Ueda H, Momoi Y, Ikeda T, Kakegawa H, Miyataka H, Matsumoto H, Satoh T
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Japan.
Chem Pharm Bull (Tokyo). 1993 Mar;41(3):522-4. doi: 10.1248/cpb.41.522.
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.
合成了一系列新型的反式胍基甲基环己烷羧酸（trans-GMCHA）芳基酰胺。几种反式GMCHA芳基酰胺衍生物对大鼠应激和盐酸-乙醇诱导的胃溃疡的抑制作用比西曲酸更强。在小鼠急性毒性研究中，大多数酰胺显示出如此严重的毒性，以至于所有注射这些化合物（50mg/kg，腹腔注射）的小鼠都死亡了。然而，注射了在苯环上带有烷氧羰基的反式GMCHA（2'-、3'-和4'-乙氧基羰基）苯基酰胺（7、8和9）的小鼠存活了下来。根据这些结果，选择反式GMCHA（2'-乙氧基羰基）苯基酰胺（7）作为一种有前景的抗溃疡药物。
