Design and synthesis of potent HIV-1 protease inhibitors incorporating hydroxyprolinamides as novel P2 ligands

被引：8

作者：

Gao, Bing-Lei ^{[1
]}

Zhang, Cheng-Mei ^{[1
]}

Yin, Yi-Zhen ^{[1
]}

Tang, Long-Qian ^{[1
]}

Liu, Zhao-Peng ^{[1
]}

机构：

[1] Shandong Univ, Sch Pharmaceut Sci, Jinan 250012, Shandong, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 12期

基金：

中国国家自然科学基金;

关键词：

HIV-1 protease inhibitors; Hydroxyprolinamide; P2; ligand; Drug-resistant; Design; Synthesis; DRUG-RESISTANCE; DISCOVERY; PROGRESS; BINDING; TMC114;

D O I：

10.1016/j.bmcl.2011.04.070

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of new HIV-1 protease inhibitors with the hydroxyethylamine core and different hydroxyprolinamide P2 ligands were designed and synthesized. Variation of substitutions at the P2 significantly affected the enzyme inhibitory potency of the inhibitors. Compounds 2a and 2d showed excellent enzyme inhibitory activity with IC50 values in the nanomolar range. An active site binding model for inhibitors 2a and 2d was suggested based upon the computational-docking results of the ligand with HIV-1 protease. This model offers molecular insights regarding ligand-binding site interactions of the hydroxyprolinamide-derived novel P2-ligand. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：3730 / 3733

页数：4

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