Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China; School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Zhengzhou University, Zhengzhou, 450001, China.
Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, 450018, China.
Eur J Med Chem. 2024 Nov 5;277:116759. doi: 10.1016/j.ejmech.2024.116759. Epub 2024 Aug 10.
In 2022, the U.S. Food and Drug Administration approved a total of 16 marketing applications for small molecule drugs, which not only provided dominant scaffolds but also introduced novel mechanisms of action and clinical indications. The successful cases provide valuable information for optimizing efficacy and enhancing pharmacokinetic properties through strategies like macrocyclization, bioequivalent group utilization, prodrug synthesis, and conformation restriction. Therefore, gaining an in-depth understanding of the design principles and strategies underlying these drugs will greatly facilitate the development of new therapeutic agents. This review focuses on the research and development process of these newly approved small molecule drugs including drug design, structural modification, and improvement of pharmacokinetic properties to inspire future research in this field.
2022 年，美国食品和药物管理局共批准了 16 个小分子药物的营销申请，这些申请不仅提供了主要的支架，还引入了新的作用机制和临床适应证。成功案例为通过大环化、生物等效基团利用、前药合成和构象限制等策略优化疗效和增强药代动力学性质提供了有价值的信息。因此，深入了解这些药物背后的设计原则和策略将极大地促进新治疗剂的开发。本综述重点介绍了这些新批准的小分子药物的研发过程，包括药物设计、结构修饰和改善药代动力学性质，以启发该领域的未来研究。
