School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, PR China.
School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, 211198, PR China.
Eur J Med Chem. 2023 May 5;253:115338. doi: 10.1016/j.ejmech.2023.115338. Epub 2023 Apr 5.
Currently, bioorthogonal coupling reactions have garnered considerable interest due to their high substrate selectivity and less restrictive reaction conditions. During recent decades, bioorthogonal coupling reactions have emerged as powerful tools in drug development. This review describes the current applications of bioorthogonal coupling reactions in compound library building mediated by the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and in situ click chemistry or conjunction with other techniques; druggability optimization with 1,2,3-triazole groups; and intracellular self-assembly platforms with ring tension reactions, which are presented from the viewpoint of drug development. There is a reasonable prospect that bioorthogonal coupling reactions will accelerate the screening of lead compounds, the designing strategies of small molecules and expand the variety of designed compounds, which will be a new trend in drug development in the future.
目前，由于其高底物选择性和较少的限制反应条件，生物正交偶联反应引起了相当大的兴趣。在过去的几十年中，生物正交偶联反应已成为药物开发中的有力工具。本综述描述了生物正交偶联反应在铜催化的叠氮-炔环加成（CuAAC）反应介导的化合物库构建、原位点击化学或与其他技术结合、1,2,3-三唑基团的成药性优化以及环张力反应的细胞内自组装平台中的应用，从药物开发的角度进行了介绍。合理的前景是，生物正交偶联反应将加速先导化合物的筛选、小分子设计策略的扩展和设计化合物的多样性，这将成为未来药物开发的新趋势。
