Syntheses and inhibitory effects on gastric lesions of 4-guanidinomethylbenzoic acid arylamides.
A novel series of 4-guanidinomethylbenzoic acid (GMBA) arylamides was synthesized. Several showed more potent inhibitory effects on stress-induced gastric lesion in rats than cetraxate. We selected 4-guanidinomethylbenzoic acid (2'-ethoxycarbonyl)phenylamide 3 for further pharmacological assessments because it had low toxicity. Compound 3 showed significant inhibitory effects on stress-, HCl-ethanol- and indomethacin-induced gastric lesions and gastric secretion, the ED50 values being 34.4, 45.0 and 23.0 mg/kg (p.o.) and 240 mg/kg (i.d.), respectively. Furthermore, this compound restored the reduction of gastric mucus caused by the stress-loading and inhibited compound 48/80-induced ulcer.
Ueda
H
H
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
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; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control*; D013315:Stress, Psychological / Q000150:complications; D014148:Tranexamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D001549:Benzamides; D006146:Guanidines; C000665:cetraxate; D014148:Tranexamic Acid