Synthesis and biological evaluation of novel 6-substituted 5-alkyl-2-(arylcarbonylmethylthio)pyrimidin-4(3H)-ones as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
Synthesis and biological evaluation of novel 6-substituted 5-alkyl-2-(arylcarbonylmethylthio)pyrimidin-4(3H)-ones as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
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DOI：
10.1016/j.bmc.2008.01.039
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发表时间：
2008-04
影响因子：
3.5
通讯作者：
Yueping Wang;Fener Chen;E. De Clercq;J. Balzarini;C. Pannecouque
中科院分区：
文献类型：
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作者：
Yueping Wang;Fener Chen;E. De Clercq;J. Balzarini;C. Pannecouque
合成了一系列新的2-芳羰基甲硫基-6-芳甲基嘧啶-4（3 H）-酮类化合物，并在MT-4细胞中评价了其体外抗HIV活性。这些新化合物对野生型HIV-1具有中等至强效的活性，EC 50范围为8.97μM至0.010μM。其中，6-（3，5-二甲基苄基）类似物5 p被鉴定为最有希望的化合物（EC 50 =0.010μM，SI> 31，800），其对HIV-1双突变RT株K103 N + Y181 C具有中等活性。对这些新同系物的构效关系进行了讨论。
A novel series of 2-arylcarbonylmethylthio-6-arylmethylpyrimidin-4(3H)-ones have been synthesized and evaluated for in vitro anti-HIV activities in MT-4 cells. Most of these new compounds showed moderate to potent activities against wild-type HIV-1 with an EC50range from 8.97μM to 0.010μM. Among them, the 6-(3,5-dimethylbenzyl) analogue 5p was identified as the most promising compound (EC50=0.010μM, SI>31,800) associated with moderate activity against the HIV-1 double mutant RT strain K103N+Y181C. The structure–activity relationships of these new congeners were further discussed.