Synthesis and biological evaluation of 4-(hydroxyimino)arylmethyl diarylpyrimidine analogues as potential non-nucleoside reverse transcriptase inhibitors against HIV

被引：33

作者：

Feng, Xiao-Qing ^{[1
]}

Zeng, Zhao-Sen ^{[1
]}

Liang, Yong-Hong ^{[1
]}

Chen, Fen-Er ^{[1
]}

Pannecouque, Christophe ^{[2
]}

Balzarini, Jan ^{[2
]}

De Clercq, Erik ^{[2
]}

机构：

[1] Fudan Univ, Dept Chem, Shanghai 200433, Peoples R China

[2] Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2010年 / 18卷 / 07期

基金：

中国国家自然科学基金;

关键词：

HIV; NNRTIs; SAR; DAPYs; ANTI-HIV-1; ACTIVITY; COLORIMETRIC ASSAY; ANTIVIRAL ACTIVITY; DAPY ANALOGS; WILD-TYPE; DESIGN; PYRIMIDIN-4(3H)-ONES; SERIES; SAR;

D O I：

10.1016/j.bmc.2010.03.007

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of novel diarylpyrimidine analogues featuring a hydroxyiminomethyl group between the pyrimidine scaffold and the aryl wing I have been synthesized and tested in MT-4 cells culture as non-nucleoside reverse transcriptase inhibitors against human immunodeficiency virus (HIV). Most of these new congeners exhibited moderate to excellent activity against wild-type virus with an EC50 value ranging from 0.569 mu M to 0.005 mu M. 4-(4-((Hydroxyimino) (3-methoxyphenyl) methyl)pyrimidin-2-ylamino) benzonitrile (12n) was identified as the most active compound of this new series (EC50 = 0.025 mu M, SI > 1223) associated with moderate activity against HIV-1 double mutant strains (K103N + Y181C) (EC50 = 8.72 mu M) in addition to its anti-HIV-2 activity with an EC50 value of 8.31 mu M. Preliminary structure-activity relationship (SAR) among the newly synthesized DAPYs was also investigated. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：2370 / 2374

页数：5

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