Syntheses and inhibitory effects on gastric lesions of trans-guanidinomethylcyclohexane carboxylic acid arylamides.
A novel series of trans-guanidinomethylcyclohexanecarboxylic acid (trans-GMCHA) arylamides was synthesized. The several trans-GMCHA arylamide derivatives showed more potent inhibitory effects on the stress- and HCl-ethanol-induced gastric ulcers than cetraxate in rats. In acute toxicity studies in mice, most amides showed such severe toxicity that all mice injected with these compounds (50 mg/kg, i.p.) died. However, mice injected with the trans-GMCHA (2'-,3'- and 4'-ethoxycarboxy)phenylamide (7, 8 and 9) which bear an alkyloxycarbonyl group at benzene ring survived. From these results, trans-GMCHA (2'-ethoxycarbonyl)phenylamide (7) was selected as a promising anti-ulcer agent.
Ueda
H
H
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
Momoi
Y
Y
Ikeda
T
T
Kakegawa
H
H
Miyataka
H
H
Matsumoto
H
H
Satoh
T
T
D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D001565:Benzoates / Q000494:pharmacology; D002224:Carbanilides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D002927:Cimetidine / Q000494:pharmacology; D003509:Cyclohexanecarboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D005753:Gastric Mucosa / Q000187:drug effects*; D006146:Guanidines / Q000494:pharmacology; D008297:Male; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000188:drug therapy*; D013312:Stress, Physiological; D014148:Tranexamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D014361:Trypsin Inhibitors
D000897:Anti-Ulcer Agents; D001565:Benzoates; D002224:Carbanilides; D003509:Cyclohexanecarboxylic Acids; D006146:Guanidines; D014361:Trypsin Inhibitors; C000665:cetraxate; D014148:Tranexamic Acid; D002927:Cimetidine; D010196:Pancreatic Elastase; C057164:benexate