Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012 Jinan, Shandong, PR China.
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012 Jinan, Shandong, PR China.
Eur J Med Chem. 2016 May 23;114:65-78. doi: 10.1016/j.ejmech.2016.02.051. Epub 2016 Feb 24.
CXCR4 plays vital roles in HIV-1 life cycle for it's essential in mediating the interaction of host and virus and completing the entry process in the lifecycle of HIV-1 infection. Compared with some traditional targets, CXCR4 provides a novel and less mutated drug target in the battle against AIDS. Its antagonists have no cross resistance with other antagonists. Great achievements have been made recent years and a number of small molecular CXCR4 antagonists with diversity scaffolds have been discovered. In this review, recent advances in the discovery of CXCR4 antagonists with special attentions on their evolution and structure-activity relationships of representative CXCR4 antagonists are described. Moreover, some classical medicinal chemistry strategies and novel methodologies are also introduced.
CXCR4 在 HIV-1 生命周期中发挥着至关重要的作用，因为它在介导宿主和病毒的相互作用以及完成 HIV-1 感染生命周期中的进入过程中是必不可少的。与一些传统靶点相比，CXCR4 为抗艾滋病斗争提供了一个新颖且突变较少的药物靶点。其拮抗剂与其他拮抗剂没有交叉耐药性。近年来取得了重大进展，发现了许多具有多样性骨架的小分子 CXCR4 拮抗剂。本文综述了 CXCR4 拮抗剂的发现进展，特别关注了代表性 CXCR4 拮抗剂的进化和构效关系，此外还介绍了一些经典的药物化学策略和新方法。
