Computer-aided design of non-nucleoside inhibitors of HIV-1 reverse transcriptase

被引：99

作者：

Jorgensen, WL

Ruiz-Caro, J

Tirado-Rives, J

Basavapathruni, A

Anderson, KS

Hamilton, AD

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 | 2006年 / 16卷 / 03期

关键词：

NNRTI; structure-based drug design; anti-HIV drugs; computer-aided drug design;

D O I：

10.1016/j.bmcl.2005.10.038

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Design principles are delineated for non-nucleoside inhibitors for HIV-1 reverse transcriptase (NNRTIs). Simultaneous optimization of binding affinity for wild-type RT, tolerance for viral mutations, and physical properties is pursued. Automated lead generation with the growing program BOMB, Monte Carlo simulations with free-energy perturbation theory for lead optimization, and property analysis with QikProp are featured. An initial 30 mu M lead has been optimized rapidly to the 10 nM level. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：663 / 667

页数：5

共 14 条

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