Aryloxy-acetic acid compounds useful as inhibitors of plasminogen activator inhibitor-1 (PAI-1)

摘要

This invention provides methods of inhibiting plasminogen activator inhibitor-1 (PAI-1) in a mammal, utilizing compounds of the formula: wherein: A is C or N; B is O, S, N, or CH-CH; X is CO, CH(OH), CH₂, or -CH-S-2-benzothiazole; Y is H, alkyl, or halo; Z is O, S, or N; R is H, nitro, alkyl, alkoxy, halo, or CF₃; R¹ is alkyl, aryl, aralkyl, halo, Het-alkyl, or optionally substituted aryl; Het is G is O, S, or N; R² is H, halo, alkyl, or -OR⁵; R³ and R⁴ are H, halo, alkyl, aryl, nitro, amino, alkylsulfoamide, arylsulfoamide, cycloalkyl, heterocycle, or optionally substituted aryl; R⁵ is H, alkyl, -CH(R⁷)R⁸, -C(CH₂)_nCO₂R⁹, -C(CH₃)₂CO₂R⁹, CH(R⁷)(CH₂)_nCO₂R⁹, or -CH(R⁷)C₆H₄CO₂R⁹; R⁶ is alkylene; R⁷ is H, alkyl, aryl, aralkyl, cycloalkyl, phthalic acid, or Q-alkyl; Q is R⁸ is -CO₂R¹¹, -CONHR¹¹, tetrazole, or -PO₃R¹¹; R⁹ is H, alkyl, aryl, or aralkyl; W is O, N, or S; R¹¹ is H, alkyl, aryl, or aralkyl; n=1-6; or a pharmaceutically acceptable salt or ester form thereof.