Synthesis and biological evaluation of novel amprenavir-based P1-substituted bi-aryl derivatives as ultra-potent HIV-1 protease inhibitors

被引：14

作者：

Yan, Jianwei ^{[2
]}

Huang, Ning ^{[1
]}

Li, Shukun ^{[2
]}

Yang, Liu-Meng ^{[1
]}

Xing, Weiqiang ^{[2
]}

Zheng, Yong-Tang ^{[1
]}

Hu, Youhong ^{[2
]}

机构：

[1] Chinese Acad Sci, Key Lab Anim Models & Human Dis Mech, Chinese Acad Sci & Yunnan Prov, Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China

[2] Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 05期

基金：

中国国家自然科学基金;

关键词：

HIV-1 protease inhibitors; Amprenavir; Darunavir biaryl compounds; Docking study; STRUCTURE-BASED DESIGN; TERTIARY-ALCOHOL; INSULIN-RESISTANCE; DISCOVERY; MORTALITY;

D O I：

10.1016/j.bmcl.2012.01.037

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of P1-substituted biaryl amprenavir derivatives was designed and synthesized. These compounds were evaluated for enzyme inhibition and antiviral activity in vitro. Several compounds showed highly efficient antiviral activity with EC50 values down to 0.10 nM, which are more potent than marketed HIV-1 protease inhibitors. Docking study indicated that 12c has similar binding mode to amprenavir with full occupancy in P1. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：1976 / 1979

页数：4

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