Pyrimidine sulfonylacetanilides with improved potency against key mutant viruses of HIV-1 by specific targeting of a highly conserved residue
Pyrimidine sulfonylacetanilides with improved potency against key mutant viruses of HIV-1 by specific targeting of a highly conserved residue
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通过特异性靶向高度保守的残基，嘧啶磺酰乙酰苯胺提高了对抗 HIV-1 关键突变病毒的效力
DOI：
10.1016/j.ejmech.2015.08.007
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发表时间：
2015
影响因子：
6.7
通讯作者：
Pannecouque Christophe
中科院分区：
文献类型：
--
作者：
Wan Zheng-Yong;Yao Jin;Mao Tian-Qi;Wang Xin-Long;Wang Hai-Feng;Chen Wen-Xue;Yin Hong;Chen Fen-Er;De Clercq Erik;Daelemans Dirk;Pannecouque Christophe
基于分子模拟，优化了我们小组先前公开的依曲韦林-VRX-480773杂合体，以产生新的嘧啶磺酰乙酰苯胺8，其对一组7种临床相关的HIV-1单突变株和双突变株的活性有所改善。这种HIV RNA复制体外模型中效力的提高部分验证了这类变构嘧啶衍生物抑制逆转录酶（RT）的机制，并代表了抗HIV药物开发的显著进步。
Based on molecular simulation, the etravirine–VRX-480773 hybrids previously disclosed by our group were optimized to yield novel pyrimidine sulfonylacetanilides8with improved activity against a panel of seven clinically relevant single and double mutant strains of HIV-1. The improvement in potency in thisin vitromodel of HIV RNA replication partly validates the mechanism by which this class of allosteric pyrimidine derivatives inhibits the reverse transcriptase (RT), and represents a remarkable step forward in the development of anti-HIV drugs.