Patent FR-2932478-A1 (FR)
Title: New amide compounds useful for treatment or prevention of cancer, preferably cancer resistant to chemotherapy
Inventor: CARNIATO DENIS
IPC: C07D407/12
Filed: 2009-04-17
Abstract: Amide compounds (I) and their salts, isomers or mixtures of isomers in all proportions, including mixture of enantiomer and racemic mixture are new. Amide compounds of formula (R1-N(R2)-C(=O)-C(R3)(R4)-N(R5)-C(=O)-R6) (I) and their salts, isomers or mixtures of isomers in all proportions, including mixture of enantiomer and racemic mixture are new. Either R1 : H, (1-6C)alkyl, (3-10C)cycloalkyl, (3-10C)cycloalkenyl, aryl, heteroaryl, aryl-(1-6C)alkyl or heteroaryl-(1-6C)alkyl (all optionally substituted by one or more groups comprising halo, (1-6C)alkoxy, -NH 2, -COOH, -CN, -OH, -NR7R8, -O-(1-6C)alkyl-NR7R8, benzyloxy, aryloxy,-C(O)O-(1-6C)alkyl, -NH-C(O)O-(1-6C)alkyl, -C(O)NH 2, -C(O)NR9R10, -S-(1-6C)alkyl, -S(O)-(1-6C)alkyl, -SO 2-(1-6C)alkyl, -SO 2NH 2, -O 2NR11R12, -NR13SO 2R14 or (1-6C)alkyl (optionally substituted by one or more halo)); and R2 : H or (1-6C)alkyl, preferably (1-4C)alkyl; or N+R1R2 : heteroaryl (optionally substituted by one or more groups comprising halo, -CN, -NH 2, -NR40R41, -NO 2, -OH, (1-6C)alkoxy, aryloxy, benzyloxy, -O(1-6C)alkyl-NR42R43, -C(O)O-(1-6C)alkyl, -NHC(O)O-(1-6C)alkyl-C(O)NH 2, -C(O)NR44R45, -SO 2NH 2, -SO 2NR46R47 or NR48SO 2R49) or heterocyclic ring of 3-7 members (optionally substituted by one or more groups comprising halo, (3-10C)cycloalkyl, (3-10C)cycloalkenyl, aryl, heteroaryl, aryl-(1-6C)alkyl, heteroaryl-(1-6C)alkyl, heterocycloalkyl-(1-6C)alkyl, -OH, -NH 2, -C(O)OH, -C(O)NH 2, -C(S)NH 2, -OR50, -OC(O)R51, -C(O)R52, -C(O)OR53, -NHC(O)R54, -NHC(O)OR55, -SO 2R56, -(1-6C)alkyl, -C(O)OR57, -NR58R59, -C(O)NR60R61, -C(O)N(R62)(aryl), C(O)N(R63)(heteroaryl), -C(O)NHNR64R65, -C(S)NR66R67, C(S)N(R68)(aryl), -C(S)N(R69)(heteroaryl), -C(S)NHNR70R71, -OC(O)-NR72R73, -(1-6C)alkyl-C(O)-NR74R75, -(1-6C)alkyl-NR103-C(O)-OR104, -(1-6C)alkyl-NR76R77, -C(NOR78)-aryl or (1-6C)alkyl (optionally substituted by one or more halo)), where aryl and heteroaryl radical are optionally substituted by one or more groups comprising halo, -CN, -OH, (1-6C)alkyl, (1-6C)alkoxy, -NR79R80, -(1-6C)alkyl-NR81R82 or -O-(1-6C)alkyl-NR83R84; either R3 : H or (1-6C)alkyl, preferably (1-4C)alkyl, or -(1-6C)alkyl-NR15R16; and R4 : H or (1-6C)alkyl, (3-10C)cycloalkyl, aryl (preferably phenyl) or heteroaryl (preferably thiophenyl) (all optionally substituted by one or more groups comprising halo, -C(CF 3) 2OH, -CN, -NH 2, -OPO 3H 2, -NR17R18, -NO 2, -COOH, -OH, -O(1-6C)alkyl-OPO 3H 2, -O-(1-6C)alkyl-O-(1-6C)alkyl, -O(1-6C)alkyl-NR19R20, NR81-(1-6C)alkyl, -NR85R86, benzyloxy, -C(O)O-(1-6C)alkyl, -NHC(O)O-(1-6C)alkyl, -C(O)NH 2, -C(O)NR21R22, -S-(1-6C)alkyl, -S(O)-(1-6C)alkyl, -SO 2-(1-6C)alkyl, -SO 2NH 2, -SO 2NR23R24, -NR25SO 2R26, 3-7-membered heterocycloalkyl ring, aryloxy, (1-6C)alkyl (optionally substituted by one or more halo) or (1-6C)alkoxy (optionally substituted by one or more F)), where the aryl or heteroaryl is optionally fused to a heterocyclic 5 or 6 membered ring; or C+R3R4 : ring comprising (3-10C)cycloalkyl or 3-7 membered heterocycloalkyl (both optionally substituted by (1-6C)alkyl, -C(O)-(1-6C)alkyl or -C(O)O-(1-6C)alkyl); R5 : (1-6C)alkyl, (3-10C)cycloalkyl, (3-10C)cycloalkenyl, aryl, heteroaryl, aryl-(1-6C)alkyl, heteroaryl-(1-6C)alkyl, (3-10C)cycloalkyl-(1-6C)alkyl or 3-7 membered heterocycloalkyl-(1-6C)alkyl (all optionally substituted by one or more groups comprising halo, NH 2, -COOH, -CN, -OH, -NO 2, -B(OH) 2, (1-6C)alkoxy, -O-(1-6C)alkyl-NR27R28, -O-(1-6C)alkyl-O-(1-6C)alkyl, aryloxy, -C(O)O-(1-6C)alkyl, (2-6C)alkynyl, -NR29R30, -NHC(O)O-(1-6C)alkyl, -C(O)NH 2, -C(O)NR31R32, -S-(1-6C)alkyl, -S(O)-(1-6C)alkyl, -SO 2-(1-6C)alkyl, -SO 2NH 2, -SO 2NR33R34, NR35SO 2R36-, aryl, heteroaryl, (1-6C)alkyl-heteroaryl, 3-7 membered heterocycloalkyl, (3-7 membered heterocycloalkyl)-(1-6C)alkoxy or (1-6C)alkyl (optionally substituted by one or more halo)), where the aryl or heteroaryl, when present, is optionally fused to form a 5 or 6 membered heterocyclic ring; R6 : -CHR37-Hal or -C?=CR38; Hal : halo; either R19, R20, R85, R86 : (1-6C)alkyl; or N+R19R20, N+R85R86 : 3-7 membered heterocyclic ring (optionally substituted by one or more groups comprising halo, (3-10C)cycloalkyl, aryl, heteroaryl, aryl-(1-6C) alkyl, heteroaryl-(1-6C)alkyl, -C(O)OR87, -SO 2R88, -OH, (1-6C)alkoxy, -OC(O)-(1-6C)alkyl, -OC(O)-NR89R90, -NHC(O)O-(1-6C)alkyl, -C(O)NH 2, -C(O)NR91R92, -C(S)NR93R94, -C(O)NHNR95R96, -C(S)NHNR97R98 or (1-6C)alkyl (optionally substituted by one or more halo)), where the aryl or heteroaryl is optionally substituted by one or more groups comprising halo, (1-6C)alkyl, -CN, -OH, NR99R100, (1-6C)alkoxy or -O-(1-6C)alkyl-NR101R102; R7-R13, R15-R18, R21-R25, R27-R35, R37, R40-R48, R58-R84, R89-R103 : H or (1-6C)alkyl, when two groups are carried by a single nitrogen, the two groups form with the nitrogen atom a 3-7 membered heterocycloalkyl; R14, R26, R36, R49 : (1-6C)alkyl; R38 : H or (1-6C)alkyl (preferably methyl) or phenyl; and R50-R57, R87, R88, R104 : (1-6C)alkyl, aryl, heteroaryl, aryl-(1-6C)alkyl, heteroaryl-(1-6C)alkyl, (1-6C)alkyl-aryl or (1-6C)alkyl-heteroaryl. Provided that (I) (where R6 is C?=CR38 and R1 is optionally substituted 1,3-thiazol-2-yl group) is excluded. An independent claim is included for a composition comprising (I) and one or more excipient. ACTIVITY : Cytostatic. MECHANISM OF ACTION : None given.