Department of Chemistry, Korea University, Seoul 02841, Korea (ROK).
Mini Rev Med Chem. 2024;24(20):1822-1833. doi: 10.2174/0113895575308674240415074629.
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 structureproperty 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.
类药性在药物的吸附、分布、代谢、排泄和毒性中起着关键作用。因此，有效地优化这些性质对于新疗法的成功开发至关重要。了解已批准临床药物的结构-性质关系可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，从药物化学文献中编译了 9 种药物的结构-性质关系，其中不仅报告了最终药物的药代动力学和/或物理化学性质的详细信息，还报告了其在药物开发过程中生成的关键类似物的详细信息。总结了 9 种新批准药物的结构-性质关系，包括 3 种激酶抑制剂和 3 种 G 蛋白偶联受体拮抗剂。一些优化策略，如生物等排替换和立体位阻安装，成功地产生了具有增强的物理化学和药代动力学性质的临床候选药物。总结的结构-性质关系表明，适当的结构修饰如何有效地改善整体类药性。对已批准临床药物结构-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。
