Tetrahydronaphthyridinyl-carboxamides having anti-convulsant...

C - Chemistry – Metallurgy – 07 – D

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C07D 471/04 (2006.01) A61K 31/44 (2006.01) C07D 221/00 (2006.01) C07D 471/10 (2006.01)

Patent

CA 2334900

Compounds of formula (I) and pharmaceutically acceptable salts and solvates: where R1 is hydrogen, C1-6alkyl (optionally substituted by hydroxy or C1- 4alkoxy), phenyl-C1-4alkyl-, C1-6alkenyl, C1-6alkynyl; R2 is hydrogen or up to three substituents selected from halogen, NO2, CN, N3, CF3O-, CF3S-, CF3SO2-, CF3CO-, C1-6alkyl, C1-6alkenyl, C1-6alkynyl, C1-6perfluoroalkyl, C3- 6cycloalkyl, C3-6cycloalkyl-C1-4alkyl-, C1-6alkylO-, C1-6alkylCO-, C3- 6cycloalkylO-, C3-6cycloalkylCO-, C3-6cycloalkyl-C1-4alkylO-, C3-6cycloalkyl- C1-4alkylCO-, phenyl, phenoxy, benzyloxy, benzoyl, phenyl-C1-4alkyl-, C1- 6alkylS-, C1-6alkylSO2-, (C1-4alkyl)2NSO2-, (C1-4alkyl)NHSO2-, (C1-4alkyl)2NCO- , (C1-4alkyl)NHCO- or CONH2; or -NR5R6 where R5 is hydrogen or C1-4alkyl, and R6 is hydrogen, C1-4alkyl, formyl, -CO2C1-4alkyl or -COC1-4alkyl; or two R2 groups together form a carbocyclic ring that is saturated or unsaturated, optionally interrupted by O or NH; R3 groups and R4 groups are each independently hydrogen or C1-6alkyl and/or the two R3 groups and/or the two R4 groups together form a C3-6spiroalkyl group, provided that at least one R3 or R4 group is not hydrogen; and X is selected from hydrogen, halogen, cyano, alkyl and alkoxy, are useful in the treatment and prophylaxis of epilepsy, migraine, and other disorders.

La présente invention concerne des composés représentés par la formule générale (I) ainsi que certains de leurs sels et solvates pharmaceutiquement acceptés. Ces composés conviennent au traitement et à la prophylaxie de l'épilepsie, de la migraine et d'autres troubles. En l'occurrence, R?1¿ est hydrogène, C¿1-6?alkyle (éventuellement substitué par hydroxy ou C¿1-4?alcoxy), phényle-C¿1-4?alkyle-, C¿1-6?alcényle, C¿1-6?alkynyle; R?2¿ est hydrogène ou un maximum de trois substituants choisis parmi halogène, NO¿2?, CN, N¿3?, CF¿3?O-, CF¿3?S-, CF¿3?SO¿2?-, CF¿3?CO-, C¿1-6?alkyle, C¿1-6?alcényle, C¿1-6?alkynyle, C¿1-6?perfluoroalkyle, C¿3-6?cycloalkyle, C¿3-6?cycloalkyle-C¿1-4?alkyle-, C¿1-6?alkyleO-, C¿1-6?alkyleCO-, C¿3-6?cycloalkyleO-, C¿3-6?cycloalkyleCO-, C¿3-6?cycloalkyle-C¿1-4?alkyleO-, C¿3-6?cycloalkyle-C¿1-4?alkyleCO-, phényle, phénoxy, benzyloxy, benzoyl, phényle-C¿1-4?alkyle-, C¿1-6?alkyleS-, C¿1-6?alkyleSO¿2?-, (C¿1-4?alkyle)¿2?NSO¿2?-, (C¿1-4?alkyle)NHSO¿2?-, (C¿1-4?alkyle)¿2?NCO-, (C¿1-4?alkyle)NHCO- ou CONH¿2?; ou -NR?5¿R?6¿ auquel cas R?5¿ est hydrogène ou C¿1-4?alkyle, et R?6¿ est hydrogène, C¿1-4?alkyle, formyle, -CO¿2?C¿1-4?alkyle ou -COC¿1-4?alkyle; ou deux groupes R?2¿ forment ensemble un cycle carbocyclique qui est saturé ou insaturé, éventuellement interrompu par O ou NH; les groupes R?3¿ et R?4¿ sont chacun indépendamment hydrogène ou C¿1-6?alkyle et/ou les deux groupes R?3¿ et/ou les deux groupes R?4¿ forment ensemble un groupe C¿3-6?spiroalkyle, à condition que l'un au moins du groupe R?3¿ ou R?4¿ ne soit pas hydrogène; et X est hydrogène, halogène, cyano, alkyle ou alcoxy.

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