Synthesis and pharmacokinetic profile of highly deuterated brecanavir analogs

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• 作者：Emile J. Velthuisen ; ^{emile.j.velthuisen@gsk.com} ; Todd M. Baughman ; Brian A. Johns ; David P. Temelkoff ; Jason G. Weatherhead
• 关键词：HIV ; AIDS ; Protease inhibitor ; Ritonavir ; Deuterium ; Kinetic isotope effect
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：May, 2013
• 年：2013
• 卷：63
• 期：Complete
• 页码：202-212
• 全文大小：856 K

文摘

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.