A novel diketo phosphonic acid that exhibits specific, strand-transfer inhibition of HIV integrase and anti-HIV activity

被引：10

作者：

Chi, Guochen

Nair, Vasu ^{[1
]}

Semenova, Elena

Pommier, Yves

机构：

[1] Univ Georgia, Ctr Drug Discovery, Athens, GA 30602 USA

[2] Univ Georgia, Dept Pharmaceut & Biomed Sci, Athens, GA 30602 USA

[3] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 05期

关键词：

synthesis; phosphonates; HIV integrase inhibitors; mechanism of inhibition; anti-HIV activity;

D O I：

10.1016/j.bmcl.2006.12.009

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have synthesized novel phosphonic acid analogues of P-diketo acids. Interestingly, the phosphonic acid isostere, 2, of our anti-HIV compound, 1, was an inhibitor of only the strand transfer step, in stark contrast to 1. Compound 2 had lower anti-HIV activity than 1, but was more active and less toxic than the phosphonic acid analogue of L-708906. These isosteric compounds represent the first examples of beta-diketo phosphonic acids of structural, synthetic, and antiviral interest. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：1266 / 1269

页数：4

共 36 条

[1] HIV-1 integrase: Structural organization, conformational changes, and catalysis [J].