抗消化性溃疡病药物杂环甲醛缩N4-取代苯基氨(硫)脲的合成和定量构效分析

按类型衍化出的先导物结构,经逐步调整苯环上取代基的电性和疏水性,合成了45个呋喃、吡咯和N-甲基吡咯-α-甲醛缩N⁴-3-,或4-取代的苯基氨脲和氨硫脲。对抗溃疡作用和毒性作用的定量评价及构效分析表明,活性与疏水性呈抛物线关系;引入推电子基团,有利于抗溃疡活性。化合物17和30的活性与毒性的分离较大,其药理作用在深入研究中。

STUDIES ON ANTIPEPTIC ULCER AGENTS:THE SYNTHESIS AND QSAR ANALYSIS OF HETEROCYCLE ALDEHYDE N4-SUBSTITUTED PHENYL(THIO)SEMICARBAZONES

Forty-five condensation products of furan-, pyrrole-, and N-methyl pyrrole-alpha-carboaldehyde with N4-3-or 4-substituted phenyl semicarbazides and thiosemicarbazides were designed and synthesized to optimize the antiulcer activity. Quantitative structure-activity relationships reveal that in the series of semicarbazones increase in hydrophobicity of molecules and introduction of electron-repelling groups onto the phenyl ring raise the antiulcer activity; Generally, the activity of semicarbazones is higher than that of the corresponding thiosemicarbazones. The large spans between activity and toxicity of compounds No. 17 and 30 led to further investigation of pharmacological actions.