Ueda H, Ikeda T, Kakegawa H, Miyataka H, Matsumoto H, Satoh T
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
Chem Pharm Bull (Tokyo). 1993 Aug;41(8):1387-90. doi: 10.1248/cpb.41.1387.
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.
合成了一系列新型的4-胍基甲基苯甲酸（GMBA）芳基酰胺。其中几种对大鼠应激性胃损伤的抑制作用比西曲酸更强。我们选择4-胍基甲基苯甲酸（2'-乙氧羰基）苯酰胺3进行进一步的药理学评估，因为它毒性较低。化合物3对应激、盐酸-乙醇和吲哚美辛诱导的胃损伤及胃分泌均有显著抑制作用，其半数有效剂量（ED50）值分别为34.4、45.0和23.0 mg/kg（口服）以及240 mg/kg（皮内注射）。此外，该化合物能恢复应激负荷导致的胃黏液减少，并抑制化合物48/80诱导的溃疡。
