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

抄録

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]thiazine-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.