6-Benzoyl-3-hydroxypyrimidine-2,4-diones as dual inhibitors of HIV reverse transcriptase and integrase

被引：42

作者：

Tang, Jing ^{[1
]}

Maddali, Kasthuraiah ^{[2
]}

Dreis, Christine D. ^{[1
]}

Sham, Yuk Y. ^{[1
]}

Vince, Robert ^{[1
]}

Pommier, Yves ^{[2
]}

Wang, Zhengqiang ^{[1
]}

机构：

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

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 08期

关键词：

HIV; 6-Benzoyl-3-hydroxypyrimidine-2,4-diones; Dual inhibitors; Reverse transcriptase; Integrase; NONNUCLEOSIDE INHIBITORS; PHARMACOPHORE MODEL; ANTI-HIV-1; ACTIVITY; DESIGN; PYRIMIDINEDIONES; STRATEGIES; ADHERENCE; UPDATE; HAART;

D O I：

10.1016/j.bmcl.2011.02.069

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

N-3-Hydroxylation of pyrimidine-2,4-diones was recently found to yield inhibitors of both HIV-1 reverse transcriptase (RT) and integrase (IN). An extended series of analogues featuring a benzoyl group at the C-6 position of the pyrimidine ring was synthesized. Through biochemical studies it was found that these new analogues are dually active against both RT and IN in low micromolar range. Antiviral assays confirmed that these new inhibitors are active against HIV-1 in cell culture at nanomolar to low micromolar range, further validating 3-hydroxypyrimidine-2,4-diones as a viable scaffold for antiviral development. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：2400 / 2402

页数：3

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