Substituted naphthyl benzofuran derivatives as inhibitors of plasminogen activator inhibitor-1 (PAI-1)

US6599925B2 · kind B2 · utility

Assignee

• Wyeth, LLC · US

Inventors

• Hassan Mahmoud Elokdah · North Wales, US
• Geraldine Ruth McFarlane · Monmouth Junction, US
• Scott Mayer · Lawrence, US
• David LeRoy Crandall · Doylestown, US

Key dates

• Filing date: Jun 18, 2002
• Grant date: Jul 29, 2003
• Expiry date: Jun 18, 2022

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D307/80
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

This invention provides compounds which act as inhibitors of plasminogen activator inhibitor-1 (PAI-1) of the formula: 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 —C(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 substituted 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.