Evaluation of a series of thiazole derivatives as inhibitors of plasminogen activator inhibitor-1

Abstract

A series of substituted triazole derivatives is reported by 3-Dimensional Pharmaceuticals to possess inhibitory activity against plasminogen activator inhibitor-1 (PAI-1). PAI-1 is the endogenous inhibitor of tissue plasminogen activator (tPA) and thus an important target in cardiovascular disease. These compounds were prepared by an efficient synthesis and were assayed in vitro in a plasminogen activator-mediated chromogenic assay. The compounds reported showed activity in the 1 – 20 μM range. Three compounds had IC₅₀ values 1 – 2 μM. Thus, this series are interesting leads for the development of more active inhibitors. No mechanistic or in vivo data are presented.

• cancer
• plasminogen activator inhibitor-1 (PAI-1)
• serpin
• thiazoles
• thrombosis
• tissue plasminogen activator (tPA)