Synthesis and Pharmacological Activities of Novel Bicyclic Thiazoline Derivatives as Hepatoprotective Agents. II. (7-Alkoxycarbonyl-2, 3, 5, 6-tetrahydropyrrolo[2, 1-b]thiazol-3-ylidene)acetamide Derivatives

Abstract

A series of exomethylenic bicyclic thiazoline derivatives (3a-i) was synthesized and evaluated for hepatoprotective activity against galactosamine-induced and monoclonal antibody-induced acute liver injuries in rats. The structure-activity relationships were investigated. Among the compounds synthesized, N-methyl-(7-isopropoxycarbonyl-6, 6-dimethyl-2, 3, 5, 6-tetrahydropyrrolo[2, 1-b]thiazol-3-ylidene)acetamide (3i) exhibited the most potent hepatoprotective activity. This compound suppressed galactosamine-induced hepatic injury at 100 mg/kg by oral administration and further prevented monoclonal antibody-induced hepatic injury at 30 mg/kg by intraperitoneal injection, as judged from the changes in serum transaminase activities.