Synthesis and structure-activity relationship of novel diarylpyrimidines with hydromethyl linker (CH(OH)-DAPYs) as HIV-1 NNRTIs.
Synthesis and structure-activity relationship of novel diarylpyrimidines with hydromethyl linker (CH(OH)-DAPYs) as HIV-1 NNRTIs.
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DOI：
10.1016/j.bmc.2011.07.023
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发表时间：
2011-09
影响因子：
3.5
通讯作者：
Shuang‐Xi Gu;Qiu-Qin He;Shi-qiong Yang;Xiaodong Ma;Fener Chen;E. De Clercq;J. Balzarini;C. Pannecouque
中科院分区：
文献类型：
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作者：
Shuang‐Xi Gu;Qiu-Qin He;Shi-qiong Yang;Xiaodong Ma;Fener Chen;E. De Clercq;J. Balzarini;C. Pannecouque
合成了一系列以左苯环与中心嘧啶之间的羟基甲基连接为特征的26种二芳基嘧啶，并对其体外抗hiv活性进行了评价。大多数化合物对野生型HIV-1表现出中等到优异的活性。其中，左苯环C-2位含一个氯原子的化合物10i对野生型HIV-1具有较强的抑制活性，ec50值为0.009 μM；对双RT突变体（K103N + Y181C） HIV-1（IIIB）和HIV-2（ROD）具有较强的抑制活性，ec50值分别为6.2和6.0 μM。并初步研究了该化合物的构效关系。
A series of 26 diarylpyrimidines, characterized by the hydroxymethyl linker between the left wing benzene ring and the central pyrimidine, were synthesized and evaluated for in vitro anti-HIV activity. Most of the compounds exhibited moderate to excellent activities against wild-type HIV-1. Among them, compound10i, bearing a chlorine atom at the C-2 position of left benzene ring, was the best congener and showed potent activity against wild-type HIV-1 with an EC50value of 0.009 μM, along with moderate activities against the double RT mutant (K103N + Y181C) HIV-1(IIIB) and HIV-2(ROD) with an EC50value of 6.2 and 6.0 μM, respectively. The preliminary structure–activity relationship (SAR) of this new series of compounds was also investigated.