Himbacine analogues as thrombin receptor antagonists

Details Himbacine analogues as thrombin receptor antagonists Himbacine analogues as thrombin receptor antagonists

C - Chemistry, Metallurgy

07

D

C07D 491/04 (2006.01) A61K 31/34 (2006.01) A61K 31/445 (2006.01) A61P 9/00 (2006.01) A61P 19/02 (2006.01) A61P 29/00 (2006.01) C07D 493/04 (2006.01) C07D 495/04 (2006.01)

Patent

CA 2463628

Heterocyclic-substituted tricyclics of the formula (I) or a pharmaceutically acceptable salts thereof, wherein: n1 and n2 are independently 0-2; Het is an optionally substituted mono-, bi- or tricyclic heteroaromatic group; B is alkyl or optionally substituted alkenyl; R22 is -COR23 or a carboxy, sulfinyl, sulfonyl, sulfonamide or amino acid derivative; R23 is haloalkyl; alkenyl; haloalkenyl; alkynyl; optionally substituted cycloalkyl; cycloalkyl-alkyl; aryl; arylalkyl; heteroaryl; heterocycloalkyl; or -COOH and/or -SO3H substituted alkyl; R1, R2, R3, R9, R10 and R11 are as defined in the specification; are disclosed, as well as pharmaceutical compositions containing them and a method of treating diseases associated with thrombosis, atherosclerosis, restenosis, hypertension, angina pectoris, arrhythmia, heart failure, and cancer by administering said compounds.

L'invention concerne des tricycliques substitués par des hétérocycliques de formule (I) ou des sels pharmaceutiquement acceptables desdits tricycliques. Dans la formule (I), n¿1? et ¿n2? sont 0-2 indépendamment; Het représente un groupe hétéroaromatique mono-, bi- ou tricyclique éventuellement substitué; B représente alkyle ou alkényle éventuellement substitué; R?22¿ représente -COR?23¿ ou un dérivé carboxy, sulfinyle, sulfonyle, sulfonamide ou acide aminé; R?23¿ représente haloalkyle; alkényle; haloalkényle; alkynyle; ou cycloalkyle éventuellement substitué; cycloalkyle-alkyle; aryle; arylalkyle; hétéroaryle; hétérocycloalkyle; ou -COOH et/ou alkyle substitué par -SO¿3?H; R?1¿, R?2¿, R?3¿, R?9¿, R?10¿ et R?11¿ sont tels que définis dans la description. L'invention concerne également des compositions pharmaceutiques contenant ces composés ainsi qu'une méthode de traitement, par administration desdits composés, de maladies associées à : la thrombose, l'athérosclérose, la resténose, l'hypertension, l'angine de poitrine, l'arrhythmie, l'insuffisance cardiaque, et le cancer.

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