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-ylidend) acetamid derivatives.
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-isopropoxy-carbonyl-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.
Hasegawa
M
M
Exploratory Research Laboratory III, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Nakayama
A
A
Yokohama
S
S
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; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury; D005688:Galactosamine / Q000633:toxicity; D008099:Liver / Q000187:drug effects; D008107:Liver Diseases / Q000517:prevention & control*; D051379:Mice; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D001643:Bridged Bicyclo Compounds; D013844:Thiazoles; D005688:Galactosamine