Wang Han, Ma Xiaolong, Sun Longkang, Bi Tongyu, Yang Weibo
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China; School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China.
Bioorg Med Chem Lett. 2025 Apr 15;119:130096. doi: 10.1016/j.bmcl.2025.130096. Epub 2025 Jan 9.
The discovery of novel anticancer agents remains a critical goal in medicinal chemistry, with innovative synthetic methodologies playing a pivotal role in advancing this field. Recent breakthroughs in CH activation reactions, cyclization reactions, multicomponent reactions, cross-coupling reactions, and photo- and electro-catalytic reactions have enabled the efficient synthesis of new molecular scaffolds exhibiting potent biological activities, including anticancer properties. These methodologies have facilitated the functionalization of natural products, the modification of bioactive molecules, and the generation of entirely new compounds, many of which demonstrate strong antitumor activity. This review summarizes the latest synthetic strategies employed over the past five years for discovering anticancer agents, focusing on their influence on drug design. Additionally, the role of new chemical reactions in expanding chemical space and overcoming challenges, such as drug resistance and selectivity, is highlighted, further emphasizing the importance of discovering novel reactions as a key trend in future drug development.
新型抗癌药物的发现仍然是药物化学的一个关键目标,创新的合成方法在推动该领域发展中起着关键作用。碳氢键活化反应、环化反应、多组分反应、交叉偶联反应以及光催化和电催化反应的最新突破,使得能够高效合成具有强大生物活性(包括抗癌特性)的新分子骨架。这些方法促进了天然产物的功能化、生物活性分子的修饰以及全新化合物的生成,其中许多化合物表现出强大的抗肿瘤活性。本综述总结了过去五年用于发现抗癌药物的最新合成策略,重点关注它们对药物设计的影响。此外,还强调了新化学反应在拓展化学空间以及克服耐药性和选择性等挑战方面的作用,进一步凸显了发现新型反应作为未来药物开发关键趋势的重要性。