Discovery of potent HIV-1 protease inhibitors incorporating sulfoximine functionality

被引：39

作者：

Lu, Ding

Vince, Robert

机构：

[1] Univ Minnesota, Coll Pharm, Dept Med Chem, Minneapolis, MN 55455 USA

[2] Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, Minneapolis, MN 55455 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 20期

关键词：

HIV-1 protease inhibitor; C-2; symmetry; sulfoximine; transition state mimic;

D O I：

10.1016/j.bmcl.2007.07.095

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Based on the unique property of sulfoximine and the homodimeric Q structural symmetry of HIV-1 protease, a novel class of sulfoximine-based pseudosymmetric HIV-1 protease inhibitors was designed and synthesized. The sulfoximine moiety was demonstrated to be important for HIV-1 protease inhibitor potency. The most active stereoisomer (2S,2 ' S) displays a potency of 2.5 nM (IC50) against HIV-1 protease and an anti-HIV-1 activity of 408 nM (IC50). A possible mode of action is proposed. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：5614 / 5619

页数：6