Novel Thiazole Derivatives as Inhibitors of Superoxide Production by Human Neutrophils: Synthesis and Structure–Activity Relationships

Abstract

Neutrophils have an important role in the self-defense systems of organisms through the production of superoxide. On the other hand, it has been proposed that abnormal amounts of superoxide produced by neutrophils are a serious factor in tissue injury. A series of novel thiazole derivatives was prepared and evaluated inhibitory effect on superoxide production by human neutrophils in vitro. Among these compounds, 6-[2-(3,4-diethoxyphenyl)thiazol-4-yl]- pyridine-2-carboxylic acid (OPC-6535) was selected as one of the most promising compounds. The synthesis and structure-activity relationships of these compounds are reported herein. © 1995, American Chemical Society. All rights reserved.