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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Tang, Jing¹  Maddali, Kasthuraiah²  Dreis, Christine D.¹  Sham, Yuk Y.¹  Vince, Robert¹  Pommier, Yves²  Wang, Zhengqiang¹ 

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

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

关键词: HIV;    6-Benzoyl-3-hydroxypyrimidine-2,4-diones;    Dual inhibitors;    Reverse transcriptase;    Integrase;   

DOI  :  10.1016/j.bmcl.2011.02.069

来源: Elsevier

【 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.

【 授权许可】

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