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6-苯甲酰基-3-羟基嘧啶-2,4-二酮作为 HIV 逆转录酶和整合酶的双重抑制剂。

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

机构信息

Center for Drug Design, University of Minnesota, 516 Delaware St SE, Minneapolis, MN 55455, United States.

出版信息

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2400-2. doi: 10.1016/j.bmcl.2011.02.069. Epub 2011 Feb 18.

DOI:10.1016/j.bmcl.2011.02.069
PMID:21392991
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3070847/
Abstract

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.

摘要

嘧啶-2,4-二酮的 N-3-羟化作用最近被发现可生成 HIV-1 逆转录酶 (RT) 和整合酶 (IN) 的抑制剂。合成了一系列在嘧啶环的 C-6 位置带有苯甲酰基的扩展类似物。通过生化研究发现，这些新的类似物在低微摩尔范围内对 RT 和 IN 均具有双重活性。抗病毒测定证实，这些新的抑制剂在细胞培养物中对 HIV-1 的活性在纳摩尔至低微摩尔范围内，进一步验证了 3-羟基嘧啶-2,4-二酮作为抗病毒药物开发的可行支架。

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