Abstract：
Drug-like properties play pivotal roles in drug adsorption, distribution, metabolism, excretion, and toxicity. Therefore, efficiently optimizing these properties is essential for the successful development of novel therapeutics. Understanding the structure-property relationships of clinically approved drugs can provide valuable insights for drug design and optimization strategies. Among the new drugs approved in 2023, which include 31 small-molecule drugs in the US, the structure-property relationships of nine drugs were compiled from the medicinal chemistry literature, in which detailed information on pharmacokinetic and/or physicochemical properties was reported not only for the final drug but also for its key analogs generated during drug development. The structure-property relationships of nine newly approved drugs are summarized, including three kinase inhibitors and three G-protein-coupled receptor antagonists. Several optimization strategies, such as bioisosteric replacement and steric handle installation, have successfully produced clinical candidates with enhanced physicochemical and pharmacokinetic properties. The summarized structure-property relationships demonstrate how appropriate structural modifications can effectively improve overall drug-like properties. The ongoing exploration of structure- property relationships of clinically approved drugs is expected to offer valuable guidance for developing future drugs.
摘要：
药物样特性在药物吸附中起关键作用，分布，新陈代谢，排泄,和毒性。因此,有效地优化这些特性对于成功开发新型疗法至关重要。了解临床批准药物的结构-性质关系可以为药物设计和优化策略提供有价值的见解。在2023年批准的新药中，包括美国的31种小分子药物，九种药物的结构-性质关系来自药物化学文献，其中不仅报告了最终药物的药代动力学和/或理化性质的详细信息，还报告了药物开发过程中产生的关键类似物的详细信息。总结了九种新批准药物的结构-性质关系，包括三种激酶抑制剂和三种G蛋白偶联受体拮抗剂。几种优化策略，如生物等排置换和空间手柄安装，已成功生产出具有增强的物理化学和药代动力学特性的临床候选物。总结的结构-性质关系证明了适当的结构修饰如何有效地改善整体药物样性质。对临床批准药物的结构-性质关系的持续探索有望为开发未来药物提供有价值的指导。
