N-乙基-N-甲基苯胺的立体选择性微粒体N-氧化作用。

Stereoselective microsomal N-oxidation of N-ethyl-N-methylaniline.

作者信息

Hadley M R, Oldham H G, Camilleri P, Murphy J, Hutt A J, Damani L A

机构信息

Chelsea Department of Pharmacy, King's College London, U.K.

出版信息

Biochem Pharmacol. 1993 May 5;45(9):1739-42. doi: 10.1016/0006-2952(93)90428-y.

DOI:10.1016/0006-2952(93)90428-y

PMID:8494531

Abstract

The stereoselectivity of metabolic N-oxidation of N-ethyl-N-methylaniline (EMA) was investigated in vitro following incubation of the compound (1mM) with fortified hepatic microsomal preparations of both male Wistar rats and New Zealand White (NZW) rabbits. The major metabolites in both species were found to be N-ethylaniline, N-methylaniline and EMA N-oxide. Chromatographic resolution of the N-oxide enantiomers was achieved using a Chiralcel OD stationary-phase with a mobile-phase of hexane:ethanol (98:2, v/v). Examination of the enantiomeric composition of the N-oxide metabolites indicated a predominance of the (-)-(S)-N-oxide from both species with enantiomeric excesses of 52 +/- 2.5% and 65 +/- 2.1% (n = 3) in rat and rabbit tissue respectively. These preliminary observations indicate that the N-oxidation of EMA shows product stereoselectivity, the extent of which varies between species.

摘要

在体外，将化合物N-乙基-N-甲基苯胺（EMA，1 mM）与雄性Wistar大鼠和新西兰白兔（NZW）的强化肝微粒体制剂一起孵育后，研究了EMA代谢N-氧化的立体选择性。在这两个物种中发现的主要代谢产物是N-乙基苯胺、N-甲基苯胺和EMA N-氧化物。使用Chiralcel OD固定相和己烷：乙醇（98:2，v/v）流动相实现了N-氧化物对映体的色谱分离。对N-氧化物代谢产物对映体组成的检查表明，两个物种中均以（-）-（S）-N-氧化物为主，大鼠和兔组织中的对映体过量分别为52±2.5%和65±2.1%（n = 3）。这些初步观察结果表明，EMA的N-氧化显示出产物立体选择性，其程度在不同物种之间有所不同。