1H-1,2,4-三唑基二苯甲酮衍生物450191-S在犬血浆中的N-羟甲基代谢产物。

N-hydroxymethyl metabolites of 450191-S, a 1H-1,2,4,-triazolyl benzophenone derivative, in dog plasma.

作者信息

Koike M, Norikura R, Futaguchi S, Yamaguchi T, Sugeno K, Iwatani K, Ikenishi Y, Nakagawa Y

出版信息

Drug Metab Dispos. 1987 May-Jun;15(3):426-8.

Abstract

In a metabolic experiment of 5-[(2-aminoacetamido)methyl]-1-[4-chloro-2-(o-chlorobenzoyl)phenyl ]-N, N-dimethyl-1H-1,2,4,-triazole-3-carboxamide hydrochloride dihydrate (450191-S) in dogs, two new metabolites 8-chloro-6-(o-chlorophenyl)-N-hydroxymethyl-4H-1,2,4-triazolo [1,5-a] [1,4]benzodiazepine-2-carboxamide (M-A) and 8-chloro-6-(o-chlorophenyl)-N-hydroxymethyl-N-methyl-4H-1,2,4-triazolo [1,5-a] [1,4]benzodiazepine-2-carboxamide (M-D) in plasma were found in addition to 8-chloro-6-(o-chlorophenyl)-N,N-dimethyl-4H-1,2,4-triazolo[1,5-a] [1,4] benzodiazepine-2-carboxamide (M-1), 8-chloro-6-(o-chlorophenyl)-N-methyl-4H-1,2,4-triazolo[1,5-a] [1,4] benzodiazepine-2-carboxamide (M-2), 8-chloro-6-(o-chlorophenyl)-4H-1,2,4-triazolo-[1,5-a] [1,4] benzodiazepine-2-carboxamide (M-3), and 8-chloro-6-(o-chlorophenyl)-4H-1,2,4-triazolo[1,5-a] [1,4] benzodiazepine-2-carboxylic acid (M-4). The structures of N-hydroxymethyl metabolites were elucidated mainly by mass spectrometry. The structures were confirmed by synthesizing the authentic compounds and comparing the mass spectra.

摘要

在对犬进行的5-[(2-氨基乙酰氨基)甲基]-1-[4-氯-2-(邻氯苯甲酰基)苯基]-N,N-二甲基-1H-1,2,4-三唑-3-甲酰胺盐酸盐二水合物（450191-S）的代谢实验中，除了8-氯-6-(邻氯苯基)-N,N-二甲基-4H-1,2,4-三唑并[1,5-a][1,4]苯并二氮杂卓-2-甲酰胺（M-1）、8-氯-6-(邻氯苯基)-N-甲基-4H-1,2,4-三唑并[1,5-a][1,4]苯并二氮杂卓-2-甲酰胺（M-2）、8-氯-6-(邻氯苯基)-4H-1,2,4-三唑并[1,5-a][1,4]苯并二氮杂卓-2-甲酰胺（M-3）和8-氯-6-(邻氯苯基)-4H-1,2,4-三唑并[1,5-a][1,4]苯并二氮杂卓-2-羧酸（M-4）外，还在血浆中发现了两种新的代谢产物8-氯-6-(邻氯苯基)-N-羟甲基-4H-1,2,4-三唑并[1,5-a][1,4]苯并二氮杂卓-2-甲酰胺（M-A）和8-氯-6-(邻氯苯基)-N-羟甲基-N-甲基-4H-1,2,4-三唑并[1,5-a][1,4]苯并二氮杂卓-2-甲酰胺（M-D）。N-羟甲基代谢产物的结构主要通过质谱法阐明。通过合成 authentic 化合物并比较质谱图对结构进行了确认。