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

Chem Pharm Bull (Tokyo). 1995 Jan;43(1):78-83. doi: 10.1248/cpb.43.78.

Abstract

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.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / toxicity
  • Liver / drug effects*
  • Liver / enzymology
  • Liver Diseases / drug therapy
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship
  • Thiazines / chemical synthesis*
  • Thiazines / pharmacology
  • Thiazoles / chemical synthesis*
  • Thiazoles / pharmacology

Substances

  • Antibodies, Monoclonal
  • Thiazines
  • Thiazoles
  • ethyl 3-(N-methylcarbamoyl)-5,6-dihydrothiazolo(2,3-c)(1,4)thiazine-8-carboxylate