Azetidinone derivatives for the treatment of atherosclerosis

Details Azetidinone derivatives for the treatment of atherosclerosis Azetidinone derivatives for the treatment of atherosclerosis

C - Chemistry, Metallurgy

07

D

C07D 205/09 (2006.01) A61K 31/395 (2006.01) C07D 405/12 (2006.01)

Patent

CA 2252696

Selected compounds of formula (I) in which: R1 is hydrogen or a corresponding pharmaceutically acceptable ester or a pharmaceutically acceptable salt thereof; R2 and R3 which may be the same or different is each selected from hydrogen or optionally substituted C(1-6)alkyl; X is a group X'(CH2)m in which X' is CO, CONR4, COO, CONR4CO, CONHO or CH2O in which R4 is hydrogen or C(1- 6)alkyl and m is 0 or an integer from 1 to 12; or a C(1-12)alkylene chain optionally interrupted by X'; and Y is an optionally substituted aryl group; having the absolute configuration (4R,SS); are inhibitors of the enzyme Lp- PLA2 and thereof of use in treating atherosclerosis.

On décrit des composés choisis de la formule (I) dans laquelle R?1¿ représente hydrogène, ou un ester correspondant, ou un sel de celui-ci, acceptables sur le plan pharmacologique, R?2¿ et R?3¿ qui peuvent être semblables ou différents sont choisis chacun parmi hydrogène ou alkyle C¿(1-6)? éventuellement substitué, X représente soit un groupe X'(CH¿2?)¿m?, dans lequel X' représente CO, CONR?4¿, COO, CONR?4¿CO, CONHO ou CH¿2?O, où R?4¿ représente hydrogène ou alkyle C¿(1-6)? et m vaut 0 ou est un nombre entier compris entre 1 et 12, soit une chaîne alkylène C¿(1-12)? éventuellement interrompue par X', Y représentant un groupe aryle éventuellement substitué. Ces composés présentent la configuration absolue (4RSS), constituent des inhibiteurs de l'enzyme Lp-PLA¿2? et sont, par conséquent, utiles pour traiter l'athérosclérose.

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