ANTITHROMBOTIC N-AMIDINOPIPERIDINE AND BENZAMIDINE DERIVATIVES

摘要

Compounds of formula (I), pharmaceutically acceptable salts thereof, and pharmaceutically acceptable solvates of either entity, wherein A is optionally monounsaturated C4-C5 alkylene optionally substituted with C1-C4 alkyl; B is C1-C3 alkylene optionally substituted with C1-C4 alkyl; R1 is N-amidino-4-piperidyl or 4-amidinophenyl; R2 is C4-C12 alkyl; (C3-C8 cycloalkyl)C1-C4 alkylene; optionally methylene-bridged C5-C8 cycloalkyl optionally substituted with one to three C1-C4 alkyl groups or with hydroxy; C5-C8 alkenyl; C5-C8 cycloalkenyl optionally substituted with C1-C4 alkyl; piperidyl N-substituted with C1-C4 alkyl; tetrahydrothiopyranyl or tetrahydropyranyl; and R3 is H or C1-C4 alkyl optionally substituted with C1-C4 alkoxy or with hydroxy; or R2 and R3, together with the nitrogen atom to which they are attached, form a piperidine ring which is optionally substituted with C1-C4 alkyl or is optionally benzo-fused; are potent and selective thrombin inhibitors useful in the treatment of, inter alia, deep vein thrombosis; reocclusion following thrombolytic therapy; chronic arterial obstruction; peripheral vascular disease; acute myocardial infarction; unstable angina; atrial fibrillation; thrombotic stroke; transient ischaemic attacks; restenosis and occlusion following angioplasty; or neurodegenerative disorders.