Synthesis and pharmacological activities of novel bicyclic thiazoline derivatives as hepatoprotective agents. I. 8-Ethoxycarbonyl-5,6-dihydrothiazolo[2,3-c][1,4]thiazine derivatives.

A series of bicyclic thiazoline derivatives (4a-s) 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, ethyl 3-(N-methylcarbamoyl)-5,6-dihydrothiazolo[2,3-c][1,4]thiazin e-8- carboxylate (4p) exhibited remarkable hepatoprotective activity and lower toxicity. This compound suppressed galactosamine-induced hepatic injury at 100 mg/kg by gavage and further prevented monoclonal antibody-induced hepatic injury at 30 mg/kg by intraperitoneal injection, as evaluated by measuring changes in serum transaminase activities.