-(pyridin-3-yl)oxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-methanol;
[(R)-2-(5-methanesulfonylmethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-(isoindol-1,3-dion-2-yl)methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(3-bromo-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid ethyl ester;
[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid ethyl ester;
[(R)-2-(5-methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;
[(R)-2-(5-methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-ethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-propyloxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-phenoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-(pyridin-3-yl)oxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acetic acid methyl ester;
[(R)-2-(5-(pyridin-3-yl)oxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acetic acid;
[(R)-2-(5-methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;
[(R)-2-(5-methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-(4-(methanesulfonyl)phenoxy)-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-phenoxymethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acetic acid methyl ester;
[(R)-2-(5-phenylaminomethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acetic acid methyl ester;
[(R)-2-(5-methanesulfonylmethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;
[(R)-2-(5-methanesulfonylmethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-methanesulfonylmethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl acetamide;
3-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,3-dihydro-thiazol-4-yl]-propionic acid;
[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propanol;
3-[(R)-2-(5-methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid ethyl ester;
3-[(R)-2-(5-methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;
3-[(R)-2-(5-phenoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;
3-[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid ethyl ester;
3-[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;
3-[(R)-2-(5-bromo-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid ethyl ester;
3-[(R)-2-(5-bromo-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;
3-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;
3-[(R)-2-(5-methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;
3-[(R)-2-(5-ethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid ethyl ester;
3-[(R)-2-(5-ethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;
3-[(R)-2-(5-trifluoromethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionic acid ethyl ester;
3-[(R)-2-(5-trifluoromethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionic acid;
[(S)-2-(5-methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-oxazol-4-yl]-acetic acid;
[(S)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-oxazol-4-yl]-acetic acid;
[2-((4S,5R)-5-aminomethyl-4-benzyl-dihydro-oxazol-2-yl)-5-chloro-1H-indol-7-yl]-cyclopentyl-amine;
{2-[(R)-5-((S)-1-amino-2-phenyl-ethyl)-4,5-dihydro-oxazol-2-yl]-5-chloro-1H-indol-7-yl}-cyclopentyl-amine;
Cyclopentyl-[2-(4,5-dihydro-oxadiazol-2-yl)-1H-indol-7-yl]-amine;
[2-(5-Methyl-7-cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-methanol;
[2-(5-Methyl-7-cyclopentylamino-1H-indol-2-yl)-thiazol-5-yl]-methanol;
[2-(5-Methyl-7-cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-carboxylic acid ethyl ester;
[2-(5-Methyl-7-cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-carboxylic acid;
[2-(7-Cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-methanol;
[2-(7-Cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-carboxylic acid methyl ester;
2-[(R)-2-(5-chloro-7-cyclopentylamimo-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-morpholin-4-yl-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)ethylamino-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)propylamino-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-methylamino-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-dimethylamino-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-[4-(methyl)piperazin-1-yl]-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(3-dimethylaminopyrrolidin-1-yl)-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(piperidin-4-yl)-ethanone;
2-[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(4-(methyl)piperazin-1-yl)-ethanone;
2-[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)ethylamino-ethanone;
2-[(R)-2-(5-methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(methylamino)-4-yl-ethanone;
2-[(R)-2-(5-methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)-ethanone;
2-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-methylamino-ethanone;
2-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)ethylamino-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(4-(methyl)piperazin-1-yl)-ethanone;
Cyclopentyl-{5-methanesulfonylmethyl-2-[(R)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine;
1-(4-{2-[(R)-2-(7-cyclopentylamino-5-methanesulfonylmethyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanone;
Cyclopentyl-[2-((R)-4-pyrrolidin-1-ylmethyl-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl]-amine;
{5-Chloro-2-[(R)-4-(2-dimethylamino-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine;
{5-Chloro-2-[(R)-4-(2-piperazin-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine;
(5-Chloro-2-{(R)-4-[2-(4-ethanesulfonyl-piperazin-1-yl)-ethyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
1-(4-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanone;
{5-Chloro-2-[(R)-4-(2-pyrazol-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine;
(S)-1-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-pyrrolidine-2-carboxylic acid;
{5-Chloro-2-[(R)-4-(2-methanesulfonyl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine;
3-{2-[(R)-2-(3-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-5-methyl-3H-imidazole-4-carboxylic acid ethyl ester;
3-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-5-methyl-3H-imidazole-4-carboxylic acid;
Cyclopentyl-{2-[(R)-4-(2-methoxy-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine;
[2-((R)-4-aminomethyl-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl]-cyclopentylamine;
{2-[(R)-4-((R)-3-amino-pyrrolidin-1-ylethyl)-4,5-dihydro-thiazol-2-yl]-5-chloro-1H-indol-7-yl}-cyclopentyl-amine;
4-[(R)-2-(7-cyclopentylamino-5-ethoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-ylethyl]-piperazin-2-one;
{2-[(R)-4-((S)-3-amino-pyrrolidin-1-ylethyl)-4,5-dihydro-thiazol-2-yl]-5-chloro-1H-indol-7-yl}-cyclopentyl-amine;
(5-Chloro-2-{(S)-4-[2-(3-dimethylamino-phenyl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
1-(4-{2-[(S)-2-(7-cyclopentylamino-5-chloro-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanone;
1-(4-{2-[(S)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanone;
(5-Methoxy-2-{(R)-4-[2-(pyrrolidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Methanesulfonylmethyl-2-{(S)-4-[(2-oxopiperazin-4-yl)-ethyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
1-(4-{2-[(R)-2-(7-cyclopentylamino-5-chloro-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-2-yl)-ethanone;
(5-Chloro-2-{(R)-4-[4-methyl-piperazin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-IH-indol-7-yl)-cyclopentyl-amine;
(5-Chloro-2-{(R)-4-[4-(hydroxy)piperidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Chloro-2-{(R)-4-[2-oxopiperazin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Chloro-2-{(R)-4-[(piperidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Chloro-2-{(R)-4-[(1,1-dioxo-thiomorpholin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Chloro-2-{(R)-4-[(2-oxopyrrolidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Fluoro-2-{(R)-4-(2-aminoethyl)-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
1-(4-{2-[(R)-2-(5-fluoro-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanone;
(5-Fluoro-2-{(R)-4-[(morpholin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Fluoro-2-{(R)-4-(2-dimethylamino-ethyl)-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Fluoro-2-{(R)-4-[(pyrrolidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Fluoro-2-{(R)-4-[(1,1-dioxo-thiomorpholin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Fluoro-2-{(R)-4-[(2-oxopyrrolidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
1-(4-{2-[(5-Fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]ethyl}-piperazin-1-yl)-2-hydroxy-ethanone;
(5-Fluoro-2-{(R)-4-[methanesulfonyl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(2-{(R)-4-[2-dimethylamino-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(2-{(R)-[(piperidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
1-(4-{2-[(R)-2-(5-methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanone;
1-(4-{2-[(R)-2-(7-cyclopentylamino)-5-chloro-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propyl}-piperazin-1-yl)-ethanone,
2-{(R)-4-[(morpholin-4-yl)-methyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Chloro-2-{(R)-4-[(morpholin-4-yl)-propyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(2-{(R)-4-[2-dimethylamino-methyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Chloro-2-{(S)-4-[(morpholin-4-yl)-ethyl]-4,5--dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
1-(4-{2-[(S)-2-(5-phenoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanone;
(5-Phenoxy-2-{(S)-4-[(piperazin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
t-Butyl-(4-{2-[(S)-2-(5-phenoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazine-1-carboxylate;
Cyclopentyl-(5-phenoxy-2-{(S)-4-[2-(3-fluoromethyl-5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-amine;
(5-Phenoxy-2-{(S)-4-[2-oxopiperazin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(4-{2-[(S)-2-(5-phenoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-oxoran-2-yl-methanone;
(5-Phenoxy-2-{(S)-4-[(pyridin-2-yl)piperazine-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Phenoxy-2-{(S)-4-[(2-fluorophenyl)piperazine-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Chloro-2-{(S)-4-[2-oxopiperazin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Phenoxy-2-{(S)-4-[(3S)-3-(amino)pyrrolidin-1-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
1-(4-{2-[(S)-2-(5-phenoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}piperazin-1-yl)-ethanone;
(5-Chloro-[(S)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl])-pyrrolidin-3-yl-acetamide;
(5-Phenoxy-2-{(S)-4-[4-(benzyl)piperazin-1-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Phenoxy-2-{(R)-4-[pyrrolidin-1-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Phenoxy-2-{(S)-4-[pyrrolidin-1-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Methyl-2-{(S)-4-[2-oxopiperazin-4-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-4,4-difluorocyclohexyl-amine;
(5-Methyl-2-{(S)-4-[morpholin-4-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-4,4-difluorocyclohexyl-amine;
1-(4-{2-[(R)-2-(5-methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanone;
[(R)-2-(5-aminomethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
Furan-2-carboxylic acid [7-cyclopentylamino-2-((R)-4-hydroxymethyl-4,5-dihydro-thiazol-2-yl)-1H-indol-5-ylmethyl]-amide;
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-ylmethoxy]-acetic acid methyl ester;
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-ylmethoxy]-acetic acid;
Cyclopentyl-{2-[(R)-4-(3-cyclopentyl-[1,2,4]oxadiazol-5-ylmethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine; and
Cyclopentyl-{2-[(R)-4-(3-piperidin-1-yl-[1,2,4]oxadiazol-5-ylmethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine.
[Effect]
[Best Mode for Carrying Out the Invention]
Preparation 1: 4-(Pyridin-3-yloxy)phenylamine
Step A: 4-(Pyridin-3-yl)oxy-1-nitrobenzene
Step B: 4-(Pyridin-3-yloxy)phenylamine
Preparation 2: 4-(4-Methanesulfonyl-phenoxy)phenylamine
Step A: 1-(4-Methylsulfanylphenoxy)-4-nitrobenzene
Step B: 4-(4-Methanesulfonyl-phenoxy)nitrobenzene
Step C: 4-(4-Methanesulfonyl-phenoxy)phenylamine
Preparation 3: 4-Ethoxy-2-nitro-phenylamine
Step A: 4-Ethoxy-1-acetylaminobenzene
Step B: 4-Ethoxy-2-nitro-1-phenylamine
Preparations 4 to 13:
Preparation | R2 | Mass [M+H] |
4 | -O-(pyridin-3-yl) | 231 |
5 | -O-(4-methanesulfonylphenyl) | 308 |
6 | methoxy | 168 |
7 | phenoxy | 231 |
8 | fluoro | 156 |
9 | bromo | 217 |
10 | NAc | 195 |
11 | -O-(n-Pr) | 196 |
12 | -O-CF3 | 222 |
13 | chloro | 172 |
Preparation 14: 5-Chloro-7-nitro-1H-indole-2-carboxylic acid methyl ester
<Method A>
Step A: (4-Chloro-2-nitro-phenyl)hydrazine hydrochloride
Step B: 2-[(4-Chloro-2-nitro-phenyl)hydrazono]propionic acid methyl ester
Step C: 5-Chloro-7-nitro-1H-indole-2-carboxylic acid methyl ester
<Method B>
Step A: 2-[(4-Chloro-2-nitro-phenyl)-hydrazono]-propionic acid methyl ester
Step B: 5-Chloro-7-nitro-1H-indole-2-carboxylic acid methyl ester
Preparations 15 to 26:
Preparation | R | R2 | 1H-NMR |
15 | methyl | methyl | (500HMz, DMSO-d6); δ 11.25(br s, 1H), 8.08(3, 1H), 7.96(s, 1H), 7.32(s, 1H), 3.87(s, 3H), 2.44(s, 3H) |
16 | methyl | methoxy | (400HMz, DMSO-d6); δ 11.26(br s, 1H), 7.84(s, 1H), 7.80(s, 1H), 7.35(s, 1H), 3.91(s, 3H), 3.89(s, 3H) |
17 | methyl | hydrogen | 1H-NMR (500HMz, DMSO-d6); δ 11.36(br s, 1H), 8.23(d, 1H), 8.17(d, 1H), 7.42(s, 1H), 7.32(t, 1H), 3.88(s, 3H) |
18 | ethyl | fluoro | (400HMz, DMSO-d6); δ 11.55(br s, 1H), 8.16(m, 1H), 8.10(m, 1H), 7.42(s, 1H), 4.40(q, 2H), 1.36(t, 3H) |
19 | ethyl | ethoxy | (400HMz, DMSO-d6); δ 10.20(br s, 1H), 7.86(s, 1H), 7.51(s, 1H), 7.26(s, 1H), 4.13(m, 2H), 3.98(s, 3H), 1.47(m, 3H) |
20 | methyl | bromo | (400HMz, CDCl3); δ 10.33(br s, 1H), 8.41 (s, 1H), 8.18(s, 1H), 7.30(d, J=4.0Hz, 1H), 4.01 (s, 3H) |
21 | methyl | phenoxy | (400HMz, CDCl3); δ 10.26(br s, 1H), 8.05(s, 1H), 7.69(s, 1H), 7.39(m, 2H), 7.26(s, 1H), 7.15(m, 1H), 7.01(m, 2H), 4.00(s, 3H) |
22 | ethyl | -O-(4-methanesulfonyl) | (400HMz, DMSO-d6); δ 8.099s, 1H), 10.20(br s, 1H), 7.86(s, 1H), 7.51 (s, 1H), 7.26(s, 1H), 4.13(m, 2H), 3.98(s, 3H), 1.47(m, 3H) |
23 | ethyl | -O-(pyridin-3-yl) | 1H-NMR (400HMz, CDCl3); δ 10.32(br s, 1H), 8.51~8.47(m, 2H), 8.05(d, J=2.4Hz, 1H), 7.73(d, J=2.0Hz, 1H), 7.42~7.35(m, 2H), 7.31(d, J=2.4Hz, 1H), 4.48(q, 2H), 1.47(t, 3H) |
24 | ethyl | -O-(n-Pr) | (400HMz, DMSO-d6); δ 10.12(brs, 1H), 7.92(s, 1H), 7.51(s, 1H), 7.24(s, 1H), 4.44(m, 2H), 4.01(m, 2H), 1.91(m, 2H), 1.44(m, 3H), 1.08(m, 3H) |
25 | ethyl | -O-CF3 | (400HMz, DMSO-d6); δ 10.34(br s, 1H), 7.91(s, 1H), 7.80(s, 1H), 7.45(s, 1H), 4.34(m, 2H), 1.45(m, 3H) |
26 | ethyl | NAc | (400HMz, DMSO-d6); δ 11.26(s, 1H), 10.31(s, 1H), 8.55(s, 1H), 8.44(s, 1H), 7.45(s, 1H), 4.40(q, 2H), 2.11(s, 3H), 1.36(t, 3H) |
Preparation 27: (R)-3-amino-4-(4-methoxy-benzylsulfanyl)-butyric acid methyl, ester hydrochloride
Step A: (R)-2-amino-3-(4-methoxy-benzylsulfanyl)-propionic acid
Step B: (R)-2-BOC-amino-3-(4-methoxy-benzylsulfanyl)-propionic acid
Step C: [(R)3-diazo-1-(4-methoxy-benzylsulfanylmethyl)-2-oxo-propyl]-carbamic acid t-butyl ester
Step D: (R)-3-t-butoxycarbonylamino-4-(4-methoxy-benzylsulfanyl)-butyric acid methyl ester
Step E: (R)-3-amino-4-(4-methoxy-benzylsulfanyl)-butyric acid methyl ester
Preparation 28: Ethyl (R)-3-amino-4-(4-methoxy-benzylsulfanyl)-butyrylate hydrochloride
Preparation 29: (R)-4-amino-5-(4-methoxy-benzylsulfanyl)-pentanoic acid ethyl ester hydrochloride
Step A: (TR)-4-BOC-amino-5-hydroxy-pentanoic acid ethyl ester
Step B: (R)-4-BOC-amino-5-methanesulfonyloxy-pentanoic acid ethyl ester
Step C: (R)-4-BOC-amino-5-(4-methoxy-benzylsulfanyl)-pentanoic acid ethyl ester
Step D: (R)-4-amino-5-(4-methoxy-benzylsulfanyl)-pentanoic acid ethyl ester hydrochloride
Preparation 30: (S)-3-amino-4-(methoxy-benzylsulfanlyl)-butyric acid isopropyl ester
Step A: (S)-2-BOC-amino-succinic acid 4-isopropylester 1-methylester
Step B: (S)-3-amino-4-(methoxy-benzylsulfanyl)-butyric acid isopropyl ester
Preparation 31: 2,2-Dimethyl-propionic acid (R)-2-amino-3-(4-methoxy-benzylsulfanyl)-propyl ester
Step A: (R)-2-amino-3-(4-methoxy-benzylsulfanyl)-propionic acid methyl ester
Step B: (R)-2-BOC-amino-3-(4-methoxy-benzylsulfanyl)-propionic acid methyl ester
Step C: [(R)-2-hydroxy-1-(4-methoxy-benzylsulfanylmethyl)-ethyl]-carbamic acid t-butyl ester
Step D: 2.2-Dimethylpropionic acid (R)-2-t-butoxycarbonylamino-3-(4-methoxy-benzylsulfanyl)-propyl ester
Step E: 2,2-Dimethyl-propionic acid (R)-2-amino-3-(4-methoxy-benzylsulfanyl)-propyl ester
Preparation 32: 2,2-Dimethyl-propionic acid (S)-2-amino-3-(4-metboxy-benzylsulfanyl)-propyl ester
Step A: (S)-2-BOC-amino-3-methylsulfonyloxy-propionic acid methyl ester
Step B: (S)-2-BOC-amino-3-(4-methoxy-benzylsulfanyl)propionic acid methyl ester
Step: (S)-2-t-butoxycarbonylamino-3-(4-methoxy-benzylsulfanyl)-propanol
Step D: 2,2-Dimethyl-propionic acid (R)-2-amino-3-(4-methoxy-benzylsulfanyl)-propyl ester
Preparation 33: 2-Amino-3-(4-methoxy-benzylsulfanyl)-propionic acid methyl ester
Preparation 34: 2-[(4-Methoxy-benzylsulfanyl)ethylamine
Preparation 35: (R)-1-[(4-methoxy-benzylsulfanyl)methyl]propylamine
Preparation 36: (R)-1-[(4-methoxy-benzylsulfanyl)methyl]-2-methyl-1-propylamine
Preparation 37: 5-Bromomethyl-7-nitro-indole-2-carboxylic acid methyl ester
Step A: 1-BOC-5-methyl-7-nitro-indole-2-carboxylic acid methyl ester
Step B: 1-BOC-5-bromomethyl-7-nitro-indole-2-carboxylic acid methyl ester
Step C: 5-Bromomethyl-7-nitro-indole-2-carboxylic acid methyl ester
Preparation 38: 5-Hydroxymethyl-7-nitro-1H-indole-2-carboxylic acid
Step A: 1-BOC-5-acetoxymethyl-7-nitro-indole-2-carboxylic acid methyl ester
Step B: 5-Acetoxymethyl-7-nitro-1H-indole-2-carboxylic acid methyl ester
Step C: 5-Hydroxymethyl-7-nitro-1H-indole-2-carboxylic acid
Preparation 39: 5-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-7-nitro-1H-indole-2-carboxylic acid methyl ester
Step A: 1-BOC-5-(1,3-dioxo-1,3-dihydro-isoindol-2-ylmethyl)-7-nitro-1H-indole-2-carboxylic acid methyl ester
Step B: 5-(1,3-Dioxo-1,3-dihydro-isoindol-2-ylmethyl)-7-nitro-1H-indole-2-carboxylic acid methyl ester
Preparation 40: 2,2-Dimethyl-propionic acid (R)-2-(7-nitro-1H-indol-2-yi)-4,5-dihydro-thiazol-4-ylmethyl ester
Step A: 7-Nitro-1H-indole-2-carboxylic acid
Step B: 2,2-Dimethyl-propionic acid (R)-3-(4-methoxy-benzylsulfanyl)-2-[(7-nitro-1H-indole-2-carbonyl)-amino]-propyl ester
Step C: 2,2-Dimethyl-propionic acid [(R)-2-(7-nitro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methyl ester
Preparations 41: 2,2-Dimethyl-propionic acid (R)-2-[(5-chloromethyl-7-nitro-1H-indol-2-yl)-(4,5-dihydro-thiazol-4-yl)methyl ester
Step A: 2,2-Dimethyl-propionic acid (R)-2-[(5-hydroxymethyl-7-nitro-1H-indole-2-carbonyl)-aminol-3-(4-methoxy-benzylsulfanyl)-propyl ester
Step B: 2,2-Dimethyl-propionic acid (R)-2-[(5-chloromethyl-7-nitro-1H-indol-2-yl)-(4,5-dihydro-thiazol-4-yl)methyl ester
Preparation 42: (R)-2-[(5-chloromethyl-7-nitro-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]acetic acid methylester
Preparation 43: 2,2-Dimethyl-propionic acid (R)-2-[5-(2,2-dimethyl-propionyloxymethyl)-7-nitro-1H-indol-2-yl]-4,5--dihydro-thiazol-4-yl-methyl ester
Step A: 2,2-Dimethyl-propionic acid (R)-2-{[5-(2,2-dimethyl-propionyloxymethyl)-7-nitro-1H-indole-2-carbonyl]-amino}-3-(4-methoxy-benzylsulfanyl)-propyl ester
Step B: 2.2-Dimethyl-propionic acid (R)-2-{[5-(2,2-dimethyl-propionyloxymethyl)-7-nitro-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl-methyl ester
Preparation 44: 2,2-Dimethyl-propionic acid (R)-2-{[5-methanesulfonylmethyl-7-nitro-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl-methyl ester
Step A: (5-Methanesulfonylmethyl-7-nitro-1H-indol-2-yl)-carboxylic acid methyl ester
Step B: 2.2-Dimethyl-propionic acid (R)-2-H5-methanesulfonvlmethyl-7-nitro-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl-methyl ester
Preparation 45: (R)-2-[5-methanesulfonylmethyl-7-nitro-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl-acetic acid methyl ester
Preparations 46 to 91
Preparation | R1 | * | n | R2 | Mass [M+H] |
46 | MeO2C- | R | 1 | (pyridin-3-yl)oxy | 412 |
47 | (t-Bu)C(O)O | R | 1 | (pyridin-3-yl)oxy | 454 |
48 | MeO2C- | R | 1 | 4-(methanesulfonyl)phenoxy | 489 |
49 | MeO2C- | R | 1 | methoxy | 347 |
50 | MeO2C- | R | 2 | methoxy | 361 |
51 | MeO2C- | R | 1 | methoxy | 347 |
52 | (i-Pr)O2C- | S | 1 | methyl | 361 |
53 | (t-Bu)C(O)O | R | 1 | methyl | 375 |
54 | EtO2C- | R | 1 | methyl | 347 |
55 | EtO2C- | S | 2 | methyl | 361 |
56 | EtO2C- | R | 2 | methyl | 361 |
57 | EtO2C- | R | 2 | bromo | 412 |
58 | MeO2C- | R | 1 | bromo | 386 |
59 | (t-Bu)C(O)O | R | 1 | bromo | 440 |
60 | (t-Bu)C(O)O | R | 1 | acetylamino | 418 |
61 | MeO2C- | S | 1 | thoxy | 363 |
62 | EtO2C- | R | 2 | ethoxy | 391 |
63 | MeO2C- | R | 1 | ethoxy | 363 |
64 | EtO2C- | R | 1 | chloro | 367 |
65 | (t-Bu)C(O)O | R | 1 | chloro | 395 |
66 | (i-Pr)O2C | S | 1 | chloro | 381 |
67 | MeO2C- | R | 1 | chloro | 353 |
68 | MeO2C- | R | 2 | chloro | 367 |
69 | isobutyl | R | 0 | chloro | 323 |
70 | MeO2C- | R | 1 | phenoxy | 411 |
71 | (i-Pr)O2C- | S | 1 | henoxy | 439 |
72 | MeO2C- | R | 2 | phenoxy | 425 |
73 | MeO2C- | R | 1 | phenylaminomethyl | 424 |
74 | ethyl | R | 0 | fluoro | 293 |
75 | EtO2C- | R | 1 | fluoro | 351 |
76 | EtO2C- | R | 2 | fluoro | 365 |
77 | (t-Bu)C(O)O | R | 1 | fluoro | 379 |
78 | (t-Bu)C(O)O | R | 1 | CH2-(isoindol-1,3-dion-1-yl) | 520 |
79 | MeO2C- | R | 1 | CH2-(isoindol-1,3-dion-1-yl) | 478 |
80 | (t-Bu)C(O)OCH2 | R | 1 | H | 361 |
81 | MeO2C- | R | 1 | H | 319 |
82 | (i-Pr)O2C- | S | 1 | H | 347 |
83 | EtO2C- | R | 2 | H | 347 |
84 | (t-Bu)C(O)OCH2 | S | 1 | H | 361 |
85 | methyl | R | 0 | H | 261 |
86 | ethyl | R | 0 | H | 275 |
87 | MeO2C- | R | 0 | H | 305 |
88 | (t-Bu)C(O)O | R | 2 | H | 375 |
89 | MeO2C- | R | 1 | O(n-Pr) | 363 |
90 | EtO2C- | R | 2 | OCF3 | 417 |
91 | t-BuC(O)O | R | 2 | OCH3 | 391 |
Preparation 92: 2,2-Dimethyl-propionic acid [(R)-2-(5-dimethylaminomethyl-7-nitro-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]methyl ester
Preparation 93: 2,2-Dimethyl-propionic acid {(R)-2-[5-(morpholin-4-yl)methyl-7-nitro-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}methyl ester
Preparation 94: 2,2-Dimethyl-propionic acid {(R)-2-[5-(pyrazol-1-yl)methyl-7-nitro-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}methyl ester
Preparation 95: 2,2-Dimethyl-propionic acid {(R)-2-[5-(1,3-imidazol-1-yl)methyl-7-nitro-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}methyl ester
Preparation 96: 2.2-Dimethyl-propionic acid {(R)-2-[5-(1,2,4-triazol-1-yl)methyl-7-nitro-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}methyl ester
Preparation 97: 2,2-Dimethyl-propionic acid {(R)-2-[5-(pyrrol-1-yl)methyl-7-nitro-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}methyl ester
Preparation 98: [(R)-2-(7-nitro-5-phenoxymethyl-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acetic acid methyl ester
Preparation 99: 2,2-Dimethyl-propionic acid {(R)-2-[7-nitro-5-(phenylamino)methyl-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}methyl ester
Preparation 100 : 2,2-Dimethyl-propionic acid {(R)-2-[7-nitro-5-(pyrrolidin-1-yl)methyl-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}methyl ester
Preparation 101: 2-(4,5-Dihydro-thiazol-2-yl)-7-nitro-1H-indole
Step A: 7-Nitro-1H-indole-2-carboxylic acid
Step B: 7-Nitro-1H-indole-2-carboxylic acid (2-chloro-ethyl)-amide
Step C: 2-(4,5-Dihydro-thiazol-2-yl)-7-nitro-1H-indole
Preparation 102: [(S)-2-(5-chloro-7-nitro-1H-indol-2-yl)-4,5-dihydrooxazol-4-yl]-carboxylic acid isopropyl ester
Step A: (S)-3-amino-4-hydroxy-butyric acid isopropyl ester
Step B: [(S)-3-(5-chloro-7-nitro-1H-indole-2-carbonyl)-amino]-4-hydroxybutyric acid isopropyl ester
Step C: [(S)-3-(5-chloro-7-nitro-1H-indole-2-carbonyl)-amino]-4-methanesulfonyloxy-butyric acid isopropyl ester
Step D: [(S)-2-(5-chloro-7-nitro-1H-indol-2-yl)-4,5-dihydrooxazol-4-yl]-carboxylic acid isopropyl ester
Preparation 103: (1S,2R)-(3-amino-1-benzyl-2-hydroxy-propyl)-carbamic acid t-butyl ester
Step A: (1S,2R)-(3-azido-1-benzyl-2-hydroxy-propyl)-carbamic acid t-butyl ester
Step B: (1S,2R)-(3-amino-1-benzyl-2-hydroxy-propyl)-carbamic acid t-butyl ester
Preparation 104: [(1S, 2R)-1-benzyl-3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-hydroxy-propyllcarbamic acid t-butyl ester
Preparations 105 to 109:
Preparat ion | R1 | R1a | * | ** | n | R3 | Mass [M+H] |
105 | MeO2C | H | S | - | 1 | methyl | 317 |
106 | isobutyl | H | R | - | 0 | Cl | 321 |
107 | H | (S)-Ph-CH2-CH(NH2)- | - | R | 0 | Cl | 384 |
108 | Ph-CH2- |
|
S | R | 1 | Cl | 514 |
109 | H | H | - | - | 0 | H | 231 |
Preparation 110: 2-(Thiazol-2-yl)-7-nitro-1H-indole
Step A: 7-Nitro-1H-indole-2-carbothioic acid amide
Step B: 2-(Thiazol-2_yl)-7-nitro-1H-indole
Preparation 111: 2-(7-Nitro-1H-indol-2-yl)-thiazole-4-carboxylic acid methyl ester
Preparation 112: [2-(7-Nitro-1H-indol-2-yl)-thiazol-4-yl]-methanol
Preparation 113: 2-(5-Methyl-7-nitro-1H-indol-2-yl)-thiazole-4-carboxylic acid ethyl ester
Step A: (5-Methyl-7-nitro-1H-indol-2-yl)carbothioic acid amide
Step B: 2-(5-Methyl-7-nitro-1H-indol-2-yl)-thiazole-4-carboxylic acid ethyl ester
Preparation 114: [2-(5-Methyl-7-nitro-1H-indol-2-yl)-thiazol-4-yl]-methanol
Preparation 115: [5-(7-Nitro-1H-indol-2-yl)-[1,2,4]oxadiazol-3-yl]-acetic acid methyl ester
Step A: 2-(N-hydroxycarbamimidoyl)-acetic acid methyl ester
Step B: 3-(Hydroxyimino)-3-[(7-nitro-1H-indole-2-carbonyl)-amino]-propionic acid methyl ester
Step C: 2-[5-(7-Nitro-1H-indol-2-yl)-[1,2,4]oxadiazol-3-yl]-acetic acid methyl ester
Preparation 116: 2-[5-(7-Nitro-1H-indol-2-yl)-[1,2,4]oxadiazol-3-yl]-ethanol
Preparation 117: 5-Methyl-7-nitro-2-[1,3,4]oxadiazol-2-yl-1H-indole
Example 1: Cyclopentyl-[2-(4,5-dihydro-1,3-thiazol-2-yl)-1H-indol-7-yl]-amine
Step A: [2-(4,5-Dihydro-1,3-thiazol-2-yl)-1H-indol-7-yl]-amine
Step B: Cyclopentyl-[2-(4,5-dihydro-1,3-thiazol-2-yl)-1H-indol-7-yl]-amine
Example 2: [(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-4-yl]-methanol
Step A: 2,2-Dimethyl-propionic acid [(R)-2-(7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl] methyl ester
Step B: [(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-4-yl]-methanol
Example 3: [(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acetic acid methyl ester
Example 4: [(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acetic acid
Example 5: 2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol
Example 6: (R)-2-[7-cyclopentylamino-5-(hydroxymethyl)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl-methanol
Step A: 2,2-Dimethyl-propionic acid (R)-2-[7-cyclopentylamino-5-(2,2-dimethyl-propionyloxymethyl)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl-methyl ester
Step B: (R)-2-[7-cyclopentylamino-5-(hydroxymethyl)-1H-indol-2-yl]-4,5 dihydro-thiazol-4-yl-methanol
Reference Example 7: [2-(4,5-Dihydro-thiazol-2-yl)-1H-indol-7-yl]-piperidin-4-yl-amine
Step A: [2-(4,5-Dihydro-thiazol-2-yl)-1H-indol-7-yl]-(1-BOC-piperidin-4-yl)-amine
Step B: [2-(4,5-Dihydro-thiazol-2-yl)-1H-indol-7-yl]-piperidin-4-yl-amine
Examples 8 to 117:
Example | R1 | * | n | R2 | R3 | R4 |
H1 NMR data | ||||||
Reference Example 8 | carboxyl | R | 1 | methyl | H | (THP-4-yl)methyl |
(400MHz, CDCl3); δ 11.54 (brs, 1H), 7.11 (s, 1H), 6.80 (s, 1H), 6.22 (s, 1H), 5.29 (m, 1H), 3.92 (m, 2H), 3.68 (m, 1H), 3.35 (m, 2H), 3.21-3.04 (m, 3H), 2.84-2.52 (m, 2H), 2.32 (s, 3H), 1.90 (m, 1H), 1.74 (m, 2H),1.35 (m, 2H) | ||||||
Reference Example 9 | carboxyl | S | 1 | methyl | H | 1-(trifluoroacetyl)piperidin-4-yl |
(400MHz, CDCl3); δ 11.94 (brs,1H), 6.98 (s, 1H), 6.78 (s, 1H), 6.25 (s, 1H), 5.33 (m, 1H), 4.13 (m, 1H), 3.76-3.68 (m, 5H), 3.47-3.41 (m, 3H), 2.74-2.63 (m, 2H), 2.36 (s, 3H), 2.04 (m, 2H),1.56 (m, 2H) | ||||||
Reference Example 10 | carboxyl | S | 1 | H | H | (THP-2-yl)methyl |
(400MHz, CDCl3); δ 11.68 (brs, 1H), 7.06-6.98 (m, 3H), 6.45 (s, 1H), 5.32 (m, 1H), 3.96 (m, 1H), 3.77-3.61 (m, 2H), 3.43 (m, 1H), 3.28-3.21 (m, 3H), 2.80 (m, 1H), 2.65 (m, 1H), 1.83 (m, 1H), 1.71 (m, 1H), 1.62-1.42 (m, 4H) | ||||||
Reference Example 11 | carboxyl | S | H | H | THP-4- yl | |
(400MHz, CDCl3); δ 11.87 (brs, 1H), 7.15 (s, 1H), 7.03 (m, 2H), 6.50 (m, 1H), 5.39 (m, 1H), 4.06 (m, 2H), 3.80-3.62 (m, 2H), 3.57 (m, 2H), 3.29 (m, 1H), 2.83 (m, 1H), 2.69 (m,1H), 2.11 (m, 2H), 1.64 (m, 2H) | ||||||
Reference Example 12 | carboxyl | S | 1 | H | H | (THP-4-yl)methyl |
(400MHz, CDCl3); δ 11.89 (brs, 1H), 7.13 (s, 1H), 7.04 (m, 2H), 6.44 (m 1H), 5.39 (m, 1H), 3.98 (m, 2H), 3.77 (m, 1H), 3.41 (m, 2H), 3.25 (m, 1H), 3.13 (m, 2H), 2.78 (m, 1H), 2.64 (m, 1H), 2.00 (m, 1H), 1.79 (m, 2H),1.44 (m, 2H) | ||||||
Reference Example 13 | carboxyl | S | 1 | methyl | H | 1-acetyl-pyrrrolidin-3-yl |
(400MHz, CDCl3); δ 10.13 (brs, 1H), 6.93 (s, 1H), 6.82 (s, 1H), 6.38 (s, 1H), 5.09 (m, 1H), 4.16 (m, 1H), 3.67 (m, 2H), 3.52 (m, 2H), 3.38 (m, 1H), 3.25 (m, 1H), 2.91 (m, 1H), 2.66 (m, 1H), 2.48 (s, 3H), 2.23 (m, 1H), 2.00 (m, 1H) | ||||||
14 | carboxyl | S | 1 | H | H | c-Pen |
(400MHz, CDCl3); δ 11.74 (brs, 1H), 7.06 (s, 1H), 6.99 (m, 2H), 6.45 (s, 1H), 5.48 (m, 1H), 3.90 (m, 1H), 3.71 (m, 1H), 3.23 (m, 1H), 2.75 (m, 1H), 2.67 (m, 1H), 2.04 (m, 2H), 1.75 (m, 2H), 1.61-1.48 (m, 4H) | ||||||
Reference Example 15 | carboxyl | R | 1 | phenoxy | H | (THP-4-yl)methyl |
(400MHz, CDCl3) δ 11.96 (brs,1H), 7.7.30 (m, 2H), 7.03 (m, 4H), 6.60 (s, 1H), 6.20 (s, 1H),5.3(m, 1H), 3.93(m, 1H3.73 (m, 1H), 3.35 (m; 2H), 3.23 (m, 1H), 3.06(m,2H2.72 (m, 1H),2.62 (m,1H), 1.92 (m, 1H), 1.73 (m, 2H), 1.40m, 2H) | ||||||
Reference Example 16 | carboxyl | S | 1 | phenoxy | H | THP-4-yl |
(400MHz, CDCl3), δ 11.95 (brs,1H), 7.28 (m, 2H), 7.06-6.96 (m, 4H), 6.58 (s, 1H), 6.24 (s,H)5.33 (m, 1H),98 (m,2H), 3.75 (m, 1H), 3.58-3.47 (m, 3H), 2.23 (m,1H),2.72.78-2.62 (m, 2H), 2.0404 (m,2H), 1.26 (m, 2H) | ||||||
17 | carboxyl | S | 2 | methyl | H | 4,4-difluorocyclohexane |
(400MHz,CDCl3δ 11.94 (brs,1H),), 7.00(s, 1H); 6.78 (s, 1H), 6.26 (s, 1H), 5.35 (m, 1H),3.71(m ,1H), 3.63 (m, 1H),), 3.22(m, 1H), 2.75 (m, 1H), 2.62 (m, 1H), 2.37 (s,25(m, 1H), 2.09-1.73(m,(m, 7H) | ||||||
Reference Example 18 | carboxyl | S | 1 | chloro | H | (THP-4-yl)methyl |
(400MHz,DMSO-d5); δ 11.61(br s,1H)6.85(s, 1H), 6.75(s, 1H), 6.21(s, 1H). 6.15(s, 1H),4911H), 3.90(m,H). 3.3.65(m, 1H). 3.41~3.20(m, 4H), 3.05(m, 2H),2.6(m2H), 1.88(m, 1H),), 1.761.76(m, 2H), 1.31(m, 2H), 1.09(m, 1H) | ||||||
19 | carboxyl | S | 1 | methyl | H | cyclobutyl |
(400MHz,CICl3); δ 11.21(br s,1H),6.66(s, 1H), 6.61(s, 1H), 6.00(s, 1H), 4.89(br s,1H)3.93.95(m, 1H), 3.63(m,,1H),3.35(m, 2H), 2.67(m, 2H), 2.50(s, 3H), 2.42(m,804H) | ||||||
Reference Example 20 | carboxyl | S | 1 | methyl | H | tetrahydrofuran-3-yl |
(400MHz,CD11.829d, 1H),6.95(s1H), 6.79(s, 1H), 6.20(d, 1H), 5.30(br s, 1H),5(4.15(m, 1H),4.05~3.75(m,5H),3.66(m, 1H), 3.19(s, 1H), 2.79~2.61(m, 2H), 2.37(s, 3H), 2.23(m, 1H), 1.98(m, 1H) | ||||||
21 | carboxyl | S | 1 | methyl | H | cyclopropylmethyl |
(400MHz, CDCl3/MeOH-d4); δ 11.24(br s, 1H), 6.84(s, 1H), 6.77(s, 1H), 6.25(s, 1H), 5.05(m, 1H), 3.56(m, 1H), 3.15(m, 2H), 3.03(m, 2H), 2.78(m, 1H), 2.63(m, 1H), 2.34(s, 3H), 1.23(m, 1H), 1.18(m, 1H), 0.52(m, 2H), 0.24(m, 2H) | ||||||
Reference Example 22 | carboxyl | S | 1 | methyl | H | (THP-4-yl)methyl |
(400MHz, CDCl3); δ 11.92(br S, 1H), 6.98(s, 1H), 6.77(s, 1H), 6.22(s, 1H), 6.29(br s, 1H), 3.96(m, 2H), 3.70(m, 1H), 3.37(m, 2H), 3.18(m, 1H), 3.08(m, 2H), 2.729m, 1H), 2.56(m, 1H), 2.37(s, 3H), 1.91(m, 1H), 1.75(m, 2H), 1.41(m, 2H) | ||||||
23 | carboxyl | S | 1 | methyl | H | (c-Pen)methyl |
(400MHz, DMSO-d6); δ 11.35(br s, 1H), 6.67(s, 1H), 6.61(s, 1H), 6.09(s, 1H), 5.81(br s, 1H), 4.90(m, 1H), 3.64(m, 1H), 3.21(m, 1H), 3.05(m, 2H), 2.77~2.69(m, 2H), 2.28(s, 3H), s.23(m, 1H), 1.85(m, 2H), 1.65~1.58(m, 4H), 1.32(m, 2H) | ||||||
Reference Example 24 | HO- | S | 2 | methyl | H | THP-4-yl |
(400MHz, CDCl3); δ 10.37(br s, 1H), 6.84(s, 1H), 6.82(s, 1H), 6.32(s, 1H), 4.64(m, 1H), 4.00(m, 4H), 3.63~3.51(m, 4H), 3.11(t, 1H), 2.38(s, 3H), 2.05(m, 4H), 1.51(m,2H) | ||||||
Reference Example 25 | carboxyl | S | 1 | methyl | H | THP-4-yl |
(400MHz, DMSO-d6); δ 11.77(br s, 1H), 6,98(sm 2H), 6.67(s, 1H), 4.95(m, 1H), 4.02(m, 2H), 3.72(m, 2H), 3.42~3.29(m, 3H), 2.86~2.69(m, 2H), 2.50(s, 1H), 1.94(m,2H), 162(m, 2H) | ||||||
26 | carboxyl | S | 1 | methyl | H | c-Pen |
(400MHz, DMSO-db); δ 11.88(br s, !H), b7.09(s, 1H), 7.04(s, 1H), 6.74(s, 1H), 4.94(m, 1H), 3.98(m, 1H), 3.73(m, 1H), 3.47(m, 1H), 2.87~2.70(m, 2H), 2.51(s, 3H), 1.93(m, 2H), 1.76~1.56(m, 6H) | ||||||
Reference Example 27 | H | - | 0 | H | H | (thiophen-3-yl)methyl |
(400MHz, CDCl3); δ 9.67(s, 1H), 7.32(dd, 1H), 7.21(m, 1H), 7.13(d, J=8.0Hz, 1H), 7.07(d, J= 5.2Hz,, 1H), 7.02(t, J=8.0Hz, 1H), 6.91(s, 1H), 6.56(d, J=7.6Hz, 1H), 4.42(s, 2H), 4.36(m, 2H), 3.36(m, 2H) | ||||||
Reference Example 28 | H | - | 0 | H | H | tetrahydrofuran-3-yl |
(400MHz, CDCl3); δ 10.36(s, 1H), 7.10(d, J=8.0Hz, 1H), 7.00(t, J= 8.0Hz, 1H), 6.99(s, 1H), 6.45(d, J=7.6Hz, 1H), 4.41(m, 2H), 4.18(s, 1H), 3.98~3.73(m, 4H), 3.47(m, 2H), 2.28(m, 1H), 1.90(m, 1H) | ||||||
29 | HO- | R | 1 | H | H | cyclohexyl |
(500MHz, CDCl3); δ 11.17~11.08(m, 1H), 7.09(m, 1H), 6.99(t, 1H), 6.96(s, 1H), 6.52(m, 1H), 4.72(m, 1H), 4.04(m, 1H), 3.75(m, 1H), 3.65(m, 1H), 3.51(m, 1H), 3.40(m, 1H), 1.90(m, 2H), 1.60~1.49(m, 4H), 1.41~1.24(m, 2H) | ||||||
Reference Example 30 | carboxyl | R | 2 | H | H | THP-4-yl |
(400MHz, DMSO-d6); δ 12.42(br s,1H), 11.34(s, 1H), 6.80(d, 1H), 6.72(s, 1H), 6.33(d, 1H), 5.79(d, 1H), 4.86(q, 1H), 3.88(m, 2H), 3.60-3.52(m, 2H), 3.42(t, 2H), 3.17(m, 1H), 2.74(m, 1H), 2.59(m, 1H),1.94(m, 2H), 1.39(m, 2H) | ||||||
Reference Example 31 | HO- | R | 1 | chloro | H | isopropyl |
(400MHz, CDCl3); δ 10.89(br s, 1H), 7.00(s, 1H), 6.83(s, 1H), 6.43(s, 1H), 4.75(m, 1H), 4.04(dd, 1H), 3.71(dd, 1H), 3.61(m, 1H), 3.43(dd, 1H), 1.09(t, 6H) | ||||||
Reference Example 32 | methyl | R | 0 | H | H | THP-4-yl |
(400MHz, CDCl3); δ 11.13(br s, 1H), 7.08~6.99(m, 3H), 6.53(d, 1H), 4,76(m, 1H), 4.09(m, 2H), 3.72(m, 1H), 3.63(m, 3H), 3.12(m, 1H), 2.13(m, 2H), 1.68(m, 2H), 1.48(d, 3H) | ||||||
33 | HO- | R | 1 | (morpholin-4-yl)methyl | H | c-Pen |
(400MHz, CDCl3); δ 10.77(br s, 1H), 7.06(s, 1H), 6.95(s, 1H), 6.62(s, 1H), 4.80(m, 1H), 4.11(m, 1H), 3.99(m, 2H), 3.76(m, 1H), 3.75(m, 4H), 3.51(s, 2H), 3.45(m, 5H), 2.51(br s, 4H), 2.00(m, 2H), 1.45(m, 2H) | ||||||
34 | HO- | R | 1 | (dimethylamino )methyl | H | c-Pen |
(400MHz, CDCl3); δ 10.86(br s, 1H), 6.96(s, 1H), 6.88(s, 1H), 6.51(s, 1H), 4.75(m, 1H), 4.37(m, 2H), 3.85(m, 1H), 3.71(m, 1H), 3.50(s, 2H), 3.42(m, 2H), 2.27(s, 6H), 1.96(m, 2H), 1.59(m, 4H), 1.39(m, 2H) | ||||||
35 | HO- | R | 1 | (pyrrol-3-yl)methyl | H | c-Pen |
(400MHz, CDCl3); δ 11.04(1H, br), 7.85(1H, br), 6.90~6.85(2H, m), 6.62(1H, s), 6.36(1H, s), 6.13(1H, m), 6.01(1H, s), 4.77~4.67(1H, m), 4.08~4.01(1H, m), 3.99(2H, s), 3.78~3.65(2H, m), 3.52~3.38(2H, m), 1.98~1.85(2H, m), 1.65~1.47(4H, m), 1.42~1.33(1H, m), 1.33~1.26(1H, m) | ||||||
36 | HO- | R | 1 | (1,3-imidazol-1-yl)methyl | H | c-Pen |
(400MHz, CDCl3); δ 11.10(1H, br), 8.21(1H, s), 7.25(1H, s), 7.23(1H, s), 6.87(3H, br), 6.16(1H, s), 5.05(2H, s), 4.81~4.73(1H, m), 4.00~3.93(1H, m), 3.79~1.73(1H, m), 3.73~3.67(1H, m), 3.49~3.37(2H, m), 1.98~1.88(2H, m), 1.66~1.53(4H, m), 1.43~1.37(2H, m) | ||||||
37 | HO- | R | 1 | (pyrazol-1-yl)methyl | H | c-Pen |
(500MHz, CDCl3); δ 11.11(1H, br), 7.52(1H, d, J=1.85Hz), 7.34(1H, d, J=2.45Hz), 6.93(1H, s), 6.88(1H, s), 6.34(1H, s), 6.22(1H, m), 5.31(2H, s), 4.75~4.67(1H, m), 4.02~3.95(1H, m), 3.70~3.61(2H, m), 3.47~3.38(2H, m), 1.92~1.81(2H, m), 1.60~1.46(4H, m), 1.33~1.20(2H, m) | ||||||
38 | HO- | R | 1 | acetylamino H | c-Pen | |
(400MHz, CDCl3); δ 10.71(br s, 1H), 7.26(s, 1H), 7.23(s, 1H), 6.88(s, 1H), 4.77(m, 1H), 4.02(m, 1H), 3.80(m, 1H), 3.73(m, 1H), 3.47(m, 2H), 2.20(s, 3H), 2.04(m, 2H), 1.60(m, 4H), 1.44(m, 2H) | ||||||
39 | carboxyl | R | 1 | phenoxymethyl | H | c-Pen |
(500MHz, CDCl3); δ 11.79(1H, br), 7.29~7.26(2H, m), 7.03~7.00(3H, m), 6.99(1H, s), 6.93(1H, m), 6.48(1H, m), 5.39~5.30(1H, m), 5.07(2H, s), 3.94~3.86(1H, m), 3.75~3.68(1H, m), 3.24~3.18(1H, m), 2.78~2.70(1H, m), 2.68~2.61(1H, m), 2.05~1.96(2H, m), 1.79~1.70(2H, m), 1.66~1.56(4H, m) | ||||||
40 | MeO2C- | R | 1 | (pyrrolidin-1-yl)methyl | H | c-Pen |
(500MHz, CDCl3); δ 10.13(1H, br), 6.97(1H, s), 6.88(1H, s), 6.73(1H, s), 5.05~4.95(1H, m), 4.04(2H, s), 3.73(3H, s), 3.70~3.60(1H, m), 3.49(4H, s), 3.25~3.15(1H, m), 3.10~2.95(1H, m), 2.90~2.85(1H, m), 2.71~2.65(1H, m)2.15~1.53(12H, m) | ||||||
41 | isobutyl | R | 0 | chloro | H | c-Pen |
(500MHz, CDCl3); δ 10.68(br s, 1H), 7.00(s, 1H), 6.89(s, 1H), 6.42(s, 1H), 4.54(t, 1H), 4.40(m, 1H), 4.07(t, 1H), 3.84(m, 1H), 2.04(m, 2H), 1.80~1.32(m, 9H), 0.89(d, 3H), 0.83 (d, 3H) | ||||||
42 | EtO2C- | R | 2 | H | H | c-Pen |
(400MHz, CDCl3); δ 9.79(br s, 1H), 7.05(m, 1H), 6.96(m, 1H), 6.91(s, 1H), 6.52(d, J=8Hz, 1H), 4.72(m, 1H), 4.08(m, 2H), 3.90(m, 1H), 3.55(t, 1H), 3.12(t, 1H), 2.52(m, 2H), 2.04(m, 4H), 1.63(m, 2H), 1.53(m, 4H), 1.28(m, 1H), 1.20(t, 3H) | ||||||
Reference Example 43 | HO- | R | 1 | H | H | (3R)-1-acetylpyrrolidin-3-yl |
(500MHz, CDCl3); δ 10.86(br s, 1H), 7.03(m, 1H), 7.00(m, 1H), 6.88(d, 1H), 6.43(m, 1H), 4.74(m, 1H), 4.25(m, 1H), 4.17(m, 1H), 3.95(m, 1H), 3.69(m, 2H), 3.62(m, 1H), 3.51~3.42(m, 5H), 3.25(m,1H), 2.04(m, 2H) | ||||||
44 | ethyl | R | 0 | fluoro | H | c-Pen |
(500MHz, CDCl3); δ 11.22(br s,1H), 6.88(s, 1H), 6.63(d, 1H), 4.65(m, 1H), 3.99(br s, 1H), 3.75(m, 1H), 3.53(m, 1H), 3.117(m, 1H), 2.02~1.94(m, 2H), 1.77(m, 1H), 1.63(m, 5H), 1.44(m, 1H), 1.28(m, 1H), 0.94(m, 3H) | ||||||
45 | HO- | R | 1 | fluoro | Me | c-Pen |
(500MHz, CDCl3); δ 10.28(br s, 1H), 6.92(d, 1H), 6.70(d, 1H), 6.59(s, 1H), 4.71(m, 1H), 4.22(dd, 1H), 3.75(dd, 1H), 3.69(m,1 H), 3.59(t, 1H),3.35(t, 1H), 2.68(s, 3H), 1.82(m, 1H), 1.72(m, 1H), 1.62~1.40(m, 6H) | ||||||
46 | MeO2C- | S | 1 | ethoxy | H | c-Pen |
(400MHz, CDCl3); δ 10.66(br s, 1H), 6.82(s, 1H), 6.41(s, 1H), 6.17(s, 1H), 5.08(m, 1H), 4.01(m, 2H), 3.80(m, 1H), 3.67(m, 1H), 3.49(s, 3H), 3.20(dd, 1H), 2.85(dd, 1H), 2.65(dd, 1H), 2.02(m, 1H), 1.66~1.53(m, 4H), 1.45-1.33(m, 5H) | ||||||
47 | carboxyl | S | 1 | ethoxy | H | c-Pen |
NMR (400MHz, CDCl3); δ 11.99(br s, 1H), 6.95(s, 1H), 6.34(s, 1H), 6.11(s, 1H), 5.33(m, 1H), 4.04(m, 2H), 3.83(m, 1H), 3.69(m, 1H), 3.18(d, 1H), 2.73(m, 1H), 2.59(m, 1H), 2.00(m, 2H), 1.73(m, 2H), 1.59(m, 4H), 1.43(m, 3H) | ||||||
48 | HO- | S | 2 | ethoxy | H | c-Pen |
(400MHz, CDCl3); δ 10.64(br s, 1H), 6.82(s, 1H), 6.39(d, 1H), 6.15(d, 1H), 4.69(br s, 1H), 4.60(m, 1H), 4.06~3.84(m, 5H), 3.54(m, 1H), 3.10(m, 1H), 2.08~1.94(m, 4H), 1.70(m, 2H), 1.58(m, 4H), 1.40(m, 3H) | ||||||
49 | EtO2C- | R | 0 | methyl | H | c-Pen |
(400MHz, CDCl3); δ 9.74(br s, 1H), 6.85(d, J=4Hz, 2H), 6.37(s, 1H), 5.33(t, 1H), 4.23(m, 2H), 3.87(m, 1H), 3.71(m, 2H), 2.39(s, 3H), 2.03(m, 2h), 1.68(m, 2H), 1.61(m, 2H), 1.47(m, 2h), 1.26(t, 3H) | ||||||
50 | carboxyl | S | 1 | phenoxy | H | c-Pen |
(400MHz, DMSO-d6,Na salt); δ 11.85(br s, 1H), 7.31 (t, 2H), 7.01(t, 1H), 6.93(d, J=8Hz, 2H), 6.64(s, 1H), 6.48(d, J=4Hz, 1H), 6.39(s, 1H), 5.97(s, 1H), 4.93(m, 1H), 3.75(m, 1H), 3.55(t, 1H), 3.20(q, 1H), 2.62(dd, 1H), 2.15(q, 1H), 1.90(m, 2H), 1.72(m, 2H), 1.60(m, 4H) | ||||||
Reference Example 51 | HO- | R | 1 | H | H | THP-4-yl |
(400MHz, CDCl3); δ 10.91(br s, 1H), 7.01~6.91(m, 3H), 6.48(d, J=7.2Hz, 1H), 4.86(m, 1H), 4.34(m 2H), 4.00(m, 2H), 3.61(m, 1H), 3.54(m, 3H), 3.31(m, 1H), 2_OS(m, 2H), 1.55(m, 2H), 1.16(s, 9H) | ||||||
Reference Example 52 | HO- | R | 1 | H | H | THF-3-yl |
(500MHz, CDCl3); δ 10.58(br s, 1H), 7.14(d, J=7.95Hz, 1H), 7.00(m, 1H), 6.94(m, 1H), 6.48(d, J=7.35Hz, 1H), 4.79(m, 1H), 4.15~3.95((m, 3H), 3.90~3.65(m, 4H), 3.50~3.39(m, 2H), 2.20(m, 1H), 1.83(m, 1H) | ||||||
Reference Example 53 | HO- | R | 1 | H | H | 1-(methanesulfonyl)pyrrolidin-3-yl |
(500MHz, CDCl3); δ 10.50(br s, 1H), 7.15(d, J=7.95Hz, 1H), 7.00(dd, 1H), 6.93(s, 1H), 6.46(d, J=7.35Hz, 1H), 4.77(m, 1H), 4.18(m, 1H), 4.08(dd, 1H), 3.75(dd, 1H), 3.59~3.36(m, 6H), 3.48(s, 3H), 2.27(m,1H), 1.95(m, 1H) | ||||||
54 | HO- | R | 1 | fluoro | H | c-Pen |
(400MHz, CDCl3); δ 10.73(br s, 1H), 6.91(s, 1H), 6.72(m, 1H), 6.33(m, 1H), 4.78(m, 1H), 4.12(m, 1H), 3.97(br s, 1H), 3.79(m, 1H), 3.75(m, 1H), 3.49(m, 2H), 2.01(m, 2H), 1.62(m, 4H), 1.41(m, 2H) | ||||||
Reference Example 55 | HO- | R | 1 | fluoro | H | THP-4-yl |
(400MHz, CDCl3); δ 10.45(br s, 1H), 6.90(s, 1H), 6.75(m, 1H), 6.34(m, 1H), 4.82(m, 1H), 4.12(m, 1H), 4.01(m, 2H), 3.94(m, 1H), 3.78(m, 1H), 3.54~3.43(m, 5H), 2.03(m, 2H), 1.50(m, 2H) | ||||||
56 | HO- | R | 2 | chloro | H | c-Pen |
(500MHz, CDCl3); δ 10.53(br s, 1H), 7.24(s, 1H), 6.84(d, 1H), 6.45(s, 1H), 4.74(m, 1H), 4.06(m, 1H), 3.81(m, 1H), 3.71(m, 1H), 3.45(dd, 2H), 1.99(m, 2H), 1.60(m, 4H), 1.37(m, 2H) | ||||||
57 | HO- | R | 1 | chloro | H |
|
(400MHz, CDCl3); δ 10.87(br s, 1H), 7.01(s, 1H), 6.89(s, 1H), 6.40(s, 1H), 4.80(m, 1H), 4.10(m, 1H), 3.80(m, 1H), 3.50(m, 2H), 3.32(m, 1H), 2.76(m, 4H), 2.29(m, 2H), 1.56 (m, 2H) | ||||||
58 | HO- | R | 1 | bromo | H | c-Pen |
(400MHz, CDCl3); δ 10.59(br s, 1H), 7.23(s, 1H), 6.88(s, 1H), 6.64(d, 1H), 4.77(m, 1H), 4.14(m, 1H), 3.82(m, 1H), 3.76(m, 1H), 3.49(dd, 2H), 2.04(m, 2H), 1.65(m, 4H), 1.41(m, 2H) | ||||||
Reference Example 59 | HO- | R | 1 | bromo | H | THP-4-yl |
(400MHz, CDCl3); δ 10.53(br s, 1H), 7.25(s, 1H), 6.87(s, 1H), 6.63(d, 1H), 4.80(m, 1H), 4.14(m, 1H), 4.03(m, 2H), 3.79(m, 1H), 3.56-3.3.44(m, 4H), 2.02(m, 2H), 1.45(m, 2H) | ||||||
60 | HO- | R | 1 | methoxy | H | c-Pen |
(500MHz, DMSO-d6); δ 11.23(br s, 1H), 6.60(s, 1H), 6.23(s, 1H), 5.89(m, 1H), 5.84(m, 1H), 4.96(m, 1H), 4.65(m, 1H), 3.77(m, 1H), 3.70(m, 1H), 3.45(m, 1H), 3.33(m, 1H), 3.29(s, 3H), 1.91(m, 2H), 1.67(m, 2H), 1.53(m, 4H) | ||||||
61 | HO- | R | 1 | (pyridin-3-yl)oxy | H | c-Pen |
(400MHz, CDCl3); δ 11.16(br s, 1H), 8.42(d, 1H), 8.28(m, 1H), 7.30(m, 1H), 7.22(m, 1H), 6.88(s, 1H), 6.67(d, 1H), 6.28(d, 1H), 4.83(m, 1H), 4.02(m, 1H), 3.75(m, 2H), 3.46(m, 2m, 1.97(m, 2H), 1.63(m, 4H), 1.43(m, 2H) | ||||||
Reference Example 62 | HO- | R | 1 | (pyridin-3-yl)oxy | H | THP-4-yl |
(400MHz, CDCl3); δ 10.96(br s, 1H), 8.36(d, J=2.4Hz; 1H), 8.26(m, 1H), 7.27(m, 1H), 7.19(m, 1H), 6.83(s, 1H), 6.63(d, J=1.6Hz, 1H), 6.24(d, J=1.6Hz, 1H), 4.81(m, 1H), 4.01~3.94(m, 3H), 3.75(m, 1H), 3.47(s, 3H), 3.48~3.29(m, 5H), 1.93(m, 2H), 1.52(m, 2H) | ||||||
63 | HO- | R | 1 | methanesulfony methyl | H | c-Pen |
(500MHz, CDCl3); δ 11.10(brs, 1H), 7.01(s, 1H), 6.88(m, 1H), 6.49(s, 1H), 4.76(m, 1H), 426(s, 2H), 3.99(m, 1H), 3.79(m, 1H), 3.68(m, 1H), 3.43(m, 2H), 2.73(s, 3H), 1.96(m, 2H), 1.57(m, 4H), 1.35(m, 2H) | ||||||
64 | HO- | R | 1 | (isoindol-1,3-dion-2-yl)methyl | H | c-Pen |
(500MHz, DMSO-d6); δ 11.30(brs, 1H), 8.83(brs, 1H), 7.69(m, 1H), 7.51(m, 1H), 7.44(m, 2H), 6.78(s, 1H), 6.67(d, 1H), 628(s, 1H), 5.81(s, 1H), 4.96(brs, 1H), 4.67(m, 1H), 4.37(d, 2H), 3.83(m, 1H), 3.70(m, 1H), 3.52(m, 1H), 3.46(m, 1H), 1,94(m, 2H), 1.68(m, 2H), 1.54(m, 4H) | ||||||
Reference Example 65 | MeO2C- | R | 1 | chloro | H | THP-4-yl |
(400MHz, DMSO-d6); δ 11.52(s, 1H), 6.81 (s, 1H), 6.71(s, 1H), 6.28(s, 1H), 6.07(d, 1H), 4.90(m, 1H), 3.86(m, 2H), 3.64(s, 3H), 3.62(m, 2H), 3.44(t, 2H), 2.82-2.71 (m, 2H), 1.94(m, 2H), 1.40(m, 2H) | ||||||
Reference Example 66 | carboxyl | R | 1 | chloro | H | THP-4-yl |
(400MHz, DMSO-d6); δ 12.43(br s, 1H), 11.53(s, 1H), 6.81(s, 1H), 6.71(s, 1H), 6.28(s, 1H), 6.06(d, 1H), 4.87(m, 1H), 3.87(m, 2H), 3.62(m, 2H), 3.44(t, 2H), 3:19(m, 1H), 3.74(m, 1H), 2.63(m, 1H), 1.94(m,. 2H), 1.41(m, 2H) | ||||||
Reference Example 67 | HO- | R | 2 | chloro | H | THP-4-yl |
(400MHz, DMSO-d6); δ 11.48(s, 1H), 6.81(s, 1H), 6.68(s, 1H), 6.28(s, 1H), 6.05(d, 1H), 4.66(q, 1H), 4,54(t, 1H), 3.87(m, 2H), 3.61-3.54(m, 3H), 3.44(t, 2H), 3.15(m, 1H), 1.99-1.93(m, 3H), 1.73(m, 1H), 1.40(m, 2H), 1.20(m, 1H) | ||||||
68 | carboxyl | R | 1 | bromo | H | c-Pen |
(400MHz, CDCl3); δ 12.50(br s, 1H), 7.10(sm 1H), 7.06(s, 1H), 6.56(s, 1H), 5.31(m, 1H), 3.89(m, 2H), 3.40(m, 1H), 2.99(m, 1H), 2.83(m, 1H), 2.08(m, 2H), 1.86(m, 2H), 1.66(m, 4H) | ||||||
69 | HO- | R | 2 | bromo | H | c-Pen |
(400MHz, CDCl3); δ 10.42(br s, 1H), 7.18(s, 1H), 6.87(s, 1H), 6.59(d, 1H), 4.67(m, 2H), 4.02(m, 2H), 3.91(m, 1H), 3.63(m, 1H), 3.16(t, 1H), 2.10(m, 4H), 1.74(m, 2H), 1.4(m, 4H) | ||||||
Reference Example 70 | HO- | R | 2 | bromo | H | THP-4-yl |
(400MHz, CDCl3); δ 10.50(br s, 1H), 7.19(s, 1H), 6.89(s, 1H), 6.59(d, 1H), 4.67(m, 2H), 4.05(m, 4H), 3.63(m, 4H), 3.18(t, 1H), 2.12(m, 4H), 1.64(m, 4H) | ||||||
71 | carboxyl | R | 1 | fluoro | H | c-Pen |
(400MHz, CDCl3); δ 11.09(br s, 1H), 6.73(s, 1H), 6.45(dd, 1H), 6.07(dd, 1H), 4.98(m, 1H), 3.79(m, 1H), 3.59(m, 1H), 3.16(m, 1H), 2.79(m, 1H), 2.60(m, 1H), 1.96(m, 2H), 1.71(m, 2H), 1.58(m, 4H) | ||||||
72 | EtO2C- | R | 1 | fluoro | H | c-Pen |
(400MHz, CDCl3); δ 10.71(br s, 1H), 6.86(s, 1H), 6.64(dd, 1H), 6.23(dd, 1H), 5.07(m, 1H), 3.99(q, 2H), 3.91(m, 1H), 3.76(m, 1H), 3.64(m, 1H), 3.22(m, 1H), 2.88(m, 1H), 2.65(m, 1H), 2.00(m, 2H), 1.63(m, 4H), 1.40(m, 2H), 1.12(t, 3H) | ||||||
73 | HO- | R | 2 | fluoro | H | c-Pen |
(400MHz, CDCl3); δ 10.90(br s, 1H), 6.91(s, 1H), 6.65(dd, 1H), 6.26(dd, 1H), 4.68(m, 1H), 4.08(m, 2H), 3.88(m, 1H), 3.62(m, 1H), 3.15(t, 1H), 2.10(m, 4H), 1.74(m, 2H), 1.62(m, 4H) | ||||||
Reference Example 74 | carboxyl | R | 1 | fluoro | H | THP-4-yl |
(400MHz, DMSO-d6); δ 11.45(s, 1H), 6.75(d, 1H), 6.22(dd, 1H), 6.16(d, J=6.8Hz, 1H), 4.91(m, 1H), 3.88(m, 2H), 3.66(m, 1H), 3.61 (m, 1H), 3.48(m, 2H), 3.22(m, 1H), 2.80(m, 1H), 2.65(m, 1H), 2.99(m, 2H), 1.40(m, 2H) | ||||||
75 | carboxyl | R | 1 | H | H | c-Pen |
(400MHz, CDCl3); δ 11.77(br s, 1H), 7.04(d, 1H), 6.97(m, 2H), 6.43(d, 1H), 5.34(m, 1H), 3.88(m, 1H), 3.69(m, 1H), 3.19(m, 1H), 2.72(m, 1H), 2.60(m, 1H), 2.01 (m, 2H), 1.74(m, 2H), 1.59(m, 4H) | ||||||
76 | EtO2C- | R | 1 | H | H | c-Pen |
(400MHz, CDCl3); δ 10.12(br s, 1H), 7.05(m, 1H), 6.99(m, 1H), 6.91(d, 1H), 6.51(d, 1H), 5.07(m, 1H), 4.09(q, 2H), 3.87(m, 1H), 3.65(m, 1H), 3.21(m, 1H), 2.86(m, 1H), 2.65(m, 1H), 2.01.(m, 2H), 1.74(m, 2H), 1.62(m, 4H), 1.46(m, 2H), 1.81(t, 3H) | ||||||
77 | HO- | R | 2 | H | H | c-Pen |
(400MHz, DMSO-d6); δ 11.28(s, 1H), 6.77-6.74(m, 2H), 6.69(s, 1H), 6.25(d, 1H), 5.78(d, 1H), 4.65(q, 1H), 4.53(t, 1H), 3.82(m, 1H), 3.60(m, 2H), 3.51(m, 1H), 3.11(m, 1H), 1.99-1.91(m, 3H), 1.75-1.67(m, 3H), 1.56-1.54(m, 4H) | ||||||
Reference Example 78 | carboxyl | R | 0 | H | H | THP-4-yl |
(400MHz, DMSO-d6); δ 12.42(br s, 1H), 11.34(s, 1H), 6.80(d, 1H), 6.72(s, 1H), 1R), 6.80(d, 6.33(d, 1H), 5.79(d, 1H), 4.86(q, 1H), 3.88(m, 2H), 3.60-3.52(m, 2H), 3.42(t, 2H), 3.17(m, 1H), 2.74(m, 1H), 2.59(m, 1H), 1.94(m, 2H),1.39(m, 2H) | ||||||
Reference Example 79 | HO- | R | 2 | H | H | THP-4-yl |
(400MHz, DMSO-d6); δ 11.29(s, 1H), 6.79(m, 2H), 6.70(s, 1H), 6.33(d, 1H), 5.76(d, 1H), 4.66(q, 1H), 4.54(t, 1H), 3.88(m, 2H), 3.62-3.59(m, 3H), 3.53(t, 1H), 3.43(m, 2H), 3.12(m, 1H), 1.96(m, 3H), 1.75(m, 1H), 1.40(m, 2H) | ||||||
80 | MeO2C- | R | 1 | methoxy | H | c-Pen |
(400MHz, DMSO-d6); δ 11.24(s, 1H), 6.62(s, 1H), 6.22(s, 1H), 5.89(d, 1H), 5.84(s, 1H), 4.83(q, 1H), 3.77(m, 1H), 3.64(s, 3H), 3.59(s, 3H), 3.56(m, 1H), 3.15(m, 1H), 2.69(m, 1H), 2.58(m, 1H), 1.90(m, 2H), 1.67(m, 2H), 1.51(m, 4H) | ||||||
81 | carboxyl | R | 1 | methoxy | H | c-Pen |
(400MHz, DMSO-d6); δ 12.54(br s, 1H), 11.21(s, 1H), 6.63(s, 1H), 6.23(s, 1H), 5.89(d, 1H), 5.84(s, 1H), 4.84(q, 1H), 3.77(m, 1H), 3.64(s, 3H), 3.56(m, 1H), 3.15(m, 1H), 2.69(m, 1H), 2.58(m, 1H), 1.90(m, 2H), 1.67(m, 2H), 1.52(m, 4H) | ||||||
Reference Example 82 | carboxyl | R | 1 | methoxy | H | THP-4-yl |
(500MHz, DMSO-d6); δ 11.21(br s, 1H), 6.64(m, 1H), 6.26(m, 1H), 5.95(m, 1H), 5.84(m, 1H), 4.85(m, 1H), 3.85(m, 1H), 3.64(s, 3H), 3.63-3.49(m, 2H), 3.43(m, 2H), 3.17(m, 1H), 2.73(m, 1H), 2.62(m, 1H), 1.94(m, 2H), 1.72(m, 1H), 1.38(m, 2H) | ||||||
83 | carboxyl | R | 1 | ethoxy | H | c-Pen |
(400MHz, DMSO-d6); δ 11.24(br s, 1H), 6.65(d, J=2.0Hz, 1H), 6.26(d, J=2.0Hz, 1H), 5.92(d, J=6.0Hz, 1H), 5.88(d, J=2.0Hz, 1H), 4.89(m, 1H), 3.94(q, 2H), 3.81(m, 1H), 3.65(m, 1H), 3.20(m, 1H), 2.74(m, 1H), 2.62(m, 1H), 1.94(m, 2H), 1.72(m, 2H), 1.61(m, 4H), 1.31(t, 3H) | ||||||
84 | carboxyl | R | 1 | O(n-Pr) | H | c-Pen |
(500MHz,, CDCl3); δ 12.79(br s, 1H), 7.05(s, 1H), 6.26(s, 1H), 6.22(s, 1H), 5.14(br s, 1H), 3.88(m, 3H), 3.41(m, 2H), 3.07(m, 1H), 2.83(m, 1H), 2.03(m, 2H), 1.82(m, 3H), 1.69(m, 2H),1.60(m, 2H), 1.04(t, 3H) | ||||||
85 | carboxyl | R | 1 | phenoxy | H | c-Pen |
(400MHz, CDCl3); δ 11.92(br s, 1H), 7.28(m, 2H), 7.00(m, 4H), 6.56(s, 1H), 6.22(s, 1H), 5.34(br s, 1H), 3.81(br s, 1H), 3.70(m, 1H), 3.22(d, J=12.0Hz, 1H), 2.76∼2.62(m, 2H), 1.96(m, 2H), 1.73(m, 2H), 1.58(m, 4H) | ||||||
Reference Example 86 | carboxyl | R | 1 | phenoxy | H | THP-4-yl |
(400MHz, CDCl3); δ 11.98(br s, 1H), 7.28(m, 2H), 7.00(m, 4H), 6.58(s, 1H), 6.22(s, 1H), 5.34(br s, 1H), 3.98(br s, 2H), 3.70(m, 1H), 3.50(m, 3H), 3.21(m, 2H), 2.74(m, 1H), 2.66(m, 1H), 2.05(m, 2H), 1.58(m, 2H) | ||||||
87 | MeO2C- | R | 1 | pyridin-3-yl)oxy | H | c-Pen |
(400MHz, CDCl3); δ 10.89(br s, 1H), 8.41(d, 1H), 8.26(m, 1H), 7.27(m, 1H), 7.19(m, 1H), 6.85(s, 1H), 6.62(d, 1H), 6.22(m, 1H), 5.04(m, 1H), 4.13(br s, 1H), 3.78(m, 1H), 3.65(m, 1H), 3.59(s, 3H), 3.20(m, 1H), 2.83(m, 1H), 2.67(m, 1H), 1.98(m, 2H), 1.61(m, 4H), 1.46(m, 2H) | ||||||
88 | carboxyl | R | 1 | (pyridin-3-yl)oxy | H | c-Pen |
(400MHz, CDCl3); δ 11.86(br s, 1H), 8.40(d, 1H), 8.26(m, 1H), 7.25(m, 1H), 7.17(m, 1H), 6.96(s, 1H), 6.57(d, 1H), 6.18(d, 1H), 5.33(br s, 1H), 3.80(br s, 1H), 3.70(m, 1H), 3.21(m, 1H), 2.73(m, 1H), 2.65(m, 1H), 1.96(m, 2H), 1.72(m, 2H), 1.58(m, 4H) | ||||||
Reference Example 89 | MeO2C- | R | 1 | (pyridin-3-yl)oxy | H | THP-4-yl |
(400MHz, DMSO-d6); δ 11.48(br s, 1H), 8.30(d, 1H), 8.25(m, 1H), 7.34(m, 1H), 7.29(m, 1H), 6.76(d, 1H), 6.46(d, 1H), 6.18(d, 1H), 4.93(m, 1H), 3.87(m, 3H), 3.66(s, 3H), 3.59(m, 1H), 3.44(m, 2H), 3.23(m, 1H), 2.81(m, 2H), 1.95(m, 2H), 1.43(m, 2H) | ||||||
Reference Example 90 | carboxyl | R | 1 | (pyridin-3-yl)oxy | H | THP-4-yl |
(400MHz, MeOH-d4); δ 8.14(s, 1H), 8.07(s, 1H), 7.25(m, 2H), 6.76(s, 1H), 6.45(s, 1H), 6.12(d, 1H), 4.84(m, 1H), 3.85(m, 1H), 3.83(m, 1H), 3.53(m, 1H), 3.40(m, 2H), 3.21(m, 2H), 3.12(m, 1H), 2.73(m, 1H), 2.59(m, 1H), 1.93(m, 2H), 1.46(m, 2H) | ||||||
91 | MeO2C- | R | 1 | methyl | H | c-Pen |
(400MHz, DMSO-d6); δ 11.19(s, 1H), 6.62(s, 1H), 6.55(s, 1H), 6.07(s, 1H), 5.75(d, 1H), 4.88(q, 1H), 3.79(m, 1H), 3.63-3.57(m, 5H), 3.17(m, 1H), 2.82-2.73(m, 2H), 2.23(s, 3H), 1.94(m, 2H), 1.68(m, 2H), 1.55(m, 3H) | ||||||
92 | carboxyl | R | 1 | methyl | H | c-Pen |
(400MHz, DMSO-d6); δ 12.42(br s, 1H), 11.21(s, 1H), 6.61(s, 1H), 6.54(s, 1H), 6.02(s, 1H), 5.76(d, 1H), 4.87(q, 1H), 3.77(m, 1H), 3.62(t, 2H), 3.16(m, 1H), 2.81-2.72(m, 2H), 2.23(s, 3H), 1.94(m, 2H), 1.68(m, 2H), 1.55(m, 3H) | ||||||
Reference Example 93 | carboxyl | R | 1 | methyl | H | THP-4-yl |
(500MHz, CDCl3); δ 11.85(br s, 1H), 6.97(d, 1H), 6.76(s, 1H), 6.26(s, 1H), 5.32(m, 1H), 3.99(m, 2H), 3.71(m, 1H), 3.65(m, 1H), 3.54(m, 2H), 3.23(m, 1H), 2.76(m, 1H), 2.64(m, 1H), 2.31(s, 3H), 2.06(m, 2H), 1.58(m, 2H) | ||||||
94 | carboxyl | R | 1 | 4-(methanesulfon yl)phenoxy | H | c-Pen |
(500MHz, DMSO-d6); δ 11.71(br s, 1H), 7.81(d, 2H), 7.05(m, 2H), 6.65(s, 1H), 6.49(s, 1H), 6.35(m, 1H), 5.96(s, 1H), 4.86(m, 1H), 3.75(m, 1H), 3.52(m, 1H), 3.17(m, 1H), 3.12(s, 3H), 1.87(m, 2H), 1.67(m, 2H), 1.53(m, 4H) | ||||||
95 | MeO2C- | R | 1 | phenoxymethyl | H | c-Pen |
(500MHz, CDCl3); δ 9.49(br s, 1H), 7.27(m, 2H), 7.10(s, 1H), 7.01(m, 2H), 6.93(m, 1H), 6.89(s, 1H), 6.59(s, 1H), 5.07(s, 2H), 5.02(m, 1H), 3.93(m, 1H), 3.71(s, 3H), 3.65(m, 1H), 3.21(m, 1H), 2.88(m, 1H), 2.68(m, 1H), 2.04(m, 2H), 1.75(m, 2H), 1.58(m, 4H) | ||||||
96 | MeO2C- | R | 1 | phenylaminomethyl | H | c-Pen |
(500MHz, CDCl3); δ 9.47(br s, 1H), 7.21(dd, 2H), 7.07(s, 1H), 6.88(s, 1H), 6.75(m, 3H), 6.57(s, 1H), 5.08(m, 1H), 4.35(s, 2H), 3.94(m, 1H), 3.72(s, 3H), 3.68(m, 1H), 3.23(m, 1H), 2.92(m, 1H), 2.10∼1.30(m, 8H) | ||||||
97 | MeO2C- | R | 1 | methanesulfony lmethyl | H | c-Pen |
(500MHz, CDCl3); δ 10.22(br s, 1H), 7.00(s, 1H), 6.87(s, 1H), 6.50(s, 1H), 5.05(m, 1H), 4.27(s, 2H), 3.87(m, 1H), 3.61(s, 3H), 3.22(m, 1H), 2.83(m, 1H), 2.72(s, 3H), 2.66(m, 1H), 2.03(m, 2H), 1.64(m, 4H), 1.46(m, 2H) | ||||||
98 | carboxyl | R | 1 | methanesulfony lmethyl | H | c-Pen |
(400MHz, DMSO-d6); δ 11.68(br s, 1H), 6.85(s, 1H), 6.71(s, 1H), 6.33(s, 1H), 6.18(m, 1H), 4.88(m, 1H), 4.35(s, 2H), 3.84(m, 1H), 3.56(m, 1H), 3.20(m, 1H), 2.84(s, 3H), 2.55(m, 1H), 2.09(m, 1H), 1.97(m, 2H), 1.73(m, 2H), 1.58(m, 4H) | ||||||
99 | HO- | R | 2 | methanesulfony lmethyl | H | c-Pen |
(500MHz, CDCl3); δ 10.41(br s, 1H), 6.98(s, 1H), 6.90(s, 1H), 6.49(s, 1H), 4.68(m, 1H), 4.28(s, 2H), 3.96(m, 3H), 3.59(m, 1H), 3.13(m, 1H), 2.05(m, 4H), 1.72(m, 2H), 1.60(m, 4H) | ||||||
100 | EtNHC(O )- | R | 1 | H | H | c-Pen |
(400MHz, CDCl3); δ 9.66, 7.08∼6.99(m, 2H), 6.92(d, 1H), 6.55(d, J=7.2Hz, 1H), 5.88(m, 1H), 5.02(m, 1H), 4.13(m, 1H), 3.61(m, 1H), 3.32∼3.18(m, 3H), 2.67(1H, m), 2.52(m, 1H), 2.04(m, 1H), 1.72∼1.53(m, 6H), 1.08(m, 3H) | ||||||
101 | carboxyl | R | 2 | chloro | H | c-Pen |
(400MHz, DMSO-d6, Na salt); δ 11.69(br s, 1H), 6.82(d, J=4.0Hz, 1H), 6.68(s, 1H), 6.27(s, 1H), 6.18(s, 1H), 4.63(m, 1H), 3.83(m, 1H), 3.50(m, 1H), 3.13(m, 1H), 2.08∼1.96(m, 6H), 1.72(m, 2H), 1.58(m, 4H) | ||||||
102 | HO- | R | 3 | chloro | H | c-Pen |
(400MHz, CDCl3); δ 10.42(br s, 1H), 6.94(s, 1H), 6.82(s, 1H), 6.37(s, 1H), 4.58(m, 1H), 4.56(m, 1H), 3.75(m, 2H), 3.65(m, 1H), 1.95(m, 7H), 1.51(m, 4H), 1.31(m, 2H) | ||||||
Reference Example 103 | carboxyl | R | 2 | chloro | H | THP-4-yl |
(400MHz, DMSO-d6, Na salt); δ 11.53(br s, 1H), 6.86(s, 1H), 6.76(s, 1H), 6.34(s, 1H), 4.67(m, 1H), 3.91(m, 2H), 3.49(m, 4H), 3.21(m, 1H), 2.50(m, 2H), 2.01(m, 4H), 1.43(m, 2H) | ||||||
Reference Example 104 | HO- | R | 3 | chloro | H | THP-4-yl |
(400MHz, CDCl3); δ 11.00(br s, 1H), 6.93(s, 1H), 6.82(s, 1H), 6.31 (s, 1H), 4.89(br s, 1H), 4.56(m, 1H), 3.95 (m, 1H), 3.85(m, 1H), 3.77(m, 1H), 3.65(m, 1H), 3.51(m, 4H), 3.10(m, 1H), 1.97(m, 2H), 1.83(m, 3H), 1.74(m, 1H), 1.44(m, 1H), 1.40(m, 1H) | ||||||
105 | EtO2C- | R | 2 | methyl | H | c-Pen |
(400MHz, CDCl3); δ 10.75(br s, 1H), 6.82(d, 2H), 6.32(s, 1H), 4.71(m, 1H), 4.01(q 2H), 3.83(m, 1H), 3.53(m, 1H), 3.11(m, 1H), 2.44(m, 2H), 2.37(s, 3H), 2.01(m, 4H), 1.64(m, 4H), 1.40(m, 2H) | ||||||
106 | carboxyl | R | 2 | methyl | H | c-Pen |
(400MHz, CDCl3); δ 1134(br s, 1H), 6.56(s, 1H), 6.54(s, 1H), 6.06(s, 1H), 5.05(br d, 1H), 4.60(m, 1H), 3.81(m, 1H), 3.45(m, 1H), 3.06(m, 1H), 2.28(s, 3H), 2.09∼1.93(m, 5H), 1.78∼1.54(m, 7H) | ||||||
107 | carboxyl | R | 2 | phenoxy | H | c-Pen |
(400MHz, DMSO-d6); δ 11.59(br s, 1H), 7.29(m, 2H), 7.01(m, 1H), 6.92(m, 2H), 6.67(s, 1H), 6.40(d, 1H), 6.21(d, 1H), 5.99(d, 1H), 4.63(m, 1H), 3.75(m, 1H), 3.50(m, 1H), 3.11(m, 1H), 2.08(m, 2H), 2.03(m, 1H), 1.90(m, 2H), 1.81(m, 1H), 1.71(m, 2H), 1.56(m, 4H) | ||||||
108 | EtO2C- | R | 2 | fluoro | H | c-Pen |
(400MHz, CDCl3); δ 10.48(br s, 1H), 6.91(s, 1H), 6.69(m, 1H), 6.30(m, 1H), 4.77(m, 1H), 4.19∼4.02(m, 3H), 3.84(m, 1H), 3.60(m, 1H), 3.18(m, 1H), 2.51(m, 2H), 2.07(m, 4H), 1.74∼1.46(m, 6H), 1.21(m, 3H) | ||||||
109 | carboxyl | R | 2 | fluoro | H | c-Pen |
(400MHz, DMSO-d6); δ 11.63(br s, 1H), 6.49(m, 1H), 6.33(m, 1H), 6.09(m, 1H), 6.66(m, 1H), 4.61(m, 1H), 3.85(m, 1H), 3.52(m, 1H), 3.11(m, 1H), 2.09∼1.74(m, 12H), | ||||||
110 | EtO2C- | R | 2 | bromo | H | c-Pen |
(400MHz, CDCl3); δ 10.02(br s, 1H), 7.16(s, 1H), 6.81(s, 1H), 6.57(s, 1H), 4.74(m, 1H), 4.11(m, 2H), 4.02(m, 2H), 3.59(q, 1H), 3.16(q, 1H), 2.52(m, 2H), 2.06(m, 4H), 1.72(m, 3H), 1.49(m, 2H), 1.19(t, 3H) | ||||||
111 | carboxyl | R | 2 | bromo | H | c-Pen |
(400MHz, DMSO-d6); δ 11.77(br s, 1H), 6.96(s, 1H), 6.68(s, 1H), 6.31(m, 1H), 6.29(s, 1H), 4.64(m, 1H), 3.82(m, 1H), 3.53(m, 1H), 3.13(m, 1H), 2.05(m, 2H), 1.97(m, 2H), 1.77(m, 3H), 1.58(m, 4H) | ||||||
112 | carboxyl | R | 2 | H | H | c-Pen |
(400MHz, DMSO-d6); δ 11.46(br s, 1H), 6.85(m, 2H), 6.70(s, 1H), 6.27(d, J=4.0Hz, 1H), 5.94(d, J=8.0Hz, 1H), 4.65(m, 1H), 3.86(m, 1H), 3.52(m, 1H), 3.11(m, 1H), 2.05(m, 2H), 1.97(m, 3H), 1.78(m, 3H), 1.56(m, 4H) | ||||||
113 | carboxyl | R | 2 | methoxy | H | c-Pen |
(400MHz, DMSO-d6); δ 11.28(br s, 1H), 6.61(s, 1H), 6.27(s, 1H), 5.97(m, 1H), 5.88(s, 1H), 4.59(m, 1H), 3.75(m, 1H), 3.68(s, 3H), 3.48(m, 2H), 3.08(m, 1H), 2.00(m, 5H), 1.75(m, 3H), 1.57(m, 4H) | ||||||
114 | EtO2C- | R | 2 | ethoxy | H | c-Pen |
(500MHz, CDCl3); δ 9.79(br s, 1H), 6.80(s, 1H), 6.44(s, 1H), 6.19(s, 1H), 4.69(m, 1H), 4.11(q, 2H), 4.03(q, 2H), 3.83(m, 1H), 3.54(m, 1H), 3.11(m, 1H), 2.49(m, 2H), 2.02(m, 4H), 1.69(m, 2H), 1.60(m, 2H), 1.48(m, 2H), 1.25(t, 3H), 1.19(t, 3H) | ||||||
115 | carboxyl | R | 2 | ethoxy | H | c-Pen |
(400MHz, DMSO-d6); δ 11.37(br s, 1H), 6.78(s, 1H), 6.30(s, 1H), 5.94(s, 1H), 4.64(m, 1H), 3.93(q, 2H), 3.82(m, 1H), 3.60(m, 1H), 3.21(m, 1H), 2.44(m, 2H), 1.97(m, 4H), 1.71(m, 2H), 1.57(m, 4H), 1.32(t, 3H) | ||||||
116 | EtO2C- | R | 2 | OCF3 | H | c-Pen |
(500MHz, CDCl3); δ 10.97(br s, 1H), 6.93(s, 1H), 6.86(s, 1H), 6.30(s, 1H), 4.76(m, 1H), 4.05-3.89(m, 3H), 3.78(m, 1H), 3.57(m, 1H), 3.16(m, 2H), 2.42(m, 2H), 2.00(m, 4H), 1.63(m, 2H), 1.45(m, 1H), 1.34(m, 1H) | ||||||
117 | carboxyl | R | 2 | OCF3 | H | c-Pen |
(40MHz, DMSO-d6) 11.61(br s, 1H), 6.85(d, 1H), 6.77(s, 1H), 6.16(s, 1H), 4.66(m, 1H), 3.85(m, 1H), 3.60(m, 2H), 3.20(m, 1H), 2.42(m, 2H), 1.99(m, 4H), 1.71(m, 2H), 1.58(m, 4H) |
Examples 118 to 123:
Examp le | R1 | * | n | R2 | R4 |
H1 NMR data | |||||
Reference Example 118 | hydroxy | S | 2 | methyl | THP-4-yl |
(400MHz, CDCl3); δ 10.11(br s, 1H), 6.91(s, 1H), 6.86(s, 1H), 6.34(s, 1H), 4.60(t, 1H), 4.48(m, 1H), 4.10∼3.93(m, 5H), 3.63∼3.52(m 3H), 2.39(s, 3H), 2.07(d, 2H), 1.94(m, 2H), 1.58(m, 2H) | |||||
119 | carboxyl | S | 1 | methyl | c-Pen |
(400MHz, CDCl3/MeOH-d4); δ, 6.97(s, 1H), 6.79(s, 1H), 6.33(s, 1H), 4.86(m, 1H), 4.62(dd, 1H), 4.35(dd,1H), 3.95(m, 1H), 2.94(dd, 1H), 2,67(dd,1H), 2.39(s, 3H), 2.07(m, 2H), 1,78(m, 2H), 1.65(m, 4H) | |||||
Reference Example 120 | carboxyl | S | 1 | methyl | THP-4-yl |
(400MHz, CDCl3/MeOH-d4); δ 6.94(s, 1H), 6.81(s, 1H), 6.32(s, 1H), 4.87(m, 1H), 4.59(dd, 1H), 4.34(dd, 1H), 4.02(d, 1H), 3.68∼3.58(m, 3H), 2.92(dd, 1H), 2.68(dd, 1H), 2.38(s, 3H), 2.13(d, 2H), 1.57(m, 2H) | |||||
121 | carboxyl | S | 1 | Cl | c-Pen |
(400MHz, CDCl3/MeQH-d4); δ 6.89(s, 1H), 6.85(s, 1H), 6.30(s, 1H), 4.79(m, 1H), 4.55(dd, 1H), 4.30(dd, 1H), 3.82(m, 1H), 2.86(dd, 1H), 2.264(dd, 1H), 2.01(m, 2H), 1.71(m, 2H), 1.57(m, 4H) | |||||
Reference Example 122 | carboxyl | S | 1 | Cl | (THP-4-yl)methyl |
(400MHz, MeOH-d4); δ 6.96(s, 1H), 6.84(s, 1H), 6.27(s, 1H), 4.78(m, 1H), 4.60(dd, 1H), 4.31(dd, 1H), 3.94(dd, 2H), 3.40(m, 2H), 3.08(d, 2H), 2.98(dd, 2H), 2.64(d, 2H), 1.94(m,1H), 1.75(m, 2H), 1.37(m, 2H) | |||||
(400MHz, MeOH-d4); δ 7.36-7.18 (6H, m), 6.95 (1H, s), 6.75 (1H, s), 6.27 (1H, d, J=1.2 Hz), 3.84 (1H, brs), 3.77 (1H, brs), 3.66-3.56 (1H, m), 3.34 (1H, brs), 2.77 (2H, brs), 1.93 (2H, brs), 1.54-1.48 (6H, m) | |||||
Reference Example 123 | H | - | 0 | H | THP-4-yl |
NMR (500MHz, CDCl3); δ 11.38(br s, 1H), 7.10(d, 8Hz, 1H), 7.00∼6.98(m, 2H), 6.52(d, J=8.0Hz, 1H), 4.50(m, 2H), 4.12(m, 2H), 4.00(m, 2H), 3.58(m, 1H), 3.50(m, 2H), 2.04(m, 2H), 1.47(m, 2H) |
Example 124: [2-((4S,5R)-5-aminomethyl-4-benzyl-dihydro-oxazol-2-yl)-5-chloro-1H-indol-7-yl]-cyclopentyl-amine
Step A: 2-[(4S,5R)-benzyl-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-oxazol-5-ylmethyl]isoindol-1,3-dione
Step B: [2-((45,5R)-5-aminomethyl-4-benzyl-dihydro-oxazol-2-yl)-5-chloro-1H-indol-7-yl]-cyclopentyl-amine
Example 125: {2-[(R)-5-((S)-1-amino-2-phenyl-ethyl-4,5-dihydro-oxazol-2-yl]-5-chloro-1H-indol-7-yl}-cyclopentylamine
Examples 126 to 134:
Example | A | R1 | n | R2 | R4 |
H1 NMR data | |||||
Reference Example 126 | isoxadiazol-3-yl | 5-carboxyl | 1 | H | THP-4-yl |
(500HMz, CDCl3, MeOH-d4); δ 7.20(s, 1H), 6.96(d, J=8.0Hz, 1H), 6.92(t, J=8.0Hz, 1H), 6.42(d, J=7.4Hz, 1H), 3.96(m, 2H), 3.83(s, 2H), 3.57(m, 1H), 3.49(m, 2H), 2.02(m, 2H), 1.54(m, 2H) | |||||
Reference Example 127 | isoxadiazol-3-yl | 5-hydroxy | 2 | H | THP-4-yl |
(400MHz, CDCl3); δ 10.40(br s, 1H), 7.27(s, 1H), 7.08(d, J=8.0Hz, 1H), 7.04(t, J=8.0Hz, 1H), 6.55(d, J=7.4Hz, 1H), 4.11(m, 4H), 3.70(m, 1H), 3.61(t, 2H), 3.06(m, 2H), 2.14(m, 2H), 1.66(m, 2H) | |||||
128 | oxadiazol-2-yl | H | 0 | methyl | c-Pen |
(400MHz, CDCl3); δ 9.97(br s, 1H), 8.43(s, 1H), 7.10(s, 1H), 6.81(s, 1H), 6.40(s, 1H), 4.15(br s, 1H), 3.94(m, 1H), 2.42(s, 3H), 2.04(m, 2H), 1.73(m, 2H), 1.63(m, 2H), 1.54(m, 2H) | |||||
129 | thiazol-2-yl | 4-hydroxy | 1 | methyl | c-Pen |
(400MHz, CDCl3); δ 10.42(br s, 1H), 7.14(s, 1H), 6.88(d, J=4Hz, 1H), 6.86(s, 1H), 6.36(s, 1H), 4.70(s, 2H), 3.86(m, 1H), 3.69(br s, 1H), 2.39(s, 3H), 1.95(m, 2H), 1.37(m, 4H), 1.26(m, 2H) | |||||
130 | thiazol-2-yl | 5-hydroxy | 1 | methyl | c-Pen |
(400MHz, DMSO-d6); δ 11.39(s, 1H), 7.70(s, 1H), 6.78(s, 1H), 6.60(s, 1H), 1H), 5.72(d, J=8Hz, 1H), 5.62(m, 1H), 4.72(d, J=4Hz, 2H), 3.88(m, 1H), 2.30(s, 3H), 1.99(m, 2H), 1.74(m, 2H), 1.57(m, 4H) | |||||
131 | thiazol-2-yl | 4-EtO2C- | 0 | methyl | c-Pen |
(400MHz, CDCl3); δ 9.36(br s, 1H), 8.07(s, 1H), 6.91(d, J=4Hz, 1H), 6.84(s, 1H), 6.37(s, 1H), 4.37(q, 2H), 3.95(m, 1H), 3.64(br s, 1H), 2.40(s, 3H), 2.04(m, 2H), 1.76(m, 2H), 1.65(m, 2H), 1.55(m, 2H), 1.33(t, 3H) | |||||
132 | thiazol-2-yl | 4-carboxyl | 0 | methyl | c-Pen |
(400MHz, DMSO-d6, Na salt); δ 7.89(s, 1H), 6.81(s, 1H), 6.65(br s, 1H), 6.59(s, 1H), 6.13(s, 1H), 3.87(m, 1H), 2.31(s, 3H), 2.01(m, 2H), 1.75(m, 4H), 1.55(m, 2H) | |||||
133 | thiazol-2-yl | 4-hydroxy | 1 | c-Pen | |
(400MHz, CDCl3); δ 10.60(br s, 1H), 7.14(s, 1H), 6.99(m, 3H), 6.53(d, J=8Hz, 1H), 4.71(s, 2H), 3.87(m, 1H), 3.74(m, 1H), 1.96(m, 2H), 1.59(m,4H), 1.37(m, 2H) | |||||
134 | thiazol-2-yl | 4-MeO2C- | 0 | H | c-Pen |
(400MHz, CDCl3); δ 9.31(br s, 1H), 8.08(s, 1H), 7.05(m, 3H), 6.56(d, j+8Hz, 1H), 3.96(s, 3H), 3.73(m, 1H), 2.07(m, 2H), 1.80(m, 2H), 1.67(m, 4H) |
Reference Example Example 135: {(R)-2-[5-methyl-7-(4-oxo-cyclohexylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl} acetic acid
Step A: {(R)-2-[7-(1,4-dioxa-spiro[4.5]dec-8-ylamino)-5-methyl-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-acetic acid ethyl ester
Step B: {(R)-2-[5-methyl-7-(4-oxo-cyclohexylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-y} acetic acid
Example 136: 2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-morpholin-4-yl-ethanone
Examples 137 to 155:
Example | R1' | * | n | R2 | R4 |
H1 NMR data | |||||
137 | 1-(morpholin-4-yl)ethylamino | R | 1 | chloro | c-Pen |
(500MHz, DMSO-d6); δ 11.53(br s, 1H), 7.91(m, 1H), 6.80(s, 1H), 6.70(s, 1H), 6.16(s, 1H), 6.12(m, 1H), 4.93(m, 1H), 3.80(m, 1H), 3.53(m, 5H), 3.20(m, 3H), 2.60(m, 1H), 2.32(m, 7H), 1.93(m, 2H), 1.68(m, 2H), 1.53(m, 4H) | |||||
138 | 1-(morpholin-4-yl)propylamino | R | 1 | chloro | c-Pen |
(500MHz, DMSO-d6); δ 11.52(br s, 1H), 7.94(m, 1H), 6.79(s, 1H), 6.70(s, 1H), 6.16(s, 1H), 6.12(m, 1H), 4.93(m, 1H), 3.80(m, 1H), 3.51(m, 5H), 3.10(m, 3H), 2.59(m, 1H), 2.37(m, 1H), 2.25(m, 6H), 1.93(m, 2H), 1.68(m, 2H), 1.53(m, 6H) | |||||
139 | methylamino | R | 1 | chloro | c-Pen |
(500MHz, DMSO-d6); δ 11.52(br s, 1H), 7.90(m, 1H), 6.80(s, 1H), 6.69(s, 1H), 6.16(s, 1H), 6.13(m, 1H), 4.93(m, 1H), 3.80(m, 1H), 3.55(m, 1H), 3.15(m, 1H), 2.58(m, 4H), 2.39(m, 1H), 1.93(m, 2H), 1.68(m, 2H), 1.56(m, 4H) | |||||
140 | dimethylamino | R | 1 | chloro | c-Pen |
(500MHz, DMSO-d6); δ 11.53(br s, 1H), 6.79(s, 1H), 6.69(s, 1H), 6.16(s, 1H), 6.12(m, 1H), 4.93(m, 1H), 3.81(m, 1H), 3.63(m, 1H), 3.15(m, 1H), 2.95(s, 3H), 2.87(m, 1H), 2.83(s, 3H), 2.65(m, 1H), 1.93(m, 2H), 1.69(m, 2H), 1.53(m, 4H) | |||||
141 | 4-(methyl)piperazin-1-yl | R | 1 | chloro | c-Pen |
(500MHz, DMSO-d6); δ 11.52(br s, 1H), 6.80(s, 1H), 6.69(s, 1H), 6.16(s, 1H), 6.12(m, 1H), 4.94(m, 1H), 3.80(m, 1H), 3.62(m, 1H), 3.42(m, 4H), 3.35(m, 1H), 3.15(m, 1H), 2.85(m, 1H), 2.66(m, 1H), 2.24(m, 4H), 2.13(s, 3H), 1.93(m, 2H), 1.68(m, 2H), 1.55(m, 4H) | |||||
142 | 3-dimethylaminopyrrolidin-1-yl | R | 1 | chloro | c-Pen |
(500MHz, DMSO-d6); δ 11.53(br s, 1H), 6.80(s, 1H), 6.69(s, 1H), 6.16(s, 1H), 6.12(m, 1H), 4.94(m, 1H), 3.81(m, 1H), 3.62(m, 3H), 3.30(m, 1H), 3.17(m, 2H), 2.78(m, 1H), 2.53(m, 2H), 2.11(s, 3H), 2.07(s, 3H), 1.93(m, 2H), 1.69(m, 3H), 1.59(m,5H) | |||||
143 | piperidin-1-yl | R | 1 | chloro | c-Pen |
(500MHz, DMSO-d6); δ 11.52(br s, 1H), 6.80(s, 1H), 6.69(s, 1H), 6.16(s, 1H), 6.12(m, 1H), 4.94(m, 1H), 3.81(m, 1H), 3.63(m, 1H), 3.45(m, 1H), 3.38(m, 3H), 3.14(m, 1H), 2.85(m, 1H),1.93(m, 2H), 1.68(m, 2H),1.48(m, 10H) | |||||
Reference Example 144 | methylamino | R | 1 | chloro | THP-4-yl |
(500MHz, DMSO-d6); δ 11.54(br s, 1H), 7.91(m, 1H), 6.81(s, 1H), 6.70(s, 1H), 6.28(s, 1H), 6.08(m, 1H), 4.93(m, 1H), 3.85(m, 2H), 3.56(m, 2H), 3.44(m, 2H), 3.15(m, 1H), 2.06(m, 4H), 2.37(m, 1H), 1.93(m, 2H), 1.39(m, 2H) | |||||
Reference Example 145 | morpholin-4-yl | R | 1 | chloro | THP-4-yl |
(500MHz, DMSO-d6); δ 11.53(br s, 1H), 6.81(s, 1H), 6.70(s, 1H), 6.28(s, 1H), 6.08(m, 1H), 4.96(m, 1H), 3.86(m, 2H), 3.47(m, 12H), 3.15(m, 1H), 2.85(m, 1H), 2.69(m, 1H), 1.94(m, 2H), 1.39(m, 2H) | |||||
146 | 4-(methyl)piperazin-1-yl | R | 1 | fluoro | c-Pen |
(400MHz, DMSO-d6); δ 11.44(br s, 1H), 6.73(s, 1H), 6.52(dd, 1H), 6.19(d, J=1.2Hz, 1H), 6.07(dd, 1H), 4.99(m, 1H), 3.84(m, 2H), 3.65(m, 1H), 3.49(m, 4H), 3.20(m, 1H), 2.88(m, 1H), 2.71(m, 1H), 2.28(m, 4H), 2.17(s, 3H), 1.98(m, 2H), 1.72(m, 2H), 1.58(m, 4H) | |||||
147 | (morpholin-4-yl)ethylamino | R | 1 | fluoro | c-Pen |
(400MHz, DMSO-d6); δ 11.46(br s, 1H), 7.95(m, 1H), 6.75(s, 1H), 6.73(dd, 1H), 6.18(d, J=4.0Hz, 1H), 6.07(dd, 1H), 5.00(m, 1H), 3.84(m, 1H), 3.58(m, 1H), 3.53(m, 4H), 3.20(m, 3H), 2.73(m, 1H), 2.45(m, 3H), 2.34(m, 4H), 1.98(m, 2H), 1.72(m, 2H), 1.59(m, 4H) | |||||
148 | methylamino | R | 1 | methoxy | c-Pen |
(500MHz, DMSO-d6); δ 11.22(br s, 1H), 7.90(m, 1H), 6.61(s, 1H), 6.23(s, 1H), 5.87(m, 1H), 5.85(s, 1H), 4.90(m, 1H), 3.76(m, 1H), 3.64(s, 3H), 3.52(m, 1H), 3.12(m, 1H), 2.58(m, 4H), 2.35(m, 1H), 1.91(m, 2H), 1.67(m, 2H), 1.53(m, 4H) | |||||
149 | morpholin-4-yl | R | 1 | methoxy | c-Pen |
(500MHz, DMSO-d6); δ 11.21(br s, 1H), 6.62(s, 1H), 6.24(s, 1H), 5.87(m, 1H), 5.85(s, 1H), 4.92(m, 1H), 3.77(m, 1H), 3.65(s, 3H), 3.60(m, 1H), 3.58-3.33(m, 8H), 3.13(m, 1H), 2.84(m, 1H), 2.66(m, 1H), 1.91(m, 2H), 1.67(m, 2H), 1.53(m, 4H) | |||||
150 | methylamino | R | 1 | H | c-Pen |
(500MHz, DMSO-d6); δ 11.33(br s, 1H), 7.90(m, 1H), 6.78(m, 1H), 6.71(s, 1H), 6.24(s, 1H), 5.80(m, 1H), 4.93(m, 1H), 3.81(m, 1H), 3.54(m, 1H), 3.14(m, 1H), 2.62(m, 1H), 2.58(m, 3H), 2.38(m, 1H), 1.93(m, 2H), 1.69(m, 2H), 1.54(m, 4H) | |||||
151 | morpholin-4-yl | R | 1 | H | c-Pen |
(500MHz, DMSO-d6); δ 11.32(br s, 1H), 6.78(m, 1H), 6.71(s, 1H), 6.24(s, 1H), 5.81(m, 1H), 4.95(m, 1H), 3.81(m, 1H), 3.61(m, 1H), 3.59-3.39(m, 8H), 3.15(m, 1H), | |||||
2.87(m, 1H), 2.68(m, 1H), 1.93(m, 2H), 1.68(m, 2H), 1.54(m, 4H) | |||||
Reference Example 152 | methylamino | R | 1 | H | THP-4-yl |
(500MHz, DMSO-d6); δ 11.34(br s, 1H), 7.90(m, 1H), 6.79(m, 1H), 6.72(s, 1H), 6.33(m, 1H), 5.76(m, 1H), 4.93(m, 1H), 3.86(m, 1H), 3.54(m, 2H), 3.43(m, 2H), 3.14(m, 1H), 2.61(m, 1H), 2.59(m, 3H), 2.38(m, 1H), 1.95(m, 2H), 1.40(m, 2H) | |||||
Reference Example 153 | morpholin-4-yl | R | 1 | H | THP-4-yl |
(500MHz, DMSO-d6); δ 11.34(br s, 1H), 6.79(m, 1H), 6.72(s, 1H), 6-33(m, 1H), 5.77(m, 1H), 4.95(m, 1H), 3.87(m, 1H), 3.61(m, 1H), 3.57-3.38(m, 11H), 3.15(m, 1H), 2.87(m, 1H), 2.68(m, 1H), 1.95(m, 2H), 1.40(m, 2H) | |||||
154 | (morpholin-4-yl)ethylamino | R | 2 | chloro | c-Pen |
(400MHz, CDCl3); δ zur s, 1H), 7.06(br s, 1H), 6.93(s, 1H), 6.82(s, 1H), 6.39(s, 1H), 4.61(m, 1H), 3.88(m, 2H), 3.77(s, 4H), 3.45(m, 2H), 3.07(m, 1H), 2.70(m, 6H), 2.44(m, 2H), 2.10(m, 3H), 1.95(m, 1H), 1.71(m, 2H), 1.64(m, 2H), 1.54(m, 2H) | |||||
155 | 4-(methyl)piperazin-1-yl | R | 2 | chloro | c-pen |
(400MHz, CDCl3); δ 10.33(br s, 1H), 6.97(s, 1H), 6.81(s, 1H), 6.42(s, 1H), 4.64(m, 1H), 3.85(m, 1H), 3.65(m, 2H), 3.56(m, 1H), 3.45(m, 2H), 3.13(m, 1H), 2.43(m, 6H), 2.04(m, 2H), 1.72(m, 8H), 1.54(m, 2H) |
Example 156: Cyclopentyl-{5-methanesulfonylmethyl-2-[(R)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine
Step A: Cyclopentyl-{2-[(R)-4-(2-iodo-ethyl)-4,5-dihydro-thiazol-2-yl]-5-methanesulfonylmethyl-1H-indol-7-yl}-amine
Step B: Cyclopentyl-{5-methanesulfonylmethyl-2-[(R)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine
Example 157: 1-(4-{2-[(R)-2-(7-cyclopentylamino-5-methanesulfonylmethyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanone
Example 158: Cyclopentyl-[2-((R)-4-pyrrolidin-1-ylmethyl-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl]-amine
Example 159: {5-Chloro-2-[(R)-4-(2-dimethylamino-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine
Example 160: {5-Chloro-2-[(R)-4-(2 piperazin-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine
Step A: {5-Chloro-2-[(R)-4-(2-1-BOC-piperazin-4-yl-ethyl)-4,5-dihydrothiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine
Step B: {5-Chloro-2-[(R)-4-(2-piperazin-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine
Example 161: (5-Chloro-2-{(R)-4-[2-(4-ethanesulfonyl-piperazin-1-yl)-ethyl]-45-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine
Example 162: 1-(4-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanone
Example 163: {5-Chloro-2-[(R)-4-(2-pyrazol-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine
Example 164: (S)-1-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-pyrrolidine-2-carboxlic acid
Step A: 2-{2-[(R)-2-(5-chloro-7-cvclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-pyrrolidine-2-carboxylic acid methyl ester
Step B: (S)-1-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-pyrrolidine-2-carboxylic acid
Example 165: {5-Chloro-2-[(R)-4-(2-methanesulfonyl-ethy)-4,5-dihydrothiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine
Example 166: 3-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-5-methyl-3H-imidazole-4-carboxylic acid ethyl ester
Example 167: 3-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-5-methyl-3H-imidazole-4-carboxylic acid
Reference Example 168: 1-(2-{(R)-2-[5-chloro-7-(tetrahyro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-piperidine-3-carboxylic acid
Step A: 1-(2-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-piperidine-3-carboxylic acid ethyl ester
Step B: 1-(2-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-piperidine-3-carboxylic acid
Reference Example 169: 1(S)-1-(2-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-pyrrolidin-3-yl]-carbamic acid t-butyl ester
Reference Example 170: (2-{(R)-4-[2-((S)-3-amino-pyrrolidin-1-yl)-ethyl]-4,5-dihydrothiazol-2-yl}-5-chloro-1H-indol-7-yl)-(tetrahydro-pyran-4-yl)-amine
Reference Example 171: N-[(S)-1-(2-{(R)-2-[5-chloro-7-(tetrahydro-pyran-4-ylamino)-1H-indol-2-yl]-4,5-dihydro-thiazol-4-yl}-ethyl)-pyrrolidin-3-yl]-acetamide
Example 172: Cyclonentyl-{2-[(R)-4-(2-methoxy-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine
Examples 173 to 224:
Example | R1 | * | n | R2 | R4 |
H1 NMR data | |||||
173 | amino | R | 1 | H | c-Pen |
(400MHz, DMSO-d6); δ 6.92(s, 1H), 6.86(m, 2H), 6.28(d, J=6Hz, 1H), 5.84(m, 1H), 4.24(m, 1H), 3.86(m, 2H), 3.56(m, 1H), 2.75(m, 2H), 1.97(m, 2H), 1.72(m, 2H), 1.56(m, 4H) | |||||
174 | (3R)-3-(amino)pyrrolidin-1-yl | R | 2 | chloro | c-Pen |
(400MHz, DMSO-d6); δ 11.24(s, 1H), 6.62(s, 1H), 6.22(s, 1H), 5.89(d, 1H), 5.84(s, 1H), 4.83(q, 1H), 3.77(m, 1H), 3.64(s, 3H), 3.59(s, 3H), 3.56(m, 1H), 3.15(run, 1H), 2.69(m,1H), 2.58(m, 1H), 1.90(m, 2H), 1.67(m, 2H), 1.51(m, 4H) | |||||
175 | 2-oxopiperazin-4-yl | R | 2 | methoxy | c-Pen |
(400MHz, CDCl3); δ 10.75(brs, 1H), 7.11(brs, 1H), 6.82(s, 1H), 6.39(d, J=4HZ, 1H), 6.13(d, J=4Hz, 1H), 4.71(m, 1H), 3.84(m, 1H), 3.81(s, 3H), 3.50(m, 1H), 3.28(m, 2H), 3.16(m, 2H), 3.08(m, 1H), 2.57(m, 4H), 2.01(m, 2H), 1.95(m, 1H), 1.84(m, 1H), 1.71(m, 2H), 1.57(m, 4H) | |||||
176 | (3S)-3-(amino)pyrrolidin-1-yl | S | chloro | c-Pen | |
(400MHz, MeOD); δ 7.51(s, 1H), 7.28(s, 1H), 7.06(s, 1H), 4.27(m, 1H), 4.15(m, 1H), 3.95-3.8(m, 5H), 3.67(m, 3H), 3.44(dd, 1H), 2.70(m, 1H), 2.40-2.25(m, 3H), 2.10(m, 2H), 1.91 (m, 4H), 1.71 (m, 2H) | |||||
177 | (3S)-3-(dimethylaminophenyl)ethyl aminopyrrolidin-1-yl | S | 2 | chloro | c-Pen |
(500Hz, CDCl3); δ 7.16(t, 1H), 6.89(s, 1H), 6.74(s, 1H), 6.61(m, 3H), 6.34(s, 1H), 4.64(m, 1H), 3.86(m, 1H), 3.66(m, 2H), 3.51(m, 2H), 3.45-3.25(br s, 2H), 3.25-3.05(br s, 2H), 3.03(t, 1H), 3.05-2.95(brs, 1H), 2.92(s, 6H), 2.38(br s, 1H), 2.05-1.85(m, 5H), 1.80-1.65(m, 4H), 1.58(m, 1H) | |||||
178 | 1-(acetyl)piperazin-4-yl | S | chloro | c-Pen | |
(500Hz, CDCl3); δ 10.17(br s, 1H), 7.00(s, 1H), 6.83(s, 1H), 6.43(s, 1H), 4.75(m, 1H), 3.83(m, 2H), 3.58(m, 1H), 3.56(dd, 1H), 3.48(m, 1H), 3.32(m, 1H), 3.25(m, 1H), 3.15(dd, 1H), 2.46(m, 2H), 2.36(m, 1H), 2.26(m, 2H), 2.20(m, 1H), 2.05(s, 3H), 2.04(m, 2H), 1.96(m, 1H), 1.80(m, 1B), 1.66(m, 3H), 1.48(m, 2H) | |||||
Reference Example 179 | 1-(acetyl)piperazin-4-yl | S | 2 | chloro | H |
(500Hz, DMSO); δ 11.70(br s, 1H), 10.41(s, 1H), 7.91(s, 1H), 7.78(d, 1H), 7.58(s, 1H), 7.46(s, 2H), 7.36(m, 3H), 7.09(t, 1H), 7.05(s, 1H), 6.97(d, 2H), 3.86(s, 2H), 2.90(brs, 2H) | |||||
180 | pyrrolidin-1-yl | R | 2 | methoxy | c-Pen |
(500MHz, CDCl3); δ 10.11(br s, 1H), 6.82(s, 1H), 6.44(s, 1H), 6.16(s, 1H), 4.72(m, 1H), 3.81(s, 3H), 3.74(m, 1H), 3.54(dd, 1H), 3.15(dd, 1H), 2.62(m, 1H), 2.46(m, 1H), 2.42(m, 4H), 2.01(m, 4H), 1.84(m, 1H), 1.73-1.64(m, 3H), 1.58(m, 2H), 1.50(m, 1H), 1.42(m, 1H) | |||||
Reference Example 181 | pyrrolidin-1-yl | R | 2 | H | THP-4-yl |
(500MHz, CDCl3); δ (2H, m), 7.51-7.47 (2H, m), 4.79-4.66 (4H, m), 4.39 (4H, brs), 3.73-3.55 (6H, m), 3.42-3.33 (6H, m), 3.04-2.98 (2H, m) | |||||
Reference Example 182 | 2-oxopiperazin-4-yl | S | 2 | methyl | THP-4-yl |
(500MHz, CDCl3); δ 11.05 (s, 1H), 7.72 (s, 1H), 6.82 (s, 1H), 6.78 (s, 1H), 6.27 (s, 1H), 4.71-4.67 (m, 1H), 4.03-4.01 (m, 2H), 3.62-3.47 (m, 4H), 3.30-3.20 (m, 2H, 3.15 (d, 2H), 3.11-3.08 (m, 1H), 2.59-2.53 (m, 4H), 2.42-2.36 (m, 3H), 2.09-2.04 (m, 2H), 1.95-1.92 (m, 1H), 1.84-1.81 (m, 1H, 1.59-1.51 (m, 2H) | |||||
183 | 2-oxopiperazin-4-yl | R | 2 | methane sulfonyl methyl | c-Pen |
(400MHz, CDCl3); δ 10.61 (brs, 1H), 6.97 (s, 1H), 6.85 (s, 1H), 6.72 (s, 1H), 6.48 (s, 1H), 4.75-4.69 (m, 2H), 4.28 (s, 2H), 3.93 (m, 1H), 3.58 (m, 1H), 3.42-3.23 (m, 3H), 3.19-3.10 (m, 2H), 2.75-2.52 (m, 6H), 2.06 (m, 2H), 1.93 (m, 2H), 1.74 (m, 2H), 1.68-1.53 (m, 6H) | |||||
Reference Example 184 | morpholin-4-yl | S | 2 | methyl | THP-4-yl |
(400MHz, CDCl3); δ 10.91(s, 1H), 6.85(s, 1H), 6.83(s, 1H), 6.28(s, 1H), 4.81(m, 1H), 3.96(m, 2H), 3.60∼3.41(m, 7H), 3.17(, 1H), 2.40(m, 2H), 2.36(s, 3H), 2.29(m, 2H), 2.18(m, 2H), 2.04∼1.79(m, 4H), 1.39(m, 2H) | |||||
185 | 1-(acetyl)piperazin-4-yl | R | 2 | chloro | c-Pen |
(500MHz, DMSO-d6); δ 11.47(br s, 1H), 6.79(s, 1H), 6.68(s, 1H), 6.16(s, 1H), 6.11(m, 1H), 4.62(m, 1H), 3.80(m, 1H), 3.55(m, 1M), 3.39(m, 4H), 3.15(m, 1H), 2.46(m, 1H), 2.32(m, 4H), 1.95(m, 4H), 1.80(m, 1H), 1.68(m, 2H), 1.53(m, 4H) | |||||
186 | 4-methyl-piperazin-1-yl | R | 2 | chloro | c-Pen |
(500MHz, DMSO-d6); δ 11.47(br s, 1H), 6.79(s, 1H), 6.67(s, 1H), 6.16(s, 1H), 6.10(m, 1H), 4.59(m, 1H), 3.80(m, 1H), 3.54(m, 1H), 3.15(m, 1H), 2.40(m, 10H), 2.13(s, 3H), 1.95(m, 3H), 1.78(m, 1H), 1.68(m, 2H), 1.53(m, 4H) | |||||
187 | 4-(hydroxy)piperidin-1-yl | R | 2 | chloro | c-Pen |
(500MHz, DMSO-d6); δ 11.48(brs, 1H), 6.79(s, 1H), 6.68(s, 1H), 6.16(s, 1H), 6.10(m, 1H), 4.60(m, 1H), 3.80(m, 1H), 3.54(m, 1H), 3.32(m, 4H), 3.16(m, 1H), 2.71(m 1H), 2.60(m, 1H), 2.32(m, 5H), 1.71(m, 5H), 1.57(m, 5H) | |||||
188 | 2-oxopiperazin-4-yl | R | 2 | chloro | c-Pen |
(500MHz, DMSO-d6); δ 11.48(br s, 1H), 7.71(s, 1H), 6.79(s, 1H), 6.68(s, 1H), 6.16(s, 1H), 6.10(m, 1H), 4.61(m, 1H), 3.81(m, 1H), 3.55(m, 1H), 3.13(m, 3H), 2.92(m, 2H), 2.56(m 3H), 1.96(m, 3H), 1.80(m, 1H), 1.68(m, 2H), 1.53(m, 4H) | |||||
189 | piperidin-1-yl | R | 2 | chloro | c-Pen |
(500MHz, DMSO-d6); δ 11.52(brs, 1H), 6.80(s, 1H), 6.70(s, 1H), 6.16(s, 1H), 6.12(m, 1H), 4.63(m, 1H), 3.80(m, 1H), 3.57(m, 1H), 3.29(m, 4H), 3.17(m, 1H), 2.60(m, 4H), 1.95(m, 3H), 1.68(m, 2H), 1.58(m, 9H) | |||||
190 | 1,1-dioxo-thiomorpholin-4-yl | R | 2 | chloro | c-Pen |
(500MHz, DMSO-d6); δ 11.48(brs, 1H), 6.79(s, 1H), 6.68(s, 1H), 6.16(s, 1H), 6.09(m, 1H), 4.61(m, 1H), 3.80(m, 1H), 3.56(m, 1H), 3.16(m, 1H), 3.07(m, 4H), 2.89(m, 4H), 2.67(m, 2H), 1.94(m, 3H), 1.81(m, 1H), 1.68(m, 2H), 1.53(m, 4H) | |||||
191 | 2-oxopyrrolidin-1-yl | R | 2 | chloro | c-Pen |
(500MHz, DMSO-d6); δ 11.49(brs, 1H), 6.80(s, 1H), 6.69(s, 1H), 6.16(s, 1H), 4.51(m, 1H), 3.80(m, 1H), 3.57(m, 1H), 3.46(m, 1H), 3.32(m, 1H), 3.15(m, 1H), 2.18(m, 2H), 1.91 (m, 5H), 1.80(m, 1H), 1.68(m, 2H), 1.53(m, 4H) | |||||
Reference Example 192 | (3S)-3-(dimethylaminocarboxy)pipe ridin-1-yl | R | 2 | chloro | THP-4-yl |
(400MHz, DMSO-d6); δ 11.48(s, 1H), 6.81 (s, 1H), 6.69(s, 1H), 6.28(s, 1H), 6.04(d, 1H), 4.60(q, 1H), 3.87(m, 2H), 3.56(m, 2H), 3.44(t, 2H), 3.16(m, 1H), 2.97(s, 3H), 2,95(m, 1H), 2.88-2.76(m, 2H), 2.74(m, 5H), 1.96(m, 4H), 1.80(m, 2H), 1.66(m, 2H), 1.50-1.37(m, 3H), 1.23(m, 1H) | |||||
Reference Example 193 | piperazin-1-yl | R | 2 | chloro | THP-4-yl |
(400MHz, DMSO-d6); δ 11.42(s, 1H), 6.83(s, 1H), 6.74(s, 1H), 6.30(s, 1H), 6.02(d, 1H), 4.69(m, 1H), 3.85(m, 1H), 3.52-3.42(m, 6H), 3.35(m, 3H), 3.20(m, 2H), 2.16(m, 2H), 1.92(m, 3H), 1.42(m, 3H) | |||||
Reference Example 194 | 1-(hydroxymethylcarbonyl) piperazin-4-yl | R | 2 | chloro | THP-4-yl |
(500MHz, DMSO-d6); δ 11.48(brs, 1H), 6.81(s, 1H), 6.69(d, J=1.8Hz, 1H), 6.29(s, 1H), 6.05(d, J=7.4Hz, 1H), 4.62(m, 1H), 4.49(t, 1H), 4.04(m, 2H), 3.87(m, 2H), 3.56(m, 1H), 3.45(m, 4H), 3.29(m, 4H), 3.16(m, 1H), 2.36(m, 4H), 1.96(m, 3H), 1.80(m, 1H), 1.40(m, 2H) | |||||
Reference Example 195 | 1-(trifluoroacetyl)piperazin-4-yl | R | 2 | chloro | THP-4-yl |
(500MHz, DMSO-d6); δ 11.47(s, 1H), 6.81(s, 1H), 6.69(s, 1H), 6.28(s, 1H), 6.09(d, 1H), 4.62(q, 1H), 3.87(m, 2H), 3.56(m, 4H), 3.47-3.38(m, 7H), 3.16(m, 1H), 2.53(m, 1H), 2.37∼2.30(m, 4H), 1.94(m, 3H), 1.81 (m, 1H), 1.40(m, 2H) | |||||
Reference Example 196 | 1-[(furan-2-yl)catbonyl] piperazin-4-yl | R | 2 | chloro | THP-4-yl |
(500MHz, DMSO-d6); δ 11.48(br s, 1H), 7.79(s, 1H), 6.81(s, 1H), 6.69(s, 1H), 6.59(m, 1H), 6.28(s, 1H), 6.05(m, 1H), 4.63(m, 1H), 3.86(m, 2H), 3.57(m, 6H), 3.44(m, 2H), 3.16(m, 2H), 2.56(m, 1H), 1.96(m, 3H), 1.83(m, 1H), 1.41(m, 2H) | |||||
Reference Example 197 | 1-(1,4-pyrazin-2-yl)piperazin -4-yl | R | 2 | chloro | THP-4-yl |
(500MHz, DM50-d6); δ 11.48(br s, 1H), 8.27(s, 1H), 8.04(s, 1H), 7.80(s, 1H), 6.81(s, 1H), 6.69(s, 1H), 6.29(s, 1H), 6.05(m, 1H), 4.64(m, 1H), 3.86(m, 2H), 3.57(m, 2H), 3.53(m, 4H), 3.18(m, 1H), 2.57(m, 1H), 1.99(m, 1H), 1.95(m, 2H), 1.83(m, 1H), 1.40(m, 2H) | |||||
Reference Example 198 | 1-(1,3-pyrazin-2-yl)piperazin -4-yl | R | 2 | chloro | THP-4-yl |
(500MHz, DMSO-d6); δ 11.49(brs, 1H), 8.31(m, 1H), 6.81(s, 1H), 6.69(s, 1H), 6.58(m, 1H), 6.28(s, 1H), 6.06(m, 1H), 4.65(m, 1H), 3.86(m, 2H), 3.69(m, 4H), 3.58(m, 2H), 3.45(m, 2H), 3.35(m, 1H), 3.18(m, 1H), 2.56(m, 1H). 2.43(m, 3H), 2.00(m, 1H), 1.96(m, 2H), 1.40(m, 2H) | |||||
199 | amino | R | 2 | fluoro | c-Pen |
(400MHz, CDCl3/DMSO-d6); δ 11.28(brs, 1H), 6.80(brs, 2H), 6.80(d, J=2.0Hz), 6.50(dd, 1H), 6.16(dd, 1H), 4.58(m, 1H), 3.81(m, 1H), 3.54(m, 1H), 3.24(m, 2H), 3.02(m, 1H), 2.13∼1.55(m, 10H) | |||||
200 | 1-(acetyl)piperazin-4-yl | R | 2 | fluoro | c-Pen |
(400MHz, CDCl3); δ 10.47(brs, 1H), 6.87(s, 1H), 6.66(d, J=8.0Hz, 1H), 6.26(d, J=12.0Hz. 1H), 4.80(m, 1H), 3.92(m, 1H), 3.81(m, 1H), 3.59(m, 2H), 3.49(m, 1H), 3.28(m, 1H), 3.18(m, 1H), 2.44(m, 2H), 2.34(m, 1H), 2.23(m, 2H), 2.14(m, 1H), 2.05(s, 3H), 1.93(m, 1H), 1.81(m, 1H), 1.71(m, 5H), 1.48(m, 2H) | |||||
201 | morpholin-4-yl | R | 2 | fluoro | c-Pen |
(400MHz, CDCl3); δ 10.92(brs, 1H), 6.87(s, 1H), 6.64(d, J=8.0Hz, 1H), 6.24(d, J=12.0Hz, 1H), 4.83(m, 1H), 3.93(m, 1H), 3.77(m, 1H), 3.54(m, 4H), 3.47(m, 1H), 3.17(m, 1H), 2.38(m, 1H), 2.33(m, 2H), 2.16(m, 2H), 2.04(m, 3H), 1.77(m, 1H), 1.65(m, 4H), 1.47(m, 1H), 1.35(m, 1H) | |||||
202 | dimethylamino | R | 2 | fluoro | c-Pen |
(400MHz, CDCl3);. δ10.99(br s, 1H), 6.80(s, 1H), 6.60(d, J=8.0Hz, 1H), 6.22(d, J=12.0Hz, 1H), 4.59(m, 1H), 4.13(m, 1H), 3.47(m, 1H), 3.03(m, 1H), 2.90(m, 1H), 2.55(m, 1H), 2.42(s, 6H), 2.01(m, 3H), 1.81(m, 1H), 1.62(m, 2H), 1.55(m, 4H) | |||||
203 | pyrrolidin-1-yl | R | 2 | fluoro | c-Pen |
(400MHz, CDCl3); δ 11.39(br s, 1H), 6.81(s, 1H), 6.63(dd, 1H), 6.25(dd, 1H), 4.59(m, 1H), 4.17(m, 1H), 3.89(m, 1H), 3.32(m, 1H), 3.07(m, 3H), 2.71(m, 1H), 2.09(m, 2H), 1.95(m, 4H), 1.77(m, 2H), 1.65(m, 4H) | |||||
204 | 1,1-dioxo-thiomorpholin-4-yl | R | 2 | fluoro | c-Pen |
(400MHz, CDCl3); δ 11.05(br s, 1H), 6.94(s, 1H), 6.60(d, J=8.0Hz, 1H), 6.26(d, J=12.0Hz, 1H), 4.74(m, 1H), 3.85(m, 1H), 3.62(t, 1H), 3.49(q, 1H), 3.18(q, 1H), 3.00(m, 8H), 2.74(m, 2H), 2.05(m, 3H), 1.79(m, 2H), 1.63(m, 4H) | |||||
205 | 2-oxopiperazin-4-yl | R | 2 | fluoro | c-Pen |
(400MHz, CDCl3); δ 11.26(br s, 1H), 7.26(br s, 1H), 6.87(s, 1H), 6.58(d, J=8.0Hz, 1H), 6.22(d, J=12.0Hz, 1H), 4.73(m, 1H), 3.84(m, 1H), 3.53(t, 1H), 3.19(m, 5H), 2.57(m, 4H), 2.04(m, 3H), 1.95(m, 1H), 1.74(m, 2H), 1.62(m, 2H) | |||||
206 | 1-(hydroxymethylcarbonyl) piperazin-4-yl | R | 2 | fluoro | c-Pen |
(400MHz, CDCl3); δ 11.26(br s, 1H), 6.89(s, 1H), 6.63(d, J=8.0Hz, 1H), 6.22(d, J=12.0Hz, 1H), 4.85(m, 1H), 4.10(s, 2H), 3.77(m, 1H), 3.57(m, 2H), 3.41(m, 1H), 3.14(q, 1H), 3.00(m, 1H), 2.91(m, 1H), 2.38(m, 3H), 2.12(m, 2H), 2.02(m, 4H), 1.85(m, 1H), 1.77(m, 1H), 1.63(m, 4H), 1.36(m, 1H), 1.26(m, 1H) | |||||
207 | methanesulfonyl | R | 2 | fluoro | c-Pen |
(400MHz, CDCl3); δ 9.89(br s, 1H), 6.87(s, 1H), 6.67(dd, 1H), 6.28(dd, 1H), 4.77(m, 1H), 3.83(t, 1H), 3.59(m, 1H), 3.31(m, 1H), 3.13(m, 2H), 2.84(s, 3H), 2.27(m, 2H), 2.04(m, 2H), 1.68(m, 6H), 1.51(m, 2H) | |||||
Reference Example 208 | dimethylamino | R | 2 | fluoro | THP-4-yl |
(400MHz, CDCl3); δ 11.27(br s, 1H), 6.79(s, 1H), 6.60(d, J=8.0Hz, 1H), 6.22(d, J=12.0Hz, 1H), 4.61(m, 1H), 4.13(m, 2H), 3.59(m, 4H), 3.04(m, 1H), 2.55(s, 4H), 2.04(m, 6H), 1.65(m, 2H), 1.26(m, 2H) | |||||
Reference Example 209 | pyrrolidin-1-yl | R | 2 | fluoro | THP-4-yl |
(400MHz, CDCl3); δ 11.16(br s, 1H), 6.87(s, 1H), 6.68(d, J=8.0Hz, 1H), 6.26(d, J=12.0Hz, 1H), 4.69(m, 1H), 4.17(d, J=8.0Hz, 2H), 3.60(m, 5H), 3.17(m, 1H), 2.90(m, 1H), 2.67(m, 5H), 2.09(m, 3H), 1.90(m, 4H), 1.57(m, 2H) | |||||
Reference 210 | morpholin-4-yl | R | 2 | fluoro | THP-4-yl |
(400MHz, CDCl3); δ 11.16(br s, 1H), 6.86(s, 1H), 6.64(d, J=8.0Hz, 1H), 6.23(d, J=12.0Hz, 1H), 4.75(m, 1H), 4.02(m, 1H), 3.66(m, 4H), 3.51(m, 4H), 3.18(m, 1H), 2.60(m, 1H), 2.49(m, 4H), 2.07(m, 4H), 1.80(m, 1H), 1.54(m, 2H) | |||||
Reference Example 211 | 1-(acetyl)piperazin-4-yl | R | 2 | fluoro | THP-4-yl |
(400MHz, CDCl3); δ 10.20(br s, 1H), 6.87(s, 1H), 6.68(d, J=8.0Hz, 1H), 6.27(d, J=12.0Hz, 1H), 4.76(m, 1H), 4.01(m, 3H), 3.61(m, 4H), 3.30(m, 2H), 3.20(m, 1H), 2.51(m, 2H), 2.33(m, 4H), 2.06(m, 7H), 1.99(m, 1H), 1.49(m, 2H) | |||||
Reference Example 212 | 1,1-dioxo-thiomorpholin-4-yl | R | 2 | fluoro | THP-4-yl |
(400MHz, CDCl3); δ 6.93(s, 1H), 6.64(d, J=8.0Hz, 1H), 6.28(d, J=12.0Hz, 1H), 4.68(m, 1H), 4.03(m, 2H), 3.55(m, 3H), 3.26(m, 2H), 3.17(m, 3H), 3.05(m, 4H), 2.95(m, 1H), 2.82(m, 1H), 2.09(m, 4H), 1.82(m, 1H), 1.65(m, 2H) | |||||
Reference Example 213 | methanesulfonyl | R | 2 | fluoro | THP-4-yl |
(400MHz, CDCl3); δ 10.15(br s, 1H), 6.86(s, 1H), 6.65(dd, 1H), 6.26(dd, 1H), 4.77(m, 1H), 4.05(m, 1H), 3.56(m, 4H), 3.36(m, 1H), 3.24(m, 2H), 3.12(m, 1H), 2.91(s, 3H), 2.32(m, 1H), 2.22(m, 1H), 2.133(m, 1H), 2.02(m, 1H), 1.54(m, 2H) | |||||
Reference Example 214 | 2-oxopiperazin-4-yl | R | 2 | fluoro | THP-4-yl |
(400MHz, CDCl3); δ 11.07(br s, 1H), 7.70(br s, 1H), 6.83(s, 1H), 6.61(d, J=8.0Hz, 1H), 6.22(d, J=12.0Hz, 1H), 5.19(m, 1H), 4.71(m, 1H), 4.05(d, J=12.0Hz, 2H), 3.55(m, 4H), 3.33(m, 3H), 3.14(m, 1H), 2.73(m, 4H), 2.10(m, 2H), 1.98(m, 2H), 1.58(m, 4H) | |||||
215 | 1-(hydroxymethylcarbonyl) piperazin-4-yl | R | 2 | fluoro | THP-4-yl |
(400MHz, CDCl3); δ 11.19(br s, 1H), 6.89(s, 1H), 6.65(d, J=8.0Hz, 1H), 6.23(d, J=12.0Hz, 1H), 4.82(m, 1H), 4.20(m, 1H), 4.18(s, 2H), 3.98(m, 2H), 3.61(m, 2H), 3.47(m, 4H), 3.16(m, 3H), 2.42(m, 3H), 2.17(m, 5H), 1.90(m, 2H), 1.40(m, 2H) | |||||
216 | dimethylamino | R | 2 | H | c-Pen |
(500MHz, DMSO-d6); δ 10.62(br s, 1H), 7.03(d, J=7.95Hz, 1H), 6.99(t, 1H), 6.93(s, 1H), 6.48(d, J=7.35Hz, 1H), 4.83(m, 1H), 3.83(m, 1H), 3.56(m, 1H), 3.46(m, 2H), 3.20(m, 4H), 2.05∼1.87(m, 4H), 1.70∼1.38(m, 6H) | |||||
217 | piperidin-1-yl | R | 2 | H | c-Pen |
(400MHz, CDCl3); δ 10.34(br s, 1H), 7.04(d, 1H), 6.99(t, 1H), 6.49(d, 1H), 4.72(m, 1H), 3.86(m, 1H), 3.51(m, 1H), 3.15(m, 1H), 2.30∼2.00(m, 8H), 2.69∼1.40(m, 14H) | |||||
Reference Example 218 | methanesulfonyl | R | 2 | H | THP-4-yl |
(400MHz, CDCl3); δ 10.02(br s, 1H), 7.08(d, 1H), 7.00(t, 1H), 6.95(s, 1H), 6.54(d, 1H), 4.78(m, 1H), 4.01(m, 2H), 3.61-3.47(m, 4H), 3.33(m, 1H), 3.15(m, 2H), 2.85(s, 3H), 2.25(m, 2H). 2.05(m, 2H), 1.51(m, 2H) | |||||
219 | 1-(hydroxymethylcarbonyl) piperazin-4-yl | R | 2 | methoxy | c-Pen |
(400MHz, CDCl3); δ 11.13(br s, 1H), 6.98(s, 1H), 6.42(s, 1H), 6.13(d, 1H), 4.85(m, 1H), 4.07(s, 2H), 3.81(m, 8H), 3.55(m, 2H), 3.39(m, 1H), 3.13(m, 1H), 2.96(m, 1H), 2.90(m, 1H), 2.35(m, 3H), 2.10(m, 2H), 1.99(m, 3H), 1.84(m, 1H), 1.75(m, 1H), 1.62(m, 4H), 1.44(m, 1H), 1.35(m, 1H) | |||||
220 | 1-(acetyl)piperazin-4-yl | R | 3 | chloro | c-Pen |
(400MHz, CDCl3); δ 10.33(br s, 1H), 6.97(s, 1H), 6.81(s, 1H), 6.42(s, 1H), 4.64(m, 1H), 3.85(m, 1H), 3.65(m, 2H), 3.56(m, 1H), 3.45(m, 2H), 3.13(m, 1H), 2.43(m, 6H), 2.04(m, 2H), 1.72(m, 8H), 1.54(m, 2H) | |||||
221 | morpholin-4-yl | R | 1 | H | c-Pen |
(400MHz, DMSO-d6); δ 11.37(br s, 1H), 6.83(m, 1H), 6.75(m, 1H), 6:29(d, J=8.0Hz, 1H), 5.85(d, J=8.0Hz, 1H), 4.87(m, 1H), 3.87(m, 1H), 3.61(m, 4H), 3.35(m, 3H), 2.71 (m, 1H), 2.54(m, 2H), 2.44(m, 2H), 1.99(m, 2H), 1.74(m, 6H), 1.59(m, 4H) | |||||
222 | morpholin-4-yl | R | 3 | chloro | c-Pen |
(400MHz, CDCl3); δ 11.07(br s, 1H), 6.90(s, 1H), 6.74(s, 1H), 6.36(s, 1H), 4.61(m, 1H), 3.94(m, 4H), 3.55(m, 1H), 3.04(m, 3H), 2.04(m, 7H), 1.71(m, 3H), 1.61(m, 4H), 1.26(m, 3H) | |||||
223 | dimethylamino | R | 1 | H | c-Pen |
(400MHz, CDCl3); δ 9.87(br, 1H), 7.05(d, J=8.0Hz, 1H), 6.99(t, 1H), 6.89(s, 1H), 6.52(d, J=8.0Hz, 1H), 4.83(m, 1H), 3.91(m, 1H), 3.50(t, 1H), 3.29(t, 1H), 2.63(m, 1H), 2.44(m, 1H), 2.29(s, 6H), 2.04(m, 2H), 1.70(m, 2H), 1.50(m, 4H | |||||
224 | morpholin-4-yl | R | 2 | chloro | c-Pen |
(DMSO-d6, ppm); δ 11.46(1H, s), 6.79(1H, s), 6.68(1H, s), 6.11(1H, s), 6.09(1H, d), 4.61(1H, quin), 3.81(1H, m), 3.57(4H, m), 3.15(1H, m), 2.50-2.43(3H, m), 2.35(4H, m), 1.95(2H, m), 1.80(1H, m), 1.68(2H, m), 1.57-1.49(4H, m),1.21(1H, m) |
Reference Example 225: {5-Methyl-2-[(R)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-oxazol-2-yl]-1H-indol-7yl}-(tetrahydropyran-4-yl)-amine
Reference Example 226: {5-Methyl-2-[(S)-4-(2-morpholin-4-yl-ethyl)-45-dihydro-thiazol-2-yl]-1H-indol-7-yl}-(tetrahydro-pyran-4-ylmethyl)-amine
Step A: ((S)-2-{5-methyl-7-[(tetrahydro-pyran-4-ylmethyl)-amino]-1H-indol-2-yl}-4,5-dihydro-thiazol-4-yl)-acetic acid isopropyl ester
Step B: 2-((R)-2-{5-methyl-7-[(terahydro-pyran-4-ylmetyl)-amino]-1H-indol-2-yl}-4,5-dihydro-thiazol-4-yl)-ethanol
Step C: {5-Methyl-2-[(S)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-(tetrahydro-pyran-4-ylmethyl)-amine
Examples 227 to 257:
Example | R1 | * | n | R2 | R3 | R4 |
H1 NMR data | ||||||
Reference Example 227 | 1-(acetyl)piperazin-4-yl | S | 2 | pheno xy | isob utyl | isobutyl |
(400MHz, CDCl3); δ 9.56 (1H, brs), 7.30-7.24 (2H, m), 7.04-7.00 (1H, m), 6.96-6.94 (3H, m), 6.84 (1H, d, J=2.4Hz), 6.63 (1H, d, J=2.0Hz), 4.79-4.72 (1H, m), 3.64-3.52 (3H, m), 3.45-3.34 (2H, m), 3.17-3.00 (5H, m), 2.64-2.52 (2H, m), 2.44-2.35 (1H, m), 2.08 (1H, s), 2.06-1.99 (1H, m), 1.91-1.82 (1H, m), 1.50-1.40 (2H, m), 1.38-1.26 (4H, m), 0.82-0.79 (12H, m) | ||||||
Reference Example 228 | pyrrolidin-1-yl | S | 2 | pheno xy | isob utyl | isobutyl |
(400MHz, CDCl3); δ 9.24 (1H, brs), 7.31-7.27 (2H, m), 7.05-7.02 (1H, m), 6.97-6.95 (3H, m), 6.86 (1H, d, J=2.0Hz), 6.68 (1H, d, J=2.0Hz), 4.77-4.70 (1H, m), 3.63-3.58 (1H, m), 3.41-3.28 (6H, m), 3.19-3.05 (5H, m), 2.52-2.46 (1H, m), 2.26-2.20 (1H, m), 2.16-2.13 (4H, m), 1.56-1.46 (2H, m), 1.38-1.33 (4H, m), 0.85-0.83 (12H, m) | ||||||
229 | 1-(hydroxymethylcarbo nyl)piperazin-4-yl | S | 2 | pheno xy | H | c-Pen |
(400MHz, CDCl3); δ 10.7 (1H, brs), 7.30-7.27 (2H, m), 7.04-6.97 (3H, m), 6.86 (1H, s), 6.62 (1H, d, J=2.0Hz), 6.28 (1H, d, J=2.5Hz), 4.87-4.80 (1H, m), 3.80-3.75 (1H, m), 3.59-3.55 (2H, m), 3.49-3.45 (1H, m), 3.18-3.08 (2H, m), 3.03-3.01 (1H, m), 2.47-2.38 (3H, m), 2.24-2.14 (3H, m), 2.05-1.88 (4H, m), 1.84-1.55 (8H, m), 1.49-1.39 (2H, m) | ||||||
230 | piperazin-1-yl | S | 2 | phenoxy | H | c-Pen |
(400MHz, CDCl3); δ 7.40-7.36 (4H, m), 7.16-7.12 (1H, m), 7.04-7.02 (2H, m), 6.94 (1H, s), 4.20-4.15 (1H, m), 3.99-3.94 (1H, m), 3.91-3.80 (5H, m), 3.75-3.63 (6H, m), 3.58-3.48 (1H, m), 2.44-2.40 (2H, m), 2.09-2.07 (2H, m), 1.91-1.89 (4H, m), 1.71-1.69 (2H, m) | ||||||
231 | 1-BOC-piperazin-4-yl | S | 2 | pheno xy | H | c-Pen |
(400MHz, CDCl3); δ 10.7(1H, s), 7.30-7.26 (2H, m), 7.03-6.98 (3H, m), 6.85 (1H, s), 6.62 (1H, d, J=2.0 Hz), 6.26 (1H, d, J=2.4 Hz), 4.82-4.77 (1H, m), 3.87 (1H, brs), 3.78-3.74 (1H, m), 3.59-3.54 (1H, m), 3.31 (4H, brs), 3.19-3.14 (1H, m), 2.48-2.35 (2H, m), 2.26 (1H, brs), 2.17 (1H, brs), 2.03-1.91 (4H, m), 1.84-1.75 (1H, m), 1.67-1.53 (4H, m), 1.45 (9H, s), 1.42-1.35 (1H, m) | ||||||
232 |
|
S | 2 | pheno xy | H | c-Pen |
(400MHz, CDCl3); δ 10.9 (1H, brs), 7.32-7.28 (2H, m), 7.05-6.99 (3H, m), 6.90 (1H, s), 6.59 (1H, d, J=1.6 Hz), 6.29 (1H, d, J=2.0 Hz), 4.77-4.74 (1H, m), 4.06-3.99 (1H, m), 3.95-3.82 (4H, m), 3.62-3.57 (1H, m), 3.18-3.14 (1H, m), 2.87-2.80 (3H, m), 2.77-2.74 (1H, m), 2.00-1.98 (4H, m), 1.69 (2H, brs), 1.60-1.56 (6H, m) | ||||||
233 | 2-oxopiperazin-4-yl | S | pheno xy | H | c-Pen | |
(400MHz, CDCl3); δ 10.7 (1H, brs), 7.30-7.26 (2H, m), 7.03-7.00 (3H, m), 6.82 (1H, s), 6.60 (1H, d, J=2.0 Hz), 3.25 (1H, d, J=2.0 Hz), 4.74-4.71 (2H, m), 3.83 (1H, brs), 3.56-3.52 (1H, m), 3.50-3.26 (2H, m), 3.20-3.10 (2H, m), 2.68-2.61 (4H, m), 2.01-1.86 (4H, m), 1.73-1.58 (8H, m) | ||||||
234 | 1-[(tetrahydrofuran-2-yl)carbonyl] piperazin-4-yl | S | pheno xy | H | c-Pen | |
(400MHz, CDCl3); δ 10.67-10.58 (1H, m), 7.30-7.27 (2H, m), 7.04-6.98 (m, 3H), 6.85 (1H, d, J=1.2Hz), 6.62 (1H, d, J=2.0Hz), 6.27 (1H, brs), 4.84-4.78 (1H, m), 4.58-4.54 (m, 1H), 3.96-3.91 (1H, m), 3.87-3.71 (3H, m), 3.59-3.42 (3H, m), 3.19-3.14 (1H, m), 2.47-2.37 (2H, m), 2.33-2.16 (4H, m), 2.07-1.87 (6H, m), 1.83-1.75 (4H, m), 1.68-1.56 (1H, m), 1.49-1.40 (2H, m) | ||||||
235 | 1-(pyridin-2-yl)piperazin-4-yl | S | 2 | pheno xy | H | c-Pen |
(400MHz, CDCl3); δ 10.3 (1H, s), 8.19-8.18 (1H, m), 7.49-7.45 (1H, m), 7.29-7.25 (2H, m), 7.03-6.98 (3H, m), 6.85 (1H, s), 6.64-6.60 (3H, m), 6.28 (1H, d, J=2.4 Hz), 4.82-4.78 (1H, m), 3.79 (1H, brs), 3.60-3.55 (1H, m), 3.49-3.45 (4H, m), 3.21-3.17 (1H, m), 2.55-2.41 (6H, m), 1.99 (3H, brs), 1.88-1.86 (1H, m), 1.70 (3H, brs), 1.61-1.47 (3H, m) | ||||||
236 | 1-(2-fluorophenyl) piperazin-4-yl | S | 2 | pheno xy | H | c-Pen |
(400MHz, CDCl3); δ 10.7 (1H, s), 7.29-7.25 (2H, m), 7.07-6.98 (5H, m), 6.95-6.88 (2H,m), 6.86 (1H, s), 6.23 (1H, d, J=1.6Hz), 6.28(1H, d, J=1.6Hz), 4.88-4.81 (1H, m), 3.89 (1H, brs), 3.60-3.56 (1H, m), 3.23-3.18 (1H, m), 2.99 (4H, brs), 2.54-2.43 (5H, m), 2.04-1.94 (3H, m), 1.98-1.82 (2H, m), 1.68-1.37 (6H, m) | ||||||
237 | 2-oxopiperazin-4-yl | S | 2 | H | H | c-Pen |
(400MHz, CDCl3); δ 10.23 (brs, 1H), 7.00 (m, 2H), 6.89 (s, 1H), 6.48 (s, 1H), 4.72 (m, 1H), 3.92 (m, 1H), 3.54 (m, 1H), 3.38-3.11 (m, 5H), 2.73-2.58 (m, 4H), 2.11-1.96 (m, 4H), 1.74-1.55 (m, 6) | ||||||
238 | (3S)-3-(amino) pyrrolidin-1-yl | S | 2 | pheno xy | H | c-Pen |
(400Hz, CDCl3); δ 9.97(br s, 1H), 7.32(m, 1H), 7.01-6.95(m, 6H), 6.93(m, 3H), 6.69(s, 1H), 6.34(m, 1H), 4.83(m, 1H), 3.85(m, 1H), 3.62(dd, 1H), 3.24(dd, 1H), 3.10(m, 4H), 2.58(m, 6H), 2.05(m, 3H), 1.92(m, 1H), 1.70(m, 6H), 1.53(m, 2H) | ||||||
239 | 1-(acetyl)piperazin-4-yl | S | 2 | pheno xy | H | c-Pen |
(400MHz, CDCl3); δ 10.6 (1H, s), 7.31-7.27 (2H, m), 7.04-6.98 (3H, m), 6.84 (1H, s), 6.60 (1H, d, J=2.0 Hz), 6.27 (1H, d, J=1.6 Hz), 4.77-4.72 (1H, m), 4.30 (1H, brs), 3.81 (1H, brs), 3.74 (1H, brs), 3.64-3.55 (2H, m), 3.41 (1H, brs), 3.17-3.10 (2H, m), 2.89 (1H, brs), 2.68-2.63 (3H, m), 2.56-2.48 (2H, m), 2.06 (3H, s), 2.03-1.90 (4H, m), 1.72 (2H, brs), 1.60-1.56 (4H, m) | ||||||
Reference Example 240 | (2R)-2-(aminocarbonyl)pyrrolidin-1-yl | S | 2 | methyl | H | (THP-4-yl)methyl |
(CDCl3, 400MHz) δ 11.31 (s, 1H), 8.18 (br, 1H), 7.24 (d, 1H), 6.83 (s, 1H), 6.75 (s, 1H), 6.22 (s, 1H), 5.50 (br, 1H), 4.71-4.64 (m, 1H), 4.07-3.99 (m, 2H), 3.57-3.38 (m, 3H), 3.28-3.25 (m, 1H), 3.19-3.06 (m, 4H), 2.88-2.81 (m, 1H), 2.75-2.70 (m, 1H), 2.49-2.41 (m, 1H), 2.39 (s, 3H) 2.25-2.12 (m, 1H), 2.08-2.04 (m, 1H), 1.99-1.95 (m, 2H), 1.83-1.80 (m, 4H), 1.53-1.40 (m, 2H) | ||||||
Reference Example 241 | (2R)-2-(hydroxylmethyl)pyrr olidim-1-yl | S | 2 | methyl | H | (THP-4-yl)methyl |
(CDCl3, 400MHz) δ 10.25 (s, 1H), 6.76 (s, 1H), 6.74 (s, 1H), 6.23 (s, 1H), 4.67-4.58 (m, 2H), 4:16-4.0 (m, 1H), 4.00-3.94 (m, 2H), 3.73-3.68 (m, 1H), 3.50-3.36 (m, 2H), 3.11 (d, 2H), 2.99-2.94 (m, 2H), 2.32 (s, 3H), 2.15-2.07 (m, 2H), 2.02-1.92 (m, 3H), 1.76-1.73 (m, 2H), 1.42-1.36 (m, 2H), 1.14-1.08 (m, 2H), 0.86-0.81 (m, 2H), 0.73-0.68 (m, 2H) | ||||||
242 | (3R)-3-(acetylamino) pyrrolidin-1-yl | S | 2 | pheno xy | H | c-Pen |
(500Hz, CDCl3)1 δ 11.45(br s, 1H), 8.14(br s, 1H), 6.90(s, 1H), 6.77(s, 1H), 6.37(s, 1H), 4.83(m, 1H), 4.66(m, 1H), 4.05(m, 1H), 3.91(m, 1H), 3.77(m, 1H), 3.62-3.52(m, 2H), 3.13(m, 1H), 3.08-3.00(m, 2H), 2.84(m, 1H), 2.43(m, 1H), 2.23(m, 1H), 2.05(m, 4H), 2.00(s, 3H), 1.80(m, 2H), 1.71(m, 2H), 1.63(m, 2H) | ||||||
243 | 4-(benzyl)piperazin-1-yl | S | 2 | pheno xy | H | c-Pen |
(500Hz, CDCl3); δ 7.32-724(m, 7H), 7.01(m, 3H), 6.77(s, 1H), 6.59(s, 1H), 6.29(s, 1H), 4.71(m, 1H), 3.87(m, 1H), 3.56(dd, 1H), 3.50(s, 2H), 3.08(dd, 1H), 2.80(br s, 8H), 2.60(br s, 2H), 2.11-1.99(m, 4H), 1.80(m, 2H), 1.71(m, 2H), 1.61(m, 2H) | ||||||
Reference Example 244 |
|
S | 2 | methyl | H | (THP-4-yl)methyl |
(400MHz, CDCl3)§ δ 10.08(s, 1H), 6.82(s, 1H), 6.80(s, 1H), 6.29(s, 1H), 4.66(s, 1H), 4.10-3.90(m, 6H), 3.52(dd, 1H), 3.40(m, 2H), 3.10(m, 2H), 2.39(s, 3H), 2.10-1.95(m, 3H), 2.95-2.85(m, 2H), 2.72(d, 2H), 1.42-1.30(m, 2H), 1.25(q, 6H) | ||||||
Reference Example 245 | morpholin-4-yl | S | 2 | methyl | H | (THP-4-yl)methyl |
(500MHz, CDCl3)1 δ 11.13 (s, 1H), 6.84 (s, 1H), 6.81 (s, 1H), 6.24 (s, 1H), 4.81-4.78 (m, 1H), 3.87 (d, 2H), 3.60-3.46 (m, 5H), 3.35-3.30 (m, 2H), 3.19-3.17 (m, 1H), 3.01 (br, 2H), 2.38-2.36 (m, 7H), 2.14 (br, 2H), 1.91-1.88 (m, 1H), 1.75-1.71 (m, 2H), 1.28-1.21 (m, 2H) | ||||||
246 | pyrrolidin-1-yl | R | 2 | pheno xy | H | c-Pen |
(500MHz, CDCl3); δ 7.26-7.23 (2H, m), 6.98-6.95 (1H, m), 6.91-6.90 (2H, m), 6.74 (1H, s), 6.46-6.45 (1H, m), 6.12 (1H, brs), 4.60-4.58 (1H, m), 3.82-3.80 (2H, m), 3.60-3.50 (2H, m), 3.33-3.28 (5H, m), 3.14-3.10 (1H, m), 2.14-2.03 (6H, m), 2.00-1.94 (2H, m), 1.78 (2H, brs), 1.66-1.60 (4H, m) | ||||||
Reference example 247 | morpholin-4-yl | S | 2 | pheno xy | H | (THP-4-yl)methyl |
(400MHz, CDCl3); δ 10.19 (brs, 1H), 7.29 (m, 2H), 7.01 (m, 3H), 6.84(d, 1H), 6.65(d, 1H), 6.27(d, 1H), 4.77(m, 1H), 3.93(m, 2H), 3.83(m, 1H), 3.63-3.55(m, 6H), 3.35(m, 6H), 3.19(m, 1H), 3.04(m, 2H), 2.46 (m, 2H), 2.34(m, 4H), 2.00(m, 1H), 1.83(m, 2H), 1.60(m, 2H), 1.30(m, 2H) | ||||||
Reference example 248 | 2-oxopiperazin-4-yl | S | 2 | pheno xy | H | (THP-4-yl)methyl |
(400MHz, CDCl3); δ 10.7 (brs, 1H), 7.28 (m, 2H), 7.00(m, 3H), 6.85(brs, 1H), 6.81(d, 1H), 6.60(d, J= 1.6 Hz, 1H), 6.20(d, J=2.0 Hz, 1H), 5.03(m, 1H), 4.70(m, 1H), 3.98(m, 2H), 3.56(m, 1H), 3.49-3.36(m, 6H), 3.15-3.06(m, 4H), 2.80 (m, 1H), 2.71(m, 3H), 1.95-1.91(m, 3H), 1.72(m, 2H), 1.42(m, 2H). | ||||||
249 | pyrrolidin-1-yl | S | 2 | pheno xy | H | c-Pen |
(500MHz, CDCl3); δ 7.31-7.27 (2H, m), 7.03-7.00 (1H, m), 6.96-6.94 (2H, m), 6.50 (1H, d, J=2.0Hz), 6.17 (1H, d, J=2.0Hz), 4.73-4.66 (1H, m), 3.86 (brs, 1H), 3.74-3.58 (2H, m), 3.46-3.37 (4, m), 3.23-3.19 (1H, m), 2.24-2.10 (6, m), 2.10-1.80 (2H, m), 1.70-1.65 (5H m) | ||||||
250 | 2-oxopiperazin-4-yl | S | 2 | methyl | H | 4,4-difluorocyclohexane |
(400MHz, CDCl3); δ 10.14 (brs, 1H), 6.82 (s, 1H), 6.80 (s, 1H), 6.31 (s, 1H), 4.65 (m, 1H), 3.54 (m,1H), 3.53 (dd, J=8Hz, 1H), 3.39 (m, 2H), 3.30 (m, 1H), 3.22-3.08 (m, 4H), 2.78-2.65 (m, 4H), 2.38 (s, 3H), 2.28-2.04 (m, 4H), 1.96-1.86 (m, 2H), 1.73 (m, 2H) | ||||||
251 | morpholin-4-yl | S | 2 | methyl | H | 4,4-difluorocyclohexane |
(400MHz, CDCl3); δ 9.67 (brs, 1H), 6.87(s, 1H), 6.82(s, 1H), 6.34 (s, 1H), 4.71 (m, 1H), 3.65(m, 6H), 3.55 (dd, J=8Hz, 1H), 3.51(m, 1H), 3.15(dd, J=8Hz, 1H), 2.52-2.29(m, 9H), 2.15-2.04(m, 4H), 1.96-1.90(m, 2H), 1.58-1.51(m, 2H) | ||||||
Reference example 252 |
|
S | 2 | methyl | H | (THP-4-yl)methyl |
(500MHz, CDCl3); δ 9.47(br s, 1H), 6.88(s, 1H), 6.47(s, 1H), 6.39(s, 1H), 5.87(br s, 1H), 4.12-4.00(m, 2H), 3.85(br s, 4H), 3.66(m, 1H), 3.58(t, 2H), 3.08(br s, 4H), 2.95(m, 1H), 2.85-2.70(m, 3H), 2.41(s, 3H), 2.10(m, 2H), 1.96(m, 2H), 1.60(m, 2H) | ||||||
Reference example 253 | 2-oxopiperazin-4-yl | S | 2 | methyl | H | (THP-4-yl)methyl |
(500MHz, CDCl3); δ 11.03(s, 1H), 8.19(br s, 1H), 6.82(s, 1H), 6.79(s, 1H), 6.31(s, 1H), 4.84-4.65(m, 3H), 4.24(m, 1H), 3.91(m, 2H), 3.82-3.55(m, 4H), 3.31(m, 2H), 3.19(m, 1H), 3.14(m, 2H), 2.95(m, 2H), 2.69(m, 1H), 2.20(m, 1H), 1.98(m, 1H), 1.81 (d, 2H), 1.39(m, 2H) | ||||||
Reference example 254 | 1-(pyridin-2-yl)piperazin-4-yl | S | 2 | chloro | H | THP-4-yl |
(400MHz, CDCl3); δ 9.71 (brs, 1H), 8.17 (s, 1H), 7.47 (m, 1H), 7.03 (s, 1H), 6.82 (s, 1H), 6.62 (m, 1H), 6.45 (s, 1H), 4.73 (m, 1H), 4.01 (m, 2H), 3.61-3.49 (m, 8H), 3.20 (m, 1H), 2.69-2.50 (m, 6H), 2.11-2.01 (m, 3H), 1.92 (m, 1H), 1.52 (m, 2H) | ||||||
Reference Example 255 | 1-[(tetrahydrofuran-2-yl)carbonyl] piperazin-4-yl | S | 2 | chloro | H | THP-4-yl |
(400MHz, CDCl3); δ 9.89 (brs, 1H), 7.02 (s, 1H), 6.82 (s, 1H), 6.45 (s, 1H), 4.73 (m, 1H), 4.57 (m, 1H), 4.01 (m, 2H), 3.94 (m, 1H), 3.85 (m, 1H), 3.78-3.49 (m, 8H), 3.15 (m, 2H), 2.64-2.21 (m, 7H), 2.11-1.81 (m, 7H), 1.48 (m, 1H) | ||||||
Reference Example 256 | 2-oxopiperazin-4-yl | R | 2 | metho xy | H | THP-4-yl |
(400MHz, CDCl3); δ 10.75(br s, 1H), 7.02(br s, 1H), 6.83(s, 1H), 6.41(s, 1H), 6.14(s, 1H), 4.70(m, 1H), 4.01(d, J=12Hz, 2H), 3.58(s, 3H), 3.54(m, 4H), 3.11∼3.36(m, 5H), 2.66(m, 4H), 2.12(m, 2H), 1.97(m, 1H), 1.88(m, 1H), 1.56(m, 2H) | ||||||
Reference Example 257 | 1-(hydroxymethylcarbo nyl)piperazin-4-yl | R | 2 | metho xy | H | THP-4-yl |
(400MHz, CDCl3); δ 11.13(br s, 1H), 6.91(s, 1H), 6.47(s, 1H), 6.17(s, 1H), 4.86(m, 1H), 4.13(m, 2H), 3.97(m, 3H), 3.84(m, 3H), 3.62(m, 2H), 3.47(m, 4H), 3.03(m, 3H), 2.43(m, 3H), 2.17(m, 5H), 1.98(m, 3H), 1.44(m, 2H) |
Example 258: [(R)-2-(5-aminomethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol
Example 259: Furan-2-carboxylic acid [7-cyclopentylamino-2-((R)-4-hydroxymethyl-4,5-dihydro-thiazol-2-yl)-1H-indol-5-ylmethyl]-amide
Example 260: [(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-ylmethoxy]-acetic acid methyl ester
Example 261: [(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-ylmethoxy]-acetic acid
Example 262: Cyclopentyl-{2-[(R)-4-(3-cyclopentyl-[1,2,4]oxadiazol-5-ylmethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine
Example 263: Cylopentyl-{2-[(R)-4-(3-piperidin-1-yl-[1,2,4]oxadiazol-5-ylmethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine
Experimental Example 1: Measurements and analysis of the Example compounds for the hepatocyte protective effect against the substances deriving hepatocyte toxicity.
Cell protective effect of the compound of Example 4 against the substances deriving hepatotoxicity | |||
Substances deriving hepatocyte toxicity | Treatment concentration | EC50 (µM) | Note on the substances deriving hepatocyte toxicity |
Terfenadine | 10 µM | 0.4 | Anti-allergic drug |
Simvastatin | 16 µM | < 10 uM | Lipid-lowering drug |
Diclofenac | 350 µM | 40% viability at 3-100 uM | Nonsteroidal anti-inflammatory drug (NSAID) |
Adefovir | 100 µM | 50% viability at 3-30 uM | Anti-viral drug |
Cell protective effects against doxorubicin in hepatocytes | |||||||
Example | EC50, uM | Example | EC50, uM | Example | EC50, uM | Example | EC50, uM |
1 | >1 | 38 | 2.0 | 109 | 0.61 | 229 | 0.25 |
2 | 0.1 | 40 | 15.58 | 115 | <1 | 230 | >0.32 |
4 | 0.3 | 43 * | 1~10 | 117 | <0.5 | 231 | 0.2 |
6 | 4.93 | 45 | 1.32 | 118 * | 0.41 | 232 | 0.24 |
7 * | 1.17 | 46 | 0.4 | 119 | 0.17 | 233 | 0.27 |
8 * | 0.41 | 47 | 0.36 | 120 * | 1.12 | 234 | 0.09 |
9 * | >2 | 48 | 0.2 | 121 | 0.47 | 235 | >0.54 |
10 * | 0.6 | 50 | 0.25 | 122 * | 0.96 | 236 | 0.16 |
11 * | 2.8 | 51 * | 0.6 | 127 * | 1.18 | 237 | 0.2 |
12 * | 3.25 | 52 * | 0.75 | 128 | 0.2 | 238 | 0.33 |
13 * | 1.13 | 61 | 0.78 | 130 | 0.1 | 239 | 0.83 |
14 | 0.19 | 62 * | 3.77 | 133 | 0.31 | 240 * | 0.28 |
15 * | 0.6 | 64 | 0.54 | 134 | 0.51 | 241 * | 0.21 |
16 * | 1.29 | 67 * | >1 | 135 * | 1.26 | 244 * | 0.195 |
17 | 0.315 | 68 | 0.49 | 158 | 0.91 | 246 | 0.35 |
18 * | 2.42 | 71 | 1.1 | 173 | 1.98 | 247 * | 0.86 |
19 | 0.35 | 78 * | 29.44 | 176 | >1 | 249 | 0.11 |
20 * | 5.77 | 83 | 0.6 | 177 | >1 | 250 | 0.09 |
21 | 0.3 | 84 | 1.6 | 178 | 0.23 | 251 | 0.3 |
22 * | 0.25 | 85 | 0.4 | 182 * | 0.375 | 252 * | 0.51 |
23 | 0.14 | 88 | 1.87 | 184 * | 0.18 | 253 * | 0.2 |
24 * | 0.13 | 90 * | 7.92 | 193 * | 0.65 | 254 * | 1.0 |
25 * | 0.76 | 93 * | 0.55 | 201 | 0.33 | 257 | <0.4 |
26 | 0.2 | 94 | 28.14 | 205 | 0.34 | ||
32 * | 2.12 | 97 | 4.1 | 218 * | 0.26 | ||
33 | 4.04 | 101 | 1∼10 | 222 | 0.18 | ||
34 | 5.58 | 108 | <0.5 | 228 | 0.13 |
* Reference Example |
Experimental Example 2: Protective effects when tBHP (tert-Butyl Hydroxy Peroxide; t-BuOOH) was treated on hepatocytes and other cells derived from various tissues
1) Protective effect when tBHP was treated on primary hepatocytes
2) Protective effect when tBHP was treated on pancreatic cells (Linm5F)
3) Protective effect when tBHP was treated on cardiac cells (H9C2, white rat cardiomyocyte)
4) Protective effect when tBHP was treated on kidney cells (LLC-PK1)
5) Protective effect when tBHP was treated on chondrocytes
6) Protective effect when tBHP was treated on brain cells (SK-N-MC)
[Industrial Applicability]
n denotes a number of 0 to 3,
A represents 5 membered heteroaryl or heterocycle each of which has 1 to 3 hetero atoms selected from N, O and S,
R1 represents R5-X-B-X'-,
B represents a direct bond, or represents 3∼10 membered heterocycle or heteroaryl each of which has 1 to 4 hetero atoms selected from N, O and S,
X and X' independently of one another represent a direct bond, or are selected from the group consisting of -NR6-, -CO-, -CONR6-, -CO2-, -OC(O)-, -S(O)m-, -O-(CH2)m-, -(CH2)m-O-, -(CH2)m-, -NR6CO-, -(R6O)2P(O)- and -NHCO2-, wherein m denotes a number of 0 to 3, and R6 represents hydrogen, alkyl or cycloalkyl,
R5 represents hydrogen, nitrile, hydroxy, alkyl, alkoxy, cycloalkyl or aryl, or represents 3∼10 membered monocyclic or fused cyclic heterocycle or heteroaryl each of which has 1 to 3 hetero atoms selected from N, O and S, and is optionally substituted by oxo or alkyl, or
R5 and R6 may together form a 4∼8 membered cycle,
R2 represents -(CR8R9)p-Y-R7,
p denotes a number of 0 to 2,
R8 and R9 independently of one another represent hydrogen or alkyl, or may together form a 4∼8 membered cycle,
Y represents a direct bond, or is selected from the group consisting of -O-, -S-, -NR6-, -NR6C(O)-, -CO2-, -C(O)-, -C(O)NR6-, -S(O)q-, and -S(O)qNR6-, wherein q denotes a number of 0 to 2,
R7 represents hydrogen, halogen, cyano, hydroxy, nitro, alkyl, cycloalkyl or aryl, or represents 3∼10 membered heterocycle or heteroaryl each of which has 1 to 3 hetero atoms selected from N, S and O and which optionally contains oxo,
R3 represents hydrogen, alkyl, -(CH2)q-cycloalkyl or -(CH2)q-heterocycle,
R4 represents cycloalkyl, optically containing oxo,
where alkyl, alkoxy, aryl, cycloalkyl, heterocycle and heteroaryl may be optionally substituted, and the substituents are one or more selected from the group consisting of hydroxy, halogen, nitrile, amino, alkylamino, dialkylamino, alkyl, haloalkyl, alkylsulfonyl, carboxyalkyl, alkylcarbonyloxy, alkylthio, alkyloxycarbonyl, alkylaminocarbonyl, arylalkoxy and oxo, and pharmaceutically acceptable salts or optical isomer (R or S isomer), racemate, mixture of diastereomers, or individual diastereomer thereof.n and R1 are as defined in Claim 2, and
R represents hydrogen, or represents C1-C4-alkyl optionally substituted by hydroxy or amino.
Cyclopentyl-[2-(4,5-dihydro-1,3-thiazol-2-yl)-1H-indol-7-yl]-amine;
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-4-yl]-methanol;
[(R)-2-(5-chloro-7-cyclopentylamino-1H-i-ndol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;
[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;
(R)-2-[7-cyclopentylamino-5-(hydroxymethyl)-1H-indol-2-yl]-4,5-dihydrothiazol-4-yl-methanol;
[(S)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic
acid;
[(S)-2-(5-methyl-7-(4,4-difluorocyclohexan-4-yl)amino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(S)-2-(5-methyl-7-cyclobutylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(S)-2-(5-methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-4-yl]-methanol;
[(R)-2-(5-(dimethylamino)methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-(pyrrol-3-yl)methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-methanol;
[(R)-2-(5-(1,3-imidazol-1-yl)methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-(pyrazo]-1-yl)methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-methanol;
[(R)-2-(5-acetylamino-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-phenoxymethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acetic acid;
[(R)-2-(5-(pyrrolidin-1-yl)methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;
Cyclopentyl-[5-chloro-2-((R)-4-isobutyl-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl)-amine;
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid ethyl ester;
Cyclopentyl-[5-fluoro-2-((R)-4-ethyl-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl]-amine;
{(R)-2-[7-(methyl-cyclopentyl)amino-5-fluoro-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-4-yl}-methanol;
[(S)-2-(5-ethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;
[(S)-2-(5-ethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(S)-2-(5-ethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;
[(R)-2-(5-methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-carboxylic acid ethyl ester;
[(S)-2-(5-phenoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;
[(R)-2-(5-bromo-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-(pyridin3-yl)oxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-methanol;
[(R)-2-(5-methanesulflonylmethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-(isoindol-1,3-dion-2-yl)methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-bromo-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid ethyl ester;
[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid ethyl ester;
[(R)-2-(5-methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;
[(R)-2-(5-methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-ethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-propyloxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-phenoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-(pyridin-3-yl)oxy-7-cyclopentylamino-1H-1-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acetic acid methyl ester;
[(R)-2-(5-(pyridin-3-yl)oxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acetic acid;
[(R)-2-(5-methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;
[(R)-2-(5-methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-(4-(methanesulfonyl)phenoxy)-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-phenoxymethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acetic acid methyl ester;
[(R)-2-(5-phenylaminomethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acetic acid methyl ester;
[(R)-2-(5-methanesulfonylmethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid methyl ester;
[(R)-2-(5-methanesulfonylmethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-acetic acid;
[(R)-2-(5-methanesulfonylmethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl acetamide;
3-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;
[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propanol;
3-[(R)-2-(5-methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]propionic acid ethyl ester;
3-[(R)-2-(5-methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;
3-[(R)-2-(5-phenoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;
3-[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid ethyl ester;
3-[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;
3-[(R)-2-(5-bromo-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid ethyl ester;
3-[(R)-2-(5-bromo-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;
3-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;
3-[(R)-2-(5-methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;
3-[(R)-2-(5-ethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid ethyl ester;
3-[(R)-2-(5-ethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionic acid;
3-[(R)-2-(5-trifluoromethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionic acid ethyl ester;
3-[(R)-2-(5-trifluoromethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionic acid;
[(S)-2-(5-methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-oxazol-4-yl]-acetic acid;
[(S)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-oxazol-4-yl]-acetic acid;
[2-((4S,5R)-5-aminomethyl-4-benzyl-dihydro-oxazol-2-yl)-5-chloro-1H-indol-7-yl]-cyclopentyl-amine;
{2-[(R)-5-((S)-1-amino-2-phenyl-ethyl)-4,5-dihydro-oxazol-2-yl]-5-chloro-1H-indol-7-yl}-cyclopentyl-amine;
Cyclopentyl-[2-(4,5-dihydro-oxadiazol-2-yl)-1H-indol-7-yl]-amine;
[2-(5-Methyl-7-cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-methanol;
[2-(5-Methyl-7-cyclopentylamino-1H-indol-2-yl)-thiazol-5-yl]-methanol;
[2-(5-Methyl-7-cyclopentylantino-1H-indol-2-yl)-thiazol-4-yl]-carboxylic acid
ethyl ester;
[2-(5-Methyl-7-cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-carboxylic acid;
[2-(7-Cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-methanol;
[2-(7-Cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-carboxylic acid methyl
ester;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-morpholin-4-yl-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)ethylamino-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)propylamino-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-methylamino-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-dimethylamino-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-[4-(methyl)piperazin-1-yl]-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(3-dimethylaminopyrrolidin-1-yl)-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(piperidin-4-yl)-ethanone;
2-[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(4-(methyl)piperazin-1-yl)-ethanone;
2-[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)ethylamino-ethanone;
2-[(R)-2-(5-methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(methylamino)-4-yl-ethanone;
2-[(R)-2-(5-methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)-ethanone;
2-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-methylamino-ethanone;
2-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)ethylamino-ethanone;
2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(4-(methyl)piperazin-1-yl)-ethanone;
Cyclopentyl-{5-methanesulfonylmethyl-2-[(R)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl} -amine;
1-(4-{2-[(R)-2-(7-cyclopentylamino-5-methanesulfonylmethyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl} -piperazin-1-yl)-ethanone;
Cyclopentyl-[2-((R)-4-pyrrolidin-1-ylmethyl-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl]-amine;
{5-Chloro-2-[(R)-4-(2-dimethylamino-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine;
{5-Chloro-2-[(R)-4-(2-piperazin-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine;
(5-Chloro-2- {(R)-4-[2-(4-ethanesulfonyl-piperazin-1-yl)-ethyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
1-(4-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanone;
{5-Chloro-2-[(R)-4-(2-pyrazol-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine;
(S)-1-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-pyrrolidine-2-carboxylic acid;
{5-Chloro-2-[(R)-4-(2-methanesulfonyl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amine;
3-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-5-methyl-3H-imidazole-4-carboxylic acid ethyl ester;
3-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-5-methyl-3H-imidazole-4-carboxylic acid;
Cyclopentyl-{2-[(R)-4-(2-methoxy-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine;
[2-((R)-4-aminomethyl-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl]-cyclopentylamine;
{2-[(R)-4-((R)-3-amino-pyrrolidin-1-ylethyl)-4,5-dihydro-thiazol-2-yl]-5-chloro-1H-indol-7-yl}-cyclopentyl-amine;
4-[(R)-2-(7-cyclopentylamino-5-ethoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-ylethyl]-piperazin-2-one;
{2-[(R)-4-((S)-3-amino-pyrrolidin-1-ylethyl)-4,5-dihydro-thiazol-2-yl]-5-chloro-1H-indol-7-yl}-cyclopentyl-amine;
(5-Chloro-2-{(S)-4-[2-(3-dimethylamino-phenyl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
1-(4-{2-[(S)-2-(7-cyclopentylamino-5-chloro-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanone;
1-(4-{2-[(S)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperain-1-yl)-ethanone;
(5-Methoxy-2-{(R)-4-[2-(pyrrolidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Methanesulfonylmethyl-2-{(S)-4-[(2-oxopiperazin-4-yl)-ethyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
1-(4-{2-[(R)-2-(7-cyclopentylamino-5-chloro-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanone;
(5-Chloro-2-{(R)-4-[4-methyl-piperazin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Chloro-2-{(R)-4-[4-(hydroxy)piperidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Chloro-2-{(R)-4-[2-oxopiperazin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Chloro-2-{(R)-4-[(piperidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Chloro-2-{(R)-4-[(1,1-dioxo-thiomorpholin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Chloro-2-{(R)-4-[(2-oxopyrrolidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Fluoro-2-{(R)-4-(2-aminoethyl)-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
1-(4-{2-[(R)-2-(5-fluoro-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanone;
(5-Fluoro-2-{(R)-4-[(morpholin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Fluoro-2-{(R)-4-(2-dimethylamino-ethyl)4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Fluoro-2-{R)-4-[(pyrrolidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Fluoro-2-{(R)-4-[(1,1-dioxo-thiomorpholin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Fluoro-2-{(R)-4-(2-oxopyrrolidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
1-(4-{2-[(5-Fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]ethyl}-piperazin-1-yl)-2-hydroxy-ethanone;
(5-Fluoro-2-{(R)-4-[methanesulfonyl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(2-{(R)-4-[2-dimethylamino-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(2-{(R)-4-[(piperidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
1-(4-{2-[(R)-2-(5-methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanone;
1-(4-{2-[(R)-2-(7-cyclopentylamino)-5-chloro-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propyl}-piperazin-1-yl)-ethanone;
2-{(R)-4-[(morpholin-4-yl)-methyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Chloro-2-{(R)-4-[(morpholin-4-yl)-propyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(2-{(R)-4-[2-dimethylamino-methyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Chloro-2-{(S)-4-[(morpholin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
1-(4-{2-[(S)-2-(5-phenoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanone;
(5-Phenoxy-2-{(S)-4-[(piperazin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
t-Butyl-(4-{2-[(S)-2-(5-phenoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazine-1-carboxylate;
Cyclopentyl-(5-phenoxy-2-{(S)-4-[2-(3-fluoromethyl-5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-amine;
(5-Phenoxy-2-{(S)-4-[2-oxopiperazin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(4-{2-[(S)-2-(5-phenoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-oxoran-2-yl-methanone;
(5-Phenoxy-2-{(S)-4-[(pyridin-2-yl)piperazine-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Phenoxy-2-{(S)-4-[{2-fluorophenyl)piperazine-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Chloro-2-{(S)-4-[2-oxopiperazin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Phenoxy-2-{(S)-4-[(3S)-3-(amino)pyrrolidin-1-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
1-(4-{2-[(S)-2-(5-phenoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanone;
(5-Chloro-[(S)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl])-pyrrolidin-3-yl-acetamide;
(5-Phenoxy-2-{(S)-4-[4-(benzyl)piperazin-1-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Phenoxy-2-{(R)-4-[pyrrolidin-1-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Phenoxy-2-{(S)-4-[pyrrolidin-1-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amine;
(5-Methyl-2-{(S)-4-[2-oxopiperazin-4-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1 H-indol-7-yl)-4,4-difluorocyclohexyl-amine;
(5-Methyl-2-{(S)-4-[morpholin-4-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-4,4-difluorocyclohexyl-amine;
1-(4-{2-[(R)-2-(5-methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanone;
[(R)-2-(5-aminomethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
Furan-2-carboxylic acid (7-cyclopentylamino-2-((R)-4-hydroxymethyl-4,5-dihydro-thiazol-2-yl)-1H-indo1-5-ylmethyl]-amide;
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-ylmethoxy]-acetic acid methyl ester;
[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-ylmethoxy]-acetic acid;
Cyclopentyl-{2-[(R)-4-(3-cyclopentyl-[1,2,4]oxadiazol-5-ylmethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amine; and
Cyclopentyl-{2-[(R)-4-(3-piperidin-1-yl-[1,2,4]oxadiazol-5-ylmethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl} -amine.
n eine Zahl von 0 bis 3 bedeutet,
A 5-gliedriges/n Heteroaryl oder Heterozyklus repräsentiert, jeweils mit 1 bis 3 Heteroatomen, ausgewählt aus N, O und S,
R1 R5-X-B-X'- repräsentiert,
B eine Direktbindung repräsentiert oder 3-10-gliedrigen/s Heterozyklus oder Heteroaryl jeweils mit 1 bis 4 Heteroatomen repräsentiert, die aus N, O und S ausgewählt sind,
X und X' unabhängig voneinander eine Direktbindung repräsentieren oder ausgewählt sind aus der Gruppe bestehend aus -NR6-, -CO-, -CONR6-, -CO2-, -OC(O)-, -S(O)m-, -O-(CH2)m-, -(CH2)m-O-, -(CH2)m-, -NR6CO-, -(R6O)2P(O)- und -NHCO2-, wobei m eine Zahl von 0 bis 3 bedeutet und R6 Wasserstoff, Alkyl oder Cycloalkyl repräsentiert,
R5 Wasserstoff, Nitril, Hydroxy, Alkyl, Alkoxy, Cycloalkyl oder Aryl repräsentiert oder 3-10-gliedrigen/s monocyclischen/s oder kondensierten/s zyklischen/s Heterozyklus oder Heteroaryl jeweils mit 1 bis 3 Heteroatomen repräsentiert, die aus N, O und S ausgewählt sind, optional substituiert durch Oxo oder Alkyl, oder
R5 und R6 zusammen einen 4-8-gliedrigen Zyklus bilden können,
R2 -(CR8R9)p-Y-R7 repräsentiert,
p eine Zahl von 0 bis 2 bedeutet,
R8 und R9 unabhängig voneinander Wasserstoff oder Alkyl repräsentieren oder zusammen einen 4-8-gliedrigen Zyklus bilden können,
Y eine Direktbindung repräsentiert oder ausgewählt ist aus der Gruppe bestehend aus -O-, -S-, -NR6-, -NR6C(O)-, -CO2-, -C(O)-, -C(O)NR6-, -S(O)q- und - S(O)qNR6-, wobei q eine Zahl von 0 bis 2 bedeutet,
R7 Wasserstoff, Halogen, Cyano, Hydroxy, Nitro, Alkyl, Cycloalkyl oder Aryl repräsentiert oder 3-10-gliedrigen/s Heterozyklus oder Heteroaryl mit 1 bis 3 Heteroatomen repräsentiert, die aus N, O und S ausgewählt sind, das optional Oxo enthält,
R3 Wasserstoff, Alkyl, -(CH2)q-Cycloalkyl oder -(CH2)q-Heterozyklus repräsentiert,
R4 Cycloalkyl repräsentiert, das optional Oxo enthält,
wobei Alkyl, Alkoxy, Aryl, Cycloalkyl, Heterozyklus und Heteroaryl optional substituiert sein können und die Substituenten einer oder mehrere sind, ausgewählt aus der Gruppe bestehend aus Hydroxy, Halogen, Nitril, Amino, Alkylamino, Dialkylamino, Alkyl, Haloalkyl, Alkylsulfonyl, Carboxyalkyl, Alkylcarbonyloxy, Alkylthio, Alkyloxycarbonyl, Alkylaminocarbonyl, Arylalkoxy und Oxo, und pharmazeutisch akzeptable Salze oder ein optisches Isomer (R- oder S-Isomer), Racemat, ein Gemisch von Diastereomeren oder individuellem Diastereomer davon.n und R1 wie in Anspruch 2 definiert sind, und
R Wasserstoff repräsentiert oder C1-C4-Alkyl repräsentiert, optional substituiert durch Hydroxy oder Amino.
Cyclopentyl-[2-(4,5-dihydro-1,3-thiazol-2-yl)-1 H-indol-7-yl]-amin;
[(R)-2-(7-Cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-1,3-thiazol-4-yl]-methanol;
[(R)-2-(5-Chlor-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäuremethylester;
[(R)-2-(5-Chlor-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäure;
2-[(R)-2-(5-Chlor-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;
(R)-2-[7-Cyclopentylamino-5-(hydroxymethyl)-1 H-indol-2-yl]-4,5-dihydro-thiazol-4-yl-methanol;
[(S)-2-(7-Cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäure;
[(S)-2-(5-Methyl-7-(4,4-difluorcyclohexan-4-yl)amino-1 H-indol-2-yl]-4,5-dihydrothiazol-4-yl-essigsäure;
[(S)-2-(5-Methyl-7-cyclobutylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäure;
[(S)-2-(5-Methyl-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäure;
[(R)-2-(7-Cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-1,3-thiazol-4-yl]-methanol;
[(R)-2-(5-(Dimethylamino)methyl-7-Cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-(Pyrrol-3-yl)methyl-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-methanol;
[(R)-2-(5-(1,3-Imidazol-1-yl)methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-(Pyrazol-1-yl)methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-methanol;
[(R)-2-(5-Acetylamino-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-Phenoxymethyl-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäure;
[(R)-2-(5-Pyrrolidin-1-yl)methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-essigsäuremethylester;
Cyclopentyl-[5-chlor-2-((R)-4-isobutyl-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl]-amin;
[(R)-2-(7-Cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionsäureethylester;
Cyclopentyl-[5-fluor-2-((R)-4-ethyl-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl]-amin;
{(R)-2-(7-Methyl-cyclopentyl)amino-5-fluor-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-4-yl}-methanol ;
[(S)-2-(5-Ethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäuremethylester;
[(S)-2-(5-Ethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäure;
[(S)-2-(5-Ethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;
[(R)-2-(5-Methyl-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-carbonsäureethylester;
[(S)-2-(5-Phenoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäure;
[(R)-2-(5-Fluor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-Chlor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;
[(R)-2-(5-Brom-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-Methoxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-(Pyridin-3-yl)oxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-methanol;
[(R)-2-(5-Methansulfonylmethyl-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-methanol;
[(R)-2-(5-(Isoindol-1,3-dion-2-yl)methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
[(R)-2-(5-Brom-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäure;
[(R)-2-(5-Fluor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäure;
[(R)-2-(5-Fluor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäureethylester;
[(R)-2-(5-Fluor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethanol;
[(R)-2-(7-Cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäure;
[(R)-2-(7-Cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäureethylester;
[(R)-2-(5-Methoxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäuremethylester;
[(R)-2-(5-Methoxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäure;
[(R)-2-(5-Ethoxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäure;
[(R)-2-(5-Propyloxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäure;
[(R)-2-(5-Phenoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäure;
[(R)-2-(5-(Pyridin-3-yl)oxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-essigsäuremethylester;
[(R)-2-(5-(Pyridin-3-yl)oxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-essigsäure;
[(R)-2-(5-Methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäuremethylester;
[(R)-2-(5-Methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäure;
[(R)-2-(5-(4-(Methansulfonyl)phenoxy)-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäure;
[(R)-2-(5-Phenoxymethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-essigsäuremethylester;
[(R)-2-(5-Phenylaminomethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-essigsäuremethylester;
[(R)-2-(5-Methansulfonylmethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-essigsäuremethylester;
[(R)-2-(5-Methansulfonylmethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-essigsäure;
[(R)-2-(5-Methansulfonylmethyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethanol;
[(R)-2-(7-Cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethylacetamid;
3-[(R)-2-(5-Chlor-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionsäure;
[(R)-2-(5-Chlor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propanol;
3-[(R)-2-(5-Methyl-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionsäureethylester;
3-[(R)-2-(5-Methyl-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionsäure;
3-[(R)-2-(5-Phenoxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionsäure;
3-[(R)-2-(5-Fluor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionsäureethylester;
3-[(R)-2-(5-Fluor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionsäure;
3-[(R)-2-(5-Brom-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionsäureethylester;
3-[(R)-2-(5-Brom-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionsäure;
3-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionsäure;
3-[(R)-2-(5-Methoxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionsäure;
3-[(R)-2-(5-Ethoxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionsäureethylester;
3-[(R)-2-(5-Ethoxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propionsäure;
3-[(R)-2-(5-Trifluormethoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionsäureethylester;
3-[(R)-2-(5-Trifluormethoxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionsäure;
[(S)-2-(5-Methyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-oxazol-4-yl]-essigsäure;
[(S)-2-(5-Chlor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-oxazol-4-yl]-essigsäure;
[2-((4S,5R)-5-Aminomethyl-4-benzyl-dihydro-oxazol-2-yl)-5-chlor-1H-indol-7-yl)-cyclopentyl-amin;
{2-[(R)-5-((S)-1-Amino-2-phenyl-ethyl)-4,5-dihydro-oxazol-2-yl]-5-chlor-1H-indol-7-yl}cyclopentyl-amin;
Cyclopentyl-[2-(4,5-dihydro-oxadiazol-2-yl)-1H-indol-7-yl]-amin;
[2-(5-Methyl-7-cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-methanol;
[2-(5-Methyl-7-cyclopentylamino-1H-indol-2-yl)-thiazol-5-yl]-methanol;
[2-(5-Methyl-7-cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-carbonsäureethylester;
[2-(5-Methyl-7-cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-carbonsäure;
[2-(7-Cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-methanol;
[2-(7-Cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-carbonsäuremethylester;
2-[(R)-2-(5-Chlor-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-morpholin-4-yl-ethanon;
2-[(R)-2-(5-Chlor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)-ethylamino-ethanon;
2-[(R)-2-(5-Chlor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)-propylamino-ethanon;
2-[(R)-2-(5-Chlor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-methylamino-ethanon;
2-[(R)-2-(5-Chlor-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-dimethylamino-ethanon;
2-[(R)-2-(5-Chlor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-[4-(methyl)piperazin-1-yl]-ethanon;
2-[(R)-2-(5-Chlor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(3-dimethylaminopyrrolidin-1-yl)-ethanon;
2-[(R)-2-(5-Chlor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(piperidin-4-yl)-ethanon;
2-[(R)-2-(5-Fluor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(4-(methyl)piperazin-1-yl)-ethanon;
2-[(R)-2-(5-Fluor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)-ethylamino-ethanon;
2-[(R)-2-(5-Methoxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(methylamino)-4-yl-ethanon;
2-[(R)-2-(5-Methoxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)-ethanon;
2-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-methylamino-ethanon;
2-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)-ethanon;
2-[(R)-2-(5-Chlor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(morpholin-4-yl)ethylamino-ethanon;
2-[(R)-2-(5-Chlor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-1-(4-(methyl)piperazin-1-yl)-ethanon;
Cyclopentyl-{5-methansulfonylmethyl-2-[(R)-4-(2-morpholin-4-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1 H-indol-7-yl}-amin;
1-(4-{2-[(R)-2-(7-Cyclopentylamino-5-methansulfonylmethyl-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanon;
Cyclopentyl-[2-((R)-4-pyrrolidin-1-ylmethyl-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl]-amin;
{5-Chlor-2-[(R)-4-(2-dimethylamino-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amin;
{5-Chlor-2-[(R)-4-(2-piperazin-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amin;
(5-Chlor-2-{(R)-4-[2-(4-ethansulfonyl-piperazin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
1-(4-{2-[(R)-2-(5-Chlor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanon;
{5-Chlor-2-[(R)-4-(2-pyrazol-1-yl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amin;
(S)-1-{2-[(R)-2-(5-Chlor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-pyrrolidin-2-carbonsäure;
{5-Chlor-2-[(R)-4-(2-methansulfonyl-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-cyclopentyl-amin;
3-{2-[(R)-2-(5-Chlor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-5-methyl-3H-imidazol-4-carbonsäureethylester;
3-{2-[(R)-2-(5-Chlor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-5-methyl-3H-imidazol-4-carbonsäure;
Cyclopentyl-{2-[(R)-4-(2-methoxy-ethyl)-4,5-dihydro-thiazol-2-yl]-1H-indol-7-yl}-amin;
[2-((R)-4-Aminomethyl-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl]-cyclopentyl-amin;
{2-[(R)-4-((R)-3-Amino-pyrrolidin-1-ylethyl)-4,5-dihydro-thiazol-2-yl]-5-chlor-1H-indol-7-yl}-cyclopentyl-amin;
4[(R)-2-(7-Cyclopentylamino-5-ethoxy-1H-indol-2-yl)-4,5-dihydro-thiazol-4-ylethyl]-piperazin-2-on;
{2-[(R)-4-((S)-3-Amino-pyrrolidin-1-ylethyl)-4,5-dihydro-thiazol-2-yl]-5-chlor-1H-indol-7-yl}-cyclopentyl-amin;
(5-Chlor-2-{(S)-4-[2-(3-dimethylamino-phenyl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
1-(4-{2-[(S)-2-(7-Cyclopentylamino-5-chlor-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanon;
1-(4-{2-[(S)-2-(7-Cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanon;
(5-Methoxy-2-{(R)-4-[2-(pyrrolidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(5-Methansulfonylmethyl-2-{(S)-4-[2-oxopiperazin-4-yl)-ethyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
1-(4-{2-[(R)-2-(7-Cyclopentylamino-5-chlor-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanon;
(5-Chlor-2-{(R)-4-[4-methyl-piprazin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(5-Chlor-2-{(R)-4-[4-(hydroxy)piperidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(5-Chlor-2-{(R)-4-[2-oxopiperazin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(5-Chlor-2-{(R)-4-[(piperidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(5-Chlor-2-{(R)-4-[(1,1-dioxo-thiomorpholin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1 H-indol-7-yl)-cyclopentyl-amin;
(5-Chlor-2-{(R)-4-[(2-oxopyrrolidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(5-Fluor-2-{(R)-4-(2-aminoethyl)-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
1-(4-{2-[(R)-2-(5-Fluor-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanon;
(5-Fluor-2-{(R)-4-[(morpholin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(5-Fluor-2-{(R)-4-(2-dimethylamino-ethyl)-4,5-dihydro-thiazo1-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(5-Fluor-2-{(R)-4-[(pyrrolidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(5-Fluor-2-{(R)-4-[(1,1-dioxo-thiomorpholin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl-1H-indol-7-yl)-cyclopentyl-amin;
(5-Fluor-2-{(R)-4-[(2-oxopyrrolidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
1-(4-{2-[(5-Fluor-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanon;
(5-Fluor-2-{(R)-4-[methansulfonyl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(2-{(R)-4-[2-Dimethylamino-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(2-{(R)-4-[(Piperidin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
1-(4-{2-[(R)-2-(5-Methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanon;
1-(4-{2-[(R)-2-(7-cyclopentylamino)-5-chlor-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-propyl}-piperazin-1-yl)-ethanon;
2-{(R)-4-[(Morpholin-4-yl)-methyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(5-Chlor-2-{(R)-4-[(morpholin-4-yl)-propyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(2-{(R)-4-[2-Dimethylamino-methyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(5-Chlor-2-{(S)-4-[(morpholin-4-yl)-ethyl]-4,5-dihydro-thiazo1-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
1-(4-{2-[(S)-2-(5-Phenoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanon;
(5-Phenoxy-2-{(S)-4-[(piperazin-1-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
t-Butyl-(4-{2-[(S)-2-(5-phenoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-carboxylat;
Cyclopentyl-(5-phenoxy-2-{(S)-4-[2-(3-fluormethyl-5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-amin;
(5-Phenoxy-2-{(S)-4-[2-oxopiperazin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(4-{2-[(S)-2-(5-Phenoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-oxoran-2-yl-methanon;
(5-Phenoxy-2-{(S)-4-[(pyridin-2-yl)piperazin-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(5-Phenoxy-2-{(S)-4-[(2-fluorphenyl)piperazin-ethyl]-4,5-dihydro-thiazol-2-yl)-1H-indol-7-yl)-cyclopentyl-amin;
(5-Chlor-2-{(S)-4-[2-oxopiperazin-4-yl)-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(5-Phenoxy-2-{(S)-4-[(3S)-3-(amino)pyrrolidin-1-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
1-(4-{2-[(S)-2-(5-Phenoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-ethyl}-piperazin-1-yl)-ethanon;
(5-Chlor-[(S)-2-(7-cyclopentylamino-1 H-indol-2-yl}-4,5-dihydro-thiazol-4-yl])-pyrrolidin-3-yl-acetamid;
(5-Phenoxy-2-{(S)-4-[4-(benzyl)piperazin-1-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(5-Phenoxy-2-{(R)-4-[pyrrolidin-1-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(5-Phenoxy-2-{(S)-4-[pyrrolidin-1-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-cyclopentyl-amin;
(5-Methyl-2-{(S)-4-[2-oxopiperazin-4-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-4,4-difluorcyclohexyl-amin;
(5-Methyl-2-{(S)-4-[morpholin-4-yl-ethyl]-4,5-dihydro-thiazol-2-yl}-1H-indol-7-yl)-4,4-difluorcyclohexyl-amin;
1-(4-{2-[(R)-2-(5-Methoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-ethyl}-piperazin-1-yl)-2-hydroxy-ethanon;
[(R)-2-(5-Aminomethyl-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-thiazol-4-yl]-methanol;
Furan-2-carbonsäure [7-cyclopentylamino-2-((R)-4-hydroxymethyl-4,5-dihydrothiazol-2-yl)-1 H-indol-5-ylmethyl]-amid;
[(R)-2-(7-Cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-ylmethoxy]-essigsäuremethylester;
[(R)-2-(7-Cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-thiazol-4-ylmethoxy]-essigsäure;
Cyclopentyl-{2-[(R)-4-(3-cyclopentyl-[1,2,4]oxadiazol-5-ylmethyl)-4,5-dihydrothiazol-2-yl]-1H-indol-7-yl}amin; und
Cyclopentyl-{2-[(R)-4-(3-piperidin-1-yl-[1,2,4]oxadiazol-5-ylmethyl)-4,5-dihydrothiazol-2-yl]-1H-indol-7-yl}-amin.
n désigne un nombre entre 0 et 3,
A représente un hétéroaryle ou un hétérocycle à 5 chaînons ayant chacun 1 à 3 hétéroatomes choisis parmi N, O et S,
R1 représente R5-X-B-X'-,
B représente une liaison directe ou représente un hétérocycle ou un hétéroaryle à 3 à 10 chaînons ayant chacun 1 à 4 hétéroatomes choisis parmi N, O et S,
X et X' représentent indépendamment l'un de l'autre une liaison directe ou sont choisis dans le groupe constitué par -NR6-, -CO-, -CONR6-, -CO2-, -OC(O)-, -S(O)m-, - O-(CH2)m-, -(CH2)m-O-, -(CH2)m-, -NR6CO-, -(R6O)2P(O)- et -NHCO2-, où m désigne un nombre entre 0 et 3, et R6 représente de l'hydrogène, de l'alkyle ou du cycloalkyle,
R5 représente de l'hydrogène, du nitrile, de l'hydroxy, de l'alkyle, de l'alcoxy, du cycloalkyle ou de l'aryle ou représente un hétérocycle ou hétéroaryle cyclique fusionné ou monocyclique à 3 à 10 chaînons ayant chacun 1 à 3 hétéroatomes choisis parmi N, O et S, et est facultativement substitué par de l'oxo ou de l'alkyle, ou
R5 et R6 peuvent former conjointement un cycle à 4 à 8 chaînons,
R2 représente -(CR8R9)p-Y-R7,
p désigne un nombre entre 0 et 2,
R8 et R9 représentent indépendamment l'un de l'autre de l'hydrogène ou un alkyle, ou peuvent former conjointement un cycle à 4 à 8 chaînons,
Y représente une liaison directe ou est choisi dans le groupe constitué par -O-, -S-, -NR6-, -NR6C(O)-, -CO2-, -C(O)-, -C(O)NR6-, S(O)q- et -S(O)qNR6-, où q désigne un nombre entre 0 et 2,
R7 représente de l'hydrogène, de l'halogène, du cyano, de l'hydroxy, du nitro, de l'alkyle, du cycloalkyle ou de l'aryle ou représente un hétérocycle ou hétéroaryle à 3 à 10 chaînons ayant chacun 1 à 3 hétéroatomes choisis parmi N, O et S, et contenant facultativement de l'oxo,
R3 représente de l'hydrogène, de l'alkyle, du -(CH2)q-cycloalkyle ou un -(CH2)q-hétérocycle,
R4 représente du cycloalkyle contenant facultativement de l'oxo,
où l'alkyle, l'alcoxy, l'aryle, le cycloalkyle, l'hétérocycle et l'hétéroaryle peuvent être facultativement substitués, et les substituants sont un ou plusieurs substituants choisis dans le groupe constitué par l'hydroxy, l'halogène, le nitrile, l'amino, l'alkylamino, le dialkylamino, l'alkyle, l'haloalkyle, l'alkylsulfonyle, le carboxyalkyle, l'alkylcarbonyloxy, l'alkylthio, l'alkyloxycarbonyle, l'alkylaminocarbonyle, l'arylalcoxy et l'oxo, et leurs sels ou leurs isomères optiques (isomères R ou S), racémates, mélanges de diastéréomères ou diastéréomères individuels pharmaceutiquement acceptables.n et R1 sont tels que définis dans la revendication 2, et
R représente de l'hydrogène ou représente de l'alkyle en C1 à C4 facultativement substitué par de l'hydroxy ou de l'amino.
la [2-(4,5-dihydro-1,3-thiazol-2-yl)-1H-indol-7-yl]-cyclopentylamine ;
le [(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-4-yl]-méthanol ;
l'ester méthylique d'acide [(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'acide [(R)-2-(5-chloro-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
le 2-[(R)-2-(5-chloro-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthanol ;
le (R)-2-[7-cyclopentylamino-5-(hydroxyméthyl)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-méthanol ;
l'acide [(S)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'acide [(S)-2-(5-méthyl-7-(4,4-difluorocyclohexan-4-yl)amino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'acide [(S)-2-(5-méthyl-7-cyclobutylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'acide [(S)-2-(5-méthyl-7-cyclopentylamino-1H-indol-2-yl)-4 ,5-d ihydrothiazol-4-yl]-acétique ;
le [(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-4-yl]-méthanol ;
le [(R)-2-(5-(diméthylamino)méthyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-méthanol ;
le [(R)-2-(5-(pyrrol-3-yl)méthyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-méthanol ;
le [(R)-2-(5-(1,3-imidazol-1-yl)méthyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-méthanol ;
le [(R)-2-(5-(pyrazol-1-yl)méthyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-méthanol ;
le [(R)-2-(5-acétylamino-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-méthanol ;
l'acide [(R)-2-(5-phénoxyméthyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'ester méthylique d'acide [(R)-2-(5-pyrrolidin-1-yl)-méthyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
la [5-chloro-2-((R)-4-isobutyl-4,5-dihydrothiazol-2-yl)-1H-indol-7-yl]-cyclopentylamine ;
l'ester éthylique d'acide [(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionique ;
la [5-fluoro-2-((R)-4-éthyl-4,5-dihydrothiazol-2-yl)-1H-indol-7-yl]-cyclopentylamine ;
le {(R)-2-[7-(méthylcyclopentyl)amino-5-fluoro-1H-indol-2-yl]-4,5-dihydro-1,3-thiazol-4-yl}-méthanol ;
l'ester méthylique d'acide [(S)-2-(5-éthoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'acide [(S)-2-(5-éthoxy-7-cyclopentylamino-1H-indol-2-yl)-4 ,5-d ihyd roth iazol-4-yl]-acétique ;
le [(S)-2-(5-éthoxy-7-cyclopentylamino-1H-indol-2-yl)-4 ,5-d ihyd roth iazol-4-yl]-éthanol ;
l'ester éthylique d'acide [(R)-2-(5-méthyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-carboxylique ;
l'acide [(S)-2-(5-phénoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
le [(R)-2-(5-fluoro-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-méthanol ;
le [(R)-2-(5-chloro-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthanol ;
le [(R)-2-(5-bromo-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-méthanol ;
le [(R)-2-(5-méthoxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-méthanol ;
le [(R)-2-(5-(pyridin-3-yl)oxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-méthanol ;
le [(R)-2-(5-méthanesulfonylméthyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-méthanol ;
le [(R)-2-(5-(isoindol-1,3-dion-2-yl)méthyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-méthanol ;
l'acide [(R)-2-(5-bromo-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'acide [(R)-2-(5-fluoro-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'ester éthylique d'acide [(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
le [(R)-2-(5-fluoro-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthanol ;
l'acide [(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'ester éthylique d'acide [(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'ester méthylique d'acide [(R)-2-(5-méthoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'acide [(R)-2-(5-méthoxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'acide [(R)-2-(5-éthoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-d ihyd roth iazol-4-yl]-acétique ;
l'acide [(R)-2-(5-propyloxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'acide [(R)-2-(5-phénoxy-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'ester méthylique d'acide [(R)-2-(5-(pyridine-3-yl)oxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'acide [(R)-2-(5-(pyridine-3-yl)oxy-7-cyclopentylamino-1H-indol-2-yl)-4 ,5-dihydrothiazol-4-yl]-acétique ;
l'ester méthylique d'acide [(R)-2-(5-méthyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'acide [(R)-2-(5-méthyl-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'acide [(R)-2-(5-(4-méthanesulfonyl)phénoxy)-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'ester méthylique d'acide [(R)-2-(5-phénoxyméthyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'ester méthylique d'acide [(R)-2-(5-phénylaminométhyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'ester méthylique d'acide [(R)-2-(5-méthanesulfonylméthyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
l'acide [(R)-2-(5-méthanesulfonylméthyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-acétique ;
le [(R)-2-(5-méthanesulfonylméthyl-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthanol ;
le [(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthylacétamide ;
l'acide 3-[(R)-2-(5-chloro-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionique ;
le [(R)-2-(5-chloro-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propanol ;
l'ester éthylique d'acide 3-[(R)-2-(5-méthyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionique ;
l'acide 3-[(R)-2-(5-méthyl-7-cyclopentylamino-1H-indol-2-yl)-4 ,5-d ihyd roth iazol-4-yl]-propionique ;
l'acide 3-[(R)-2-(5-phénoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionique ;
l'ester éthylique d'acide 3-[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionique ;
l'acide 3-[(R)-2-(5-fluoro-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionique;
l'ester éthylique d'acide 3-[(R)-2-(5-bromo-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionique ;
l'acide 3-[(R)-2-(5-bromo-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionique ;
l'acide 3-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionique;
l'acide 3-[(R)-2-(5-méthoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionique;
l'ester éthylique d'acide 3-[(R)-2-(5-éthoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionique ;
l'acide 3-[(R)-2-(5-éthoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionique ;
l'ester éthylique d'acide 3-[(R)-2-(5-trifluorométhoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionique ;
l'acide 3-[(R)-2-(5-trifluorométhoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propionique ;
l'acide [(S)-2-(5-méthyl-7-cyclopentylamino-1 H-indol-2-yl)-4,5-dihydro-oxazol-4-yl]-acétique ;
l'acide [(S)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydro-oxazol-4-yl]-acétique ;
la [2-((4S,5R)-5-aminométhyl-4-benzyl-dihydro-oxazol-2-yl)-5-chloro-1H-indol-7-yl]-cyclopentylamine ;
la {2-[(R)-5-((S)-1-amino-2-phényléthyl)-4,5-dihydro-oxazol-2-yl]-5-chloro-1H-indol-7-yl}-cyclopentylamine ;
la [2-(4,5-dihydro-oxadiazol-2-yl)-1H-indol-7-yl]-cyclopentylamine ;
le [2-(5-méthyl-7-cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]méthanol;
le [2-(5-méthyl-7-cyclopentylamino-1H-indol-2-yl)-thiazol-5-yl]méthanol ;
l'ester éthylique d'acide [2-(5-méthyl-7-cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-carboxylique;
l'acide [2-(5-méthyl-7-cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-carboxylique;
le [2-(7-cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]méthanol ;
l'ester méthylique d'acide [2-(7-cyclopentylamino-1H-indol-2-yl)-thiazol-4-yl]-carboxylique;
la 2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-1-morpholin-4-yl-éthanone ;
la 2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-1-(morpholin-4-yl)-éthylaminoéthanone ;
la 2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-1-(morpholin-4-yl)-propylaminoéthanone ;
la 2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-1-méthylaminoéthanone ;
la 2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-1-diméthylaminoéthanone ;
la 2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-1-(4-(méthyl)pipérazin-1-yl)-éthanone ;
la 2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-1-(3-diméthylaminopyrrolidin-1-yl)-éthanone ;
la 2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-1-(pipéridin-4-yl)-éthanone ;
la 2-[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-1-(4-(méthyl)pipérazin-1-yl)-éthanone ;
la 2-[(R)-2-(5-fluoro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-1-(morpholin-4-yl)-éthylaminoéthanone ;
la 2-[(R)-2-(5-méthoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-1-(méthylamino)4-yl-éthanone ;
la 2-[(R)-2-(5-méthoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-1-(morpholin-4-yl)-éthanone ;
la 2-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-1-méthylaminoéthanone ;
la 2-[(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-1-(morpholin-4-yl)-éthanone ;
la 2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-1-(morpholin-4-yl)-éthylaminoéthanone ;
la 2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-1-(4-(méthyl)pipérazin-1-yl)-éthanone ;
la {5-méthanesulfonylméthyl-2-[(R)-4-(2-morpholin-4-yléthyl)-4,5-dihydrothiazo1-2-yl]-1H-indol-7-yl}cyclopentylamine ;
la 1-(4-{2-[(R)-2-(7-cyclopentylamino-5-méthanesulfonylméthyl-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthyl}-pipérazin-1-yl)-éthanone ;
la [2-((R)-4-pyrrolidin-1-ylméthyl-4,5-dihydrothiazol-2-yl)-1H-indol-7-yl]-cyclopentylamine ;
la {5-chloro-2-[(R)-4-(2-diméthylaminoéthyl)-4,5-dihydrothiazol-2-yl]-1H-indol-7-yl}-cyclopentylamine ;
la {5-chloro-2-[(R)-4-(2-pipérazin-1-yléthyl)-4,5-dihydrothiazol-2-yl]-1H-indol-7-yl}-cyclopentylamine ;
la (5-chloro-2-{(R)-4-[2-(4-éthanesulfonylpipérazin-1-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la 1-(4-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthyl}-pipérazin-1-yl)-2-hydroxyéthanone ;
la {5-chloro-2-[(R)-4-(2-pyrazol-1-yléthyl)-4,5-dihydrothiazol-2-yl]-1H-indol-7-yl}-cyclopentylamine ;
l'acide (S)-1-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthyl}-pyrrolidine-2-carboxylique ;
la {5-chloro-2-[(R)-4-(2-méthanesulfonyléthyl)-4,5-dihydrothiazol-2-yl]-1H-indol-7-yl}-cyclopentylamine ;
l'ester éthylique d'acide 3-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthyl}-5-méthyl-3H-imidazole-4-carboxylique ;
l'acide 3-{2-[(R)-2-(5-chloro-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthyl}-5-méthyl-3H-imidazole-4-carboxylique ;
la {2-[(R)-4-(2-méthoxyéthyl)-4,5-dihydrothiazol-2-yl]-1H-indol-7-yl}-cyclopentylamine ;
la [2-((R)-4-aminométhyl-4,5-dihydrothiazol-2-yl]-1H-indol-7-yl]-cyclopentylamine ;
la {2-[(R)-4-((R)-3-aminopyrrolidin-1-yléthyl)-4,5-dihydrothiazol-2-yl]-5-chloro-1H-indol-7-yl]-cyclopentylamine ;
la 4-[(R)-2-(7-cyclopentylamino-5-éthoxy-1H-indol-2-yl)-4,5-dihydrothiazol-4-yléthyl]-pipérazin-2-one ;
la {2-[(R)-4-((S)-3-aminopyrrolidin-1-yléthyl)-4,5-dihydrothiazol-2-yl]-5-chloro-1H-indol-7-yl}cyclopentylamine ;
la (5-chloro-2-{(S)-4-[2-(3-diméthylaminophényl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la 1-(4-{2-[(S)-2-(7-cyclopentylamino-5-chloro-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthyl}-pipérazin-1-yl)-éthanone ;
la 1-(4-{2-[(S)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthyl}pipérazin-1-yl)-éthanone ;
la (5-méthoxy-2-{(R)-4-[2-pyrrolidin-1-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-méthanesulfonylméthyl-2-{(S)-4-[2-oxopipérazin-4-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la 1-(4-{2-[(R)-2-(7-cyclopentylamino-5-chloro-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthyl}-pipérazin-1-yl)-éthanone ;
la (5-chloro-2-{(R)-4-[4-méthylpipérazin-1-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-chloro-2-{(R)-4-[4-(hydroxy)pipéridin-1-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-chloro-2-{(R)-4-[2-oxopipérazin-4-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-chloro-2-{(R)-4-[(pipéridin-1-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-chloro-2-{(R)-4-[1,1-dioxothiomorpholin-4-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-chloro-2-{(R)-4-[2-oxopyrrolidin-1-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-fluoro-2-{(R)-4-(2-aminoéthyl)-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la 1-(4-{2-[(R)-2-(5-fluoro-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthyl}-pipérazin-1-yl)-2-hydroxyéthanone ;
la (5-fluoro-2-{(R)-4-[(morpholin-4-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-fluoro-2-{(R)-4-(2-diméthylaminoéthyl)-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-fluoro-2-{(R)-4-[(pyrrolidin-1-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-fluoro-2-{(R)-4-[(1,1-dioxothiomorpholin-4-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-fluoro-2-{(R)-4-[(2-oxopyrrolidin-1-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la 1-(4-{2-[(5-fluoro-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthyl}-pipérazin-1-yl)-2-hydroxyéthanone ;
la (5-fluoro-2-{(R)-4-[méthanesulfonyléthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (2-{(R)-4-[2-diméthylaminoéthyl)-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (2-{(R)-4-[(pipéridin-1 -yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la 1-(4-{2-[(R)-2-(5-méthoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthyl}-pipérazin-1-yl)-2-hydroxyéthanone;
la 1-(4-{2-[(R)-2-(7-cyclopentylamino)-5-chloro-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-propyl}-pipérazin-1-yl)-éthanone ;
la 2-{(R)-4-[(morpholin-4-yl)-méthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-chloro-2-{(R)-4-[(morpholin-4-yl)-propyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (2-{(R)-4-(2-diméthylaminométhyl)-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-chloro-2-{(S)-4-[(morpholin-4-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la 1-(4-{2-[(S)-2-(5-phénoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthyl}-pipérazin-1-yl)-2-hydroxyéthanone;
la (5-phénoxy-2-{(S)-4-[(pipérazin-1-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
le t-butyl-(4-{2-[(S)-2-(5-phénoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthyl}-pipérazin-1-carboxylate ;
la (5-phénoxy-2-{(S)-4-[2-(3-fluorométhyl-5,6-dihydro-8H-[1,2,4]triazolo[4,3-a]pyrazin-7-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine;
la (5-phénoxy-2-{(S)-4-[2-oxopipérazin-4-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (4-{2-[(S)-2-(5-phénoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthyl}-pipérazin-1-yl)-oxoran-2-yl-méthanone ;
la (5-phénoxy-2-{(S)-4-[(pyridin-2-yl)pipérazine-éthyl]-4,5-dihydrothiazol-2-yl}-1 H-indol-7-yl)-cyclopentylamine ;
la (5-phénoxy-2-{(S)-4-[(2-fluorophényl)pipérazine-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-chloro-2-{(S)-4-[2-oxopipérazin-4-yl)-éthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-phénoxy-2-{(S)-4-[(3S)-3-(amino)pyrrolidin-1-yléthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la 1-(4-{2-[(S)-2-(5-phénoxy-7-cyclopentylamino)-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthyl}-pipérazin-1-yl)-éthanone ;
le (5-chloro-[(S)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl])-pyrrolidin-3-yl-acétamide ;
la (5-phénoxy-2-{(S)-4-[4-(benzyl)pipérazin-1-yléthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-phénoxy-2-{(R)-4-[pyrrolidin-1-yléthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-phénoxy-2-{(S)-4-[pyrrolidin-1-yléthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-cyclopentylamine ;
la (5-méthyl-2-{(S)-4-[2-oxopipérazin-4-yléthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-4,4-difluorocyclohexylamine ;
la (5-méthyl-2-{(S)-4-[morpholin-4-yléthyl]-4,5-dihydrothiazol-2-yl}-1H-indol-7-yl)-4,4-difluorocyclohexylamine ;
la 1-(4-{2-[(R)-2-(5-méthoxy-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-éthyl}-pipérazin-1-yl)-2-hydroxyéthanone ;
le [(R)-2-(5-aminométhyl-7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-yl]-méthanol ;
le [7-cyclopentylamino-2-((R)-4-hydroxyméthyl-4,5-dihydrothiazol-2-yl)-1H-indol-5-ylméthyl]-amide d'acide furan-2-carboxylique ;
l'ester méthylique d'acide [(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-ylméthoxy]-acétique ;
l'acide [(R)-2-(7-cyclopentylamino-1H-indol-2-yl)-4,5-dihydrothiazol-4-ylméthoxy]-acétique ;
la {2-[(R)-4-(3-cyclopentyl-[1,2,4]oxadiazol-5-ylméthyl)-4,5-dihydrothiazol-2-yl]-1H-indol-7-yl}-amine ; et
la {2-[(R)-4-(3-pipéridin-1-yl-[1,2,4]oxadiazol-5-ylméthyl)-4,5-dihydrothiazol-2-yl]-1H-indol-7-yl}-amine.
REFERENCES CITED IN THE DESCRIPTION
Patent documents cited in the description
Non-patent literature cited in the description