EP 2185511 A2 20100519 - 1-OXO-ISOINDOLINE-4-CARBOXAMIDE AND 1-OXO-1,2,3,4-TETRAHYDROISOQUINOLINE-5-CARBOXAMIDE DERIVATIVES, PREPARATION AND THERAPEUTIC USE THEREOF
Title (en)
1-OXO-ISOINDOLINE-4-CARBOXAMIDE AND 1-OXO-1,2,3,4-TETRAHYDROISOQUINOLINE-5-CARBOXAMIDE DERIVATIVES, PREPARATION AND THERAPEUTIC USE THEREOF
Title (de)
1-OXO-ISOINDOLIN-4-CARBOXAMID- UND 1-OXO-1,2,3,4-TETRAHYDROISOCHINOLIN-5-CARBOXAMID-DERIVATE SOWIE DEREN HERSTELLUNG UND THERAPEUTISCHE VERWENDUNG
Title (fr)
DÉRIVÉS DE 1-OXO-ISOINDOLINE-4-CARBOXAMIDES ET DE 1-OXO-1,2,3,4-TETRAHYDROISOQUINOLEINE-5-CARBOXAMIDES, LEUR PRÉPARATION ET LEUR APPLICATION EN THÉRAPEUTIQUE
Publication
Application
Priority
- FR 2008001110 W 20080725
- FR 0705499 A 20070727
Abstract (en)
[origin: FR2919285A1] 1-Oxo-isoindoline-4-carboxamide and 1-oxo-1,2,3,4-tetrahydroisoquinoline-5-carboxamide compounds (I) and their base or acid addition salts, hydrates or solvates are new. 1-Oxo-isoindoline-4-carboxamide and 1-oxo-1,2,3,4-tetrahydroisoquinoline-5-carboxamide compounds of formula (I) and their base or acid addition salts, hydrates or solvates are new. R 1>H, 1-10C alkyl, 3-7C cycloalkyl, (CH 2) n-(1-6C)alkenyl, (CH 2) n-(1-6C)alkynyl, 1-6C alkyl-Z-(1-6C alkyl), aryl or aralkyl (all optionally substituted by halo, 1-6C alkyl, 3-7C cycloalkyl, halo(1-6C)alkyl, 1-6C alkoxy, halo(1-6C)alkoxy, NR 7>R 8>, nitro, cyano, OR, COOR, CONR 7>R 8>or S(O) mNR 7>R 8>), COOR or S(O) mR; Z : heteroatom comprising O, N or S(O) m; R 2>halo(1-6C)alkyl, halo(1-6C)alkoxy, OH, 1-6C alkoxy, NO 2, CN, NH 2, NR 7>R 8>, COOR, CONR 7>R 8>, OCO(1-6C)alkyl, S(O) mNR 7>R 8>or aryl (all optionally substituted by one or more halo, 1-6C alkyl, 3-7C cycloalkyl, halo(1-6C)alkyl, (1-6C)alkoxy, halo(1-6C)alkoxy, NR 7>R 8>, NO 2, CN, OR, COOR, CONR 7>R 8>or S(O) mNR 7>R 8>), H (preferred), halo, 1-6C alkyl, 3-7C cycloalkyl, (1-6C)alkenyl, (1-6C)alkynyl or 1-6C alkyl-Z-(1-6C alkyl); R 3>CF 3; either R 4>, R 5>H; or CR 4>R 5>ring containing 3-6 carbon atoms (optionally saturated and optionally containing 0 or 1 heteroatom comprising O, N or S); R 6>H (preferred), halo, 1-6C alkyl, 3-7C cycloalkyl, 3-7C cycloalkyl-1-6C alkyl, NO 2, NH 2, NR 7>R 8>, COOR, NR 7>(SO 2)R 8>, CONR 7>R 8>or aryl; either R 7>, R 8>, R : H, 1-6C alkyl, 3-7C cycloalkyl, 3-7C cycloalkyl-1-6C alkyl, aryl, aryl(1-6C)alkylene or COR; or R 7>R 8>ring containing 5-7 carbon atoms (optionally saturated and substituted by heteroatom of O, N or S(O) m); X : 1-2C alkylene (optionally substituted by one or more 1-6C alkyl group); m : 0-2; and n : 1-6. Where the carbon carrying the benzyl substituted by R2 is absolute configuration S and the carbon carrying the hydroxyl is absolute configuration R. Independent claims are included for: (1) substituted 1-oxo-2,3-dihydro-1H-isoindole-4-carboxylic acid compounds of formula (IIIa); and (2) substituted 1-oxo-1,2,3,4-tetrahydro-isoquinoline-5-carboxylic acid of formula (IIIb) and (IIIc). [Image] [Image] ACTIVITY : Neuroprotective; Nootropic; Antiparkinsonian; Cerebroprotective; Vasotropic; Cardiovascular-gen.; Anticonvulsant; Antimigraine; Antidepressant; Tranquilizer; Antiarteriosclerotic; Cytostatic. MECHANISM OF ACTION : Beta-secretase inhibitor. The ability of (I) to inhibit beta-secretase was tested using fluorescence resonance energy transfer assay. The result showed that N-[(1S,2R)-1-(3,5-difluorobenzyl)-2-hydroxy-3-({1-[3-(trifluoromethyl)phenyl]cyclopropyl}amino)propyl]-7-[methyl(methylsulfonyl)amino]-1-oxo-2-(1-propylbutyl)-1,2,3,4-tetrahydroisoquinoline-5-carboxamide hydrochloride exhibited an IC 5 0value of 0.048 mu M.
IPC 8 full level
A61K 31/4035 (2006.01); A61K 31/472 (2006.01); A61P 9/00 (2006.01); A61P 25/00 (2006.01); A61P 35/00 (2006.01); C07D 209/46 (2006.01); C07D 217/24 (2006.01); C07D 413/12 (2006.01)
CPC (source: EP US)
A61P 9/00 (2017.12 - EP); A61P 9/10 (2017.12 - EP); A61P 25/00 (2017.12 - EP); A61P 25/02 (2017.12 - EP); A61P 25/06 (2017.12 - EP); A61P 25/14 (2017.12 - EP); A61P 25/16 (2017.12 - EP); A61P 25/22 (2017.12 - EP); A61P 25/24 (2017.12 - EP); A61P 25/28 (2017.12 - EP); A61P 35/00 (2017.12 - EP); A61P 43/00 (2017.12 - EP); C07D 209/46 (2013.01 - EP US); C07D 217/24 (2013.01 - EP US); C07D 413/12 (2013.01 - EP US)
Citation (search report)
See references of WO 2009044019A2
Designated contracting state (EPC)
AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR
Designated extension state (EPC)
AL BA MK RS
DOCDB simple family (publication)
FR 2919285 A1 20090130; FR 2919285 B1 20120831; AU 2008306763 A1 20090409; AU 2008306763 B2 20130829; BR PI0813624 A2 20190924; CA 2694322 A1 20090409; CN 101790514 A 20100728; CN 101790514 B 20121219; CO 6290678 A2 20110620; EA 201070197 A1 20100830; EP 2185511 A2 20100519; HK 1143163 A1 20101224; JP 2010534641 A 20101111; JP 5412428 B2 20140212; KR 20100051830 A 20100518; MA 31635 B1 20100802; MX 2010001079 A 20100324; MY 150436 A 20140130; NZ 582873 A 20120727; SG 183082 A1 20120830; US 2010197725 A1 20100805; US 8372864 B2 20130212; WO 2009044019 A2 20090409; WO 2009044019 A3 20090618; WO 2009044019 A9 20101014; ZA 201000582 B 20110428
DOCDB simple family (application)
FR 0705499 A 20070727; AU 2008306763 A 20080725; BR PI0813624 A 20080725; CA 2694322 A 20080725; CN 200880104529 A 20080725; CO 10007698 A 20100126; EA 201070197 A 20080725; EP 08835551 A 20080725; FR 2008001110 W 20080725; HK 10109764 A 20101015; JP 2010517453 A 20080725; KR 20107004339 A 20080725; MA 32652 A 20100224; MX 2010001079 A 20080725; MY PI20100428 A 20080725; NZ 58287308 A 20080725; SG 2012055539 A 20080725; US 69359710 A 20100126; ZA 201000582 A 20100126