HIV-1包膜糖蛋白gp120小分子抑制剂的研究进展  

Advances in the research of HIV-1 envelope glycoprotein gp120 inhibitors

作　　者：谢明卉 汪昭 孙彦莹 姜向毅 展鹏[1] 刘新泳[1] 康东伟[1] XIE Ming-hui;WANG Zhao;SUN Yan-ying;JIANG Xiang-yi;ZHAN Peng;LIU Xin-yong;KANG Dong-wei(Institute of Medicinal Chemistry,Key Laboratory of Chemical Biology,School of Pharmaceutical,Shandong University,Jinan 250012,China)

机构地区：[1]山东大学药学院药物化学研究所,化学生物学教育部重点实验室,山东济南250012

出　　处：《药学学报》2023年第3期616-628,共13页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81903453,81973181);山东省优秀青年基金资助项目(ZR2020YQ61)。

摘　　要：人类免疫缺陷病毒1型(human immunodeficiency virus-1,HIV-1)包膜糖蛋白gp120与CD4的结合是病毒侵入细胞的第一步,干扰此过程就能阻止病毒识别靶细胞而抑制其复制,因此HIV-1 gp120作为HIV-1生命周期中的重要靶标,针对该靶标的药物已成为当前抗艾滋病药物研发的热点。其中,gp120小分子抑制剂BMS-626529经前药策略修饰后得到的磷酸酯前药福替沙韦(fostesavir)已分别于2020年和2021年被美国和欧洲批准上市用于治疗具有多重耐药性HIV-1感染的成年患者。该篇综述从药物化学的角度重点描述了靶向gp120-CD4相互作用环节的各种结构类型小分子抑制剂的研究进展,以期为gp120抑制剂的研究提供启发。From the process of human immunodeficiency virus-1(HIV-1)invading cells,the combination of gp120 and CD4 is the first step for HIV-1 to invade cells.Interfering with this process can prevent HIV from recognizing target cells and inhibit virus replication.Therefore,HIV-1 gp120 is an important part of the HIV-1 life cycle.Fostesavir,a phosphatate prodrug derived from the gp120 inhibitor BMS-626529 modified by the prodrug strategy,was approved for the treatment of adult patients with multidrug resistant HIV-1 infection by the US FDA and the European Medicines Agency in 2020 and 2021,respectively.In this review,we focus on the research progress of small molecule inhibitors targeting the interaction of gp120-CD4 from the perspective of medicinal chemistry,in order to provide reference for the subsequent research of gp120 inhibitors.

关 键 词：人类免疫缺陷病毒1型 侵入抑制剂 GP120 BMS-626529 NBD-14270 

分 类 号：R914[医药卫生—药物化学]