对位取代苯胺形成P－450－MI络合物构效关系的判别分析研究

本文测定了一组对位取代苯胺与未经处理或经苯巴比妥诱导的大鼠肝微粒体形成细胞色素Ｐ－４５０代谢中间体络合物的活性，并用Ｆｉｓｈｅｒ线性判别分析研究了它们的构效关系。结果表明，除４，４＇－二氨基二苯醚与经苯巴比妥诱导的大鼠肝微粒体形成细胞色素Ｐ－４５０代谢中间体络合物的活性被错分外，其余的对位取代苯胺均被正确分类；脂溶性较大和拉电子能力较强的对位取代基对形成代谢中间体络合物有利；经苯巴比妥诱导的大鼠肝微粒体与对位取代苯胺形成代谢中间体络合物的活性较大。

STUDY ON STRUCTURE-ACTIVITY RELATIONSHIP OF P-SUBSTITUTED ANILINES IN FORMING CYTO CHROME P450 METABOLIC INTERMEDIATE COMPLEX SING DISCRIMINANT ANALYSIS METHOD

A group of p-substituted anilines were tested on their activities to form cytochrome P450 metabolic intermediate complexes with untreated or phenobarbital-induced rat hepatic microsomes. The Fisher's linear discriminant analysis method was used to study their structure-activity relationship. Results showed that the p-substituted anilines were correctly categorized except for 4,4'-diamino-diphenyl ether which interacted with phenobarbital-induced rat hepatic microsomes. The p-substituted anilines with greater lipophilicity and stronger electron drawing facilitated the formation of cytochrome P450 metabolic intermediate complex. The rat hepatic microsome induced by phenobarbital had greater activity in forming cytochrome P450 metabolic intermediate complex with p-substituted aniline than untreated rat hepatic microsome.