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.
Hasegawa
M
M
Exploratory Research Laboratories III, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Nakayama
A
A
Hosokami
T
T
Kurebayashi
Y
Y
Ikeda
T
T
Shimoto
Y
Y
Ide
S
S
Honda
Y
Y
Suzuki
N
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000633:toxicity; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008107:Liver Diseases / Q000188:drug therapy; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis* / Q000494:pharmacology; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D013843:Thiazines; D013844:Thiazoles; C092686:ethyl 3-(N-methylcarbamoyl)-5,6-dihydrothiazolo(2,3-c)(1,4)thiazine-8-carboxylate