Amide derivatives as glycogen synthase kinase 3-beta inhibitors

C - Chemistry – Metallurgy – 07 – D

Patent

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C07D 213/82 (2006.01) A61K 31/505 (2006.01) A61P 3/10 (2006.01) A61P 25/28 (2006.01) C07D 213/81 (2006.01) C07D 239/42 (2006.01) C07D 401/12 (2006.01) C07D 403/12 (2006.01) C07D 405/12 (2006.01) C07D 407/12 (2006.01) C07D 413/12 (2006.01) C07D 413/14 (2006.01) C07D 417/12 (2006.01)

Patent

CA 2463821

This invention concerns a compound of formula (I' ),a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein ring A represents a 6-membered heterocycle; R1 is hydrogen; aryl; formyl; C1-6alkylcarbonyl; optionally substituted C1-6alkyl; C1-6alkyloxycarbonyl; optionally substituted C1- 6alkyloxyC1-6alkylcarbonyl; X is a direct bond or a linker atom or group; Z is O or S; R2 is hydrogen, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, a carbocycle or a heterocycle, each of said groups may optionally be substituted; R3 is hydrogen; hydroxy; halo; optionally substituted C1-6alkyl or C2-6alkenyl or C2- 6alkynyl; C1-6alkyloxy; C1-6alkylthio; C1-6alkyloxycarbonyl; C1- 6alkylcarbonyloxy; carboxyl; cyano; nitro; amino; mono- or di(C1-6alkyl)amino; polyhaloC1-6alkyl; polyhaloC1-6alkyloxy; polyhaloC1-6alkylthio; R21; R21-C1- 6alkyl; R21-O-; R21-S-; R21-C(=O)-; R21-S(=O)p-; R7-S(=O)p-; R7-S(=O)p-NH-; R21-S(=O)p-NH-; R7-C(=O)-; -NHC(=O)H;-C(=O)NHNH2; R7-C(=O)-NH-; R21-C(=O)-NH-; -C(=NH)R7; -C(=NH)R21 ; R4a or R4b each independently represent hydrogen, R8, - Y1-NR9-Y2-NR10R11, -Y1-NR9-Y1-R8, -Y1-NR9R10; provided that -X-R2 and/or R3 is other than hydrogen; their use, pharmaceutical compositions comprising them and processes for their preparation.

L'invention concerne un composé de formule (I), ainsi qu'un N-oxyde, un sel d'addition de qualité pharmaceutique, une amine quaternaire et une forme isomère stéréochimique de ce composé, dans laquelle le cycle A représente un hétérocycle à 6 éléments; R?1¿ représente hydrogène; aryle; formyle; alkylcarbonyle C¿1-6?; alkyle C¿1-6? facultativement substitué; alkyloxycarbonyle C¿1-6?; alkyloxy C¿1-6 ?alkylcarbonyle C¿1-6? facultativement substitué; X est une liaison directe ou un atome ou un groupe de liaison; Z représente O ou S; R?2¿ représente hydrogène, alkyle C¿1-10?, alcényle C¿2-10?, alcynyle C¿2-10?, un carbocycle ou un hétérocycle, chacun desdits groupes pouvant être facultativement substitué; R?3¿ représente hydrogène; hydroxy; halo; alkyle C¿1-6? ou alcényle C¿2-6? ou alcynyle C¿2-6? facultativement substitué; alkyloxy C¿1-6?; alkylthio C¿1-6?; alkyloxycarbonyle C¿1-6?; alkylcarbonyloxy C¿1-6?; carboxyle; cyano; nitro; amino; mono- ou di(C¿1-6?alkyl)amino; polyhalo alkyle C¿1-6?; polyhalo alcoxy C¿1-6?; polyhalo alkylthio C¿1-6?; R?21¿; R?21¿-alkyle C¿1-6?; R?21¿-O-; R?21¿-S-; R?21¿-C(=O)-; R?21¿-S(=O)¿p?-; R?7¿-S(=O)¿p?-; R?7¿-S(=O)¿p?-NH-; R?21¿-S(=O)¿p?-NH-; R?7¿-C(=O)-; -NHC(=O)H; -C(=O)NHNH¿2?; R?7¿-C(=O)-NH-; R?21¿-C(=O)-NH-; -C(=NH)R?7¿; -C(=NH)R?21¿; R?4a¿ ou R?4b¿ représente chacun indépendamment hydrogène, R?8¿, -Y¿1?-NR?9¿-Y¿2?-NR?10¿R?11¿, -Y¿1?-NR?9¿-Y¿1?-R?8¿, -Y¿1?-NR?9¿R?10¿; à condition que -X-R?2¿ et/ou R?3¿ représente autre chose qu'hydrogène. L'invention concerne également l'utilisation dudit composé, ou de ses sels, amines ou formes isomères, ainsi que des compositions pharmaceutiques contenant ledit composé, ou ses sels, amines ou formes isomères, et des procédés de préparation associés.

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