Metabolism of a new neuroprotective agent for ischemia-reperfusion damage, KR-31543 in the rats using liquid chromatography/electrospray mass spectrometry

被引：5

作者：

Kim, J

Ji, HY

Lee, SS

Yoo, SE

Kim, SO

Lee, DH

Lim, H

Lee, HS ^{[1
]}

机构：

[1] Wonwang Univ, Coll Pharm, Drug Metab & Bioanal Lab, Iksan 570749, South Korea

[2] Wonwang Univ, Coll Pharm, Drug Metab & Bioanal Lab, Iksan 570749, South Korea

[3] Univ British Columbia, Fac Pharmaceut Sci, Vancouver, BC V6T 1Z3, Canada

[4] Korea Res Inst Chem Technol, Taejon 305606, South Korea

[5] Dongbu Hannog Chem Co, Agropharma Res Inst, Taejon 305308, South Korea

来源：

ARCHIVES OF PHARMACAL RESEARCH | 2002年 / 25卷 / 05期

关键词：

KR-31543; LC/MS/MS; metabolism; CYP; neuroprotective;

D O I：

10.1007/BF02976941

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

KR-31543,(2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl -2H-1-benzopyran is a new neuroprotetive agent for ischemia-reperfusion damage. The in vitro and in vivo metabolism of KR-31543 in rats has been studied by LC-electrospray mass spectrometry. Rat liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of a metabolite M1. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC-MS/MS analysis with the synthesized authentic standard. Rat CYP3A1 and 3A2 are the major CYP isozymes involved in the formation of M1.

引用

页码：664 / 668

页数：5

共 3 条

[1] Clinical trials with neuroprotective drugs in acute ischaemic stroke: are we doing the right thing? [J].