12种取代苯胺形成P450－MI组合物的定量结构与活性关系

QUANTITATIVE STRUCTURE-ACTIVITY RELATION SHIPS OF 12 SUBSTITUTED ANILINES FOR THEIR ACTIVTIES IN P450-MI COMPLEX FORMATION

本文用逐步多元回归分析法导出了１２种取代苯胺的Ｈａｎｓｃｈ理化参数与取代苯胺形成细胞色素Ｐ４５０（简称Ｐ４５０）─代谢中间体（简称ＭＩ）络合物能力的定量结构与活性关系（ＱＳＡＫ）的相关方程式。结果表明，取代基的电性参数之和Σσ、脂溶性参数之和Σπ与形成Ｐ４５０－ＭＩ络合物的活性大小具有较好的相关性。对位存在含孤对电子的取代基使活性增大。本文还用分子轨道法ＭＮＤＯ－ＰＭ３计算了这些化合物的电子结构参数，没有得到具有统计意义的电子结构参数与活性之间的定量相关方程式。

Stepwise multiple regressive analysis was employed to generate quantitative structure-activity relationships between the activities of12 substituted anilines to form cytochrome P450 metabolic intermediate(P450-MI)comlex and Hansch's physico-chemical parameters of their substituents.The results showed that the activities to form P450-MI complex werew ell correlated with the sum of the electronic parameters Σσ and the sum of the hydrophobic parameters Σπ of their substituents. A lonely-paired electron donating group existing in the para-substituent would enhance the activity to form P450-MI complex.Molecular orbital calculations were adopted to determine the electronic structures of l2 substituted anilines investigated,but no statistically significant correlations were observed between the elctronic structural parameters and the activities in P450-MIcomplex formation.