Hybrid chemistry. Part 4: Discovery of etravirine-VRX-480773 hybrids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors
Hybrid chemistry. Part 4: Discovery of etravirine-VRX-480773 hybrids as potent HIV-1 non-nucleoside reverse transcriptase inhibitors
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混合化学。
DOI：
10.1016/j.bmc.2015.06.048
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发表时间：
2015-08-01
影响因子：
3.5
通讯作者：
Pannecouque, Christophe
中科院分区：
文献类型：
--
作者：
Wan, Zheng-Yong;Tao, Yuan;Pannecouque, Christophe
采用结构引导分子杂交策略，融合etravirine和VRX-480773药效团模板，设计了一系列新的etravirine-VRX-480773杂种。在MT-4细胞培养中评估其抗hiv -1活性和细胞毒性。该系列中活性最高的杂化化合物N-（2-氯苯基）-2-（（4-（4-氰基-2,6-二甲基苯氧基）嘧啶-2-基）硫代）乙酰胺3d （EC50 = 0.24, SI > 1225）在体外抗hiv -1细胞实验中比delavirdine （EC50 = 0.66 μ M, SI > 67）更有效。结构-活性关系的研究建立了抗hiv活性与乙酰苯胺基团取代模式之间的相关性。(C) 2015 Elsevier Ltd.版权所有。
A novel series of etravirine-VRX-480773 hybrids were designed using structure-guided molecular hybridization strategy and fusing the pharmacophore templates of etravirine and VRX-480773. The anti-HIV-1 activity and cytotoxicity was evaluated in MT-4 cell cultures. The most active hybrid compound in this series, N-(2-chlorophenyl)-2-((4-(4-cyano-2,6-dimethylphenoxy) pyrimidin-2-yl) thio) acetamide 3d (EC50 = 0.24, SI > 1225), was more potent than delavirdine (EC50 = 0.66 mu M, SI > 67) in the anti-HIV-1 in vitro cellular assay. Studies of structure-activity relationships established a correlation between anti-HIV activity and the substitution pattern of the acetanilide group. (C) 2015 Elsevier Ltd. All rights reserved.