Wan Zheng-Yong, Tao Yuan, Wang Ya-Feng, Mao Tian-Qi, Yin Hong, Chen Fen-Er, Piao Hu-Ri, De Clercq Erik, Daelemans Dirk, Pannecouque Christophe
Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China.
Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China; Institute of Biomedical Science, Fudan University, Shanghai 200433, People's Republic of China.
Bioorg Med Chem. 2015 Aug 1;23(15):4248-4255. doi: 10.1016/j.bmc.2015.06.048. Epub 2015 Jun 27.
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 μM, 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.
采用结构导向的分子杂交策略，融合依曲韦林和VRX-480773的药效团模板，设计了一系列新型的依曲韦林-VRX-480773杂合物。在MT-4细胞培养物中评估了其抗HIV-1活性和细胞毒性。该系列中活性最强的杂合化合物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细胞试验中比地拉韦啶（EC50=0.66 μM，SI>67）更有效。构效关系研究确定了抗HIV活性与乙酰苯胺基团取代模式之间的相关性。
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