Synthesis and pharmacokinetic profile of highly deuterated brecanavir analogs

被引：13

作者：

Velthuisen, Emile J. ^{[1
]}

Baughman, Todd M. ^{[1
]}

Johns, Brian A. ^{[1
]}

Temelkoff, David P. ^{[1
]}

Weatherhead, Jason G. ^{[1
]}

机构：

[1] GlaxoSmithKline Res & Dev Ltd, Infect Dis Therapeut Area Unit, Res Triangle Pk, NC 27709 USA

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 63卷

关键词：

HIV; AIDS; Protease inhibitor; Ritonavir; Deuterium; Kinetic isotope effect; HIV PROTEASE INHIBITORS; DISCOVERY; DEUTERIUM; RITONAVIR; MECHANISM; TOXICITY; THERAPY;

D O I：

10.1016/j.ejmech.2013.02.001

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Several highly deuterated analogs of the HIV-1 protease inhibitor brecanavir have been prepared to study the effect of deuterium upon metabolic stability. The sites for deuterium incorporation were initially chosen to maximize the potential for a kinetic isotope effect; locations where C-H bond breaking is the rate limiting step. The analogs have been profiled in both in vitro and in vivo pharmacokinetic studies and the result will be described herein. (C) 2013 Elsevier Masson SAS. All rights reserved.

引用

页码：202 / 212

页数：11

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