抗消化性溃疡病药物杂环甲醛缩氨(硫)脲和酰胺的合成和构效分析

呋喃唑酮是我国临床上发现并使用的抗消化道溃疡药物。为优化其活性,对呋喃唑酮分子中的硝基呋喃环和噁唑酮环进行了结构修饰和改造。合成的28个化合物的生物活性表明,用呋喃、噻吩、吡咯或甲基吡咯代替硝基呋喃环,用氮脲、氨硫脲和芳酰肼等结构片断替代噁唑酮环,均可引起活性和毒性的变化。构效关系分析表明,化合物的水溶解性和羰基的电荷密度是影响化合物活性的重要因素。

STUDIES ON ANTIPEPTIC ULCER AGENTS: THE SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIP ANALYSIS OF HETEROCYCLE ALDEHYDE (THIO) SEMICARBAZONES AND ACYL HYDRAZONES

Twenty-eight condensation products of heterocycle-alpha-carboaldehydes with N-aminooxazolidones, semicarbazides, thiosemicarbazides, aminoguanidines, aromatic hydrazides and benzoxycarbonyl hydrazide were synthesized so as to deduce the antiulcer pharmacophore or fragment of furazolidone(I), the prototype, which shows therapeutic efficacy for patients with gastric ulcer. Analysis of the SAR of the compounds indicate that the substitution of furan, thiophene, pyrrole and N-methyl pyrrole rings for the 5-nitrofuran and the cleavage of the oxazolidone ring obtain the activity to some extent. The necessary electronic density of carbonyl group of compounds is of importance. A lead structure, therefore, is derived for further optimization.