摘要
本研究用不同来源的鼠肝微粒体,测定了40余种取代苯胺生成细胞色素P450代谢中问体(MI)络合物的能力,其结构与活性间关系可归纳如下:(1)在氨基的对位或间位必须存在一个可提供孤对电子的取代基,当此取代基位于邻位时,化合物不能生成P450-MI络合物,(2)在对位取代基中除了可提供孤对电子的基团外,引入亲脂性结构有助于生成P450-MI络合物,(3)间氯或对-氯邻甲苯胺似仅选择性地络合苯巴比妥与Aroclor共诱导的P450亚族,(4)苯环上若无可提供孤对电子的基团,任何疏水性,亲水性或供电子取代基均无助于取代苯胺生成P450-MI络合物。(5)一组可形成P450-MI络合物的取代苯胺(取代对氨基二苯醚)延长小鼠戊巴比妥睡眠时间的能力与取代基的电性相关。
More than 40 substituted anilines including 12 homologues were tested for their activities to form cytochrome P450 metabolic intermediate (P450-MI) complex from different sources of microsomes. The results showing the structure-activity relationship (SAR) in this respect can be presented as follows: (1) A lone-paired electron donating group must exist in the para- or meta- substituent, and a shift of such a group to the ortho-position would abolish its ability to form MI complex. (2) In addition to the lone-paired electron donating group a lipophilic moiety in the p-substituent would facilitate the MI complex formation. (3) meta- or para- chlorinated toluidines seem to selectively form complexes with phenobarbital and Aroclor co-induced P450. (4) If the lone-paired electron donating group is absent, any hydrophobic, hydrophilic or electron donating substituent would not facilitate the substituted anilines to form MI complex. (5) The ability of a group of substituted anilines which can form MI complex (substituted p-amino-diphenyl-ethers) to prolongate the pentobarbital sleeping time in mice is observed to be possibly correlated with electronic properties.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
1992年第3期161-165,共5页
Chinese Journal of Pharmacology and Toxicology
基金
国家自然科学基金 № 3880675
关键词
细胞色素
取代苯胺
结构活性关系
cytochrome P450 substituted anilines drug metabolism metabolic-intermediate complex structure-activity relationship
