NAPHTHYL BENZOFURAN DERIVATIVES AS INHIBITORS OF PLASMINOGENACTIVATOR INHIBITOR-1 (PAI-1)

摘要

This invention provides compounds which act as inhibitors of plasminogen activator inhibitor-1 (PAI-1) of the formula (1), wherein: R, R1, R2, and R3 are H, alkyl, cycloalkyl, -CH2-(cycloalkyl), alkanoyl, halo, hydroxy, aryl, substituted aryl, heteroaryl, substituted heteroaryl, perfluoroalkyl, alkoxy , amino, -NH(alkyl), -N(alkyl)2, or perfluoroalkoxy; R4 is H, alkyl, perflouroalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkenyl, alkenyl-aryl, aryl, -CH2R5, -CH(OH)R5, -C(O)R5, -CH(SH)R5, or - G(S)R5; R5 is H, alkyl, perflouroalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, alkenyl, alkenyl-aryl; R6 is H, alkyl, cycloalkyl, - CH2-cycloalkyl, alkylaryl, aryl, substituted aryl, heteroaryl, or substitute d heteroaryl; n is an integer of 0-6; A is COOH, or an acid mimic; or a pharmaceutically acceptable salt or ester form thereof, as well as pharmaceutical compositions and methods using these compounds to treat or prevent conditions resulting from fibrinolytic disorders such as deep vein thrombosis and coronary heart disease, and pulmonary fibrosis, and processes for the preparation of such compounds.