Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency

被引：14

作者：

Bollini, Mariela ^{[1
]}

Gallardo-Macias, Ricardo ^{[1
]}

Spasov, Krasimir A. ^{[2
]}

Tirado-Rives, Julian ^{[1
]}

Anderson, Karen S. ^{[2
]}

Jorgensen, William L. ^{[1
]}

机构：

[1] Yale Univ, Dept Chem, New Haven, CT 06520 USA

[2] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06520 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 04期

关键词：

Anti-HIV agents; Computer-aided drug design; NNRTIs; Free-energy calculations; DISCOVERY; EFFICIENT; DRUG; SEARCH; DESIGN; NNRTIS; AZOLES; VIRUS; CURE;

D O I：

10.1016/j.bmcl.2012.11.115

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved activity towards Tyr181Cys containing variants was pursued with the assistance of free energy perturbation (FEP) calculations. Optimization of the 4-R substituent in 1 led to ethyl and isopropyl analogs le and if with 1-7 nM potency towards both the wild-type virus and a Tyr181C variant. (C) 2012 Elsevier.Ltd. All rights reserved.

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收藏

页码：1110 / 1113

页数：4

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