Structure-Property Relationships Reported for the New Drugs Approved in 2024.

IF 3.3 3区 医学 Q2 CHEMISTRY, MEDICINAL
Kihang Choi
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引用次数: 0

Abstract

This mini-review summarizes the structure-property relationships of seven smallmolecule drugs approved in 2024, providing insights into effective lead-to-candidate optimization strategies. The analysis focused on aprocitentan, flurpiridaz F-18, inavolisib, vorasidenib, ensitrelvir, golidocitinib, and zorifertinib, highlighting the key structural modifications that enhanced their drug-like properties. Notable optimization strategies included the strategic use of five- and sixmembered nitrogen-containing heterocycles as cyclic bioisosteres and solubilizing groups. For the kinase inhibitor golidocitinib, the unique position of a solubilizing group within the binding pocket achieved dual benefits, i.e., enhanced target selectivity and physicochemical properties. When developing central nervous system-penetrant drugs such as zorifertinib, careful control of rotatable bonds, hydrogen bond donors, and molecular lipophilicity was critical for optimizing blood-brain barrier penetration while remaining suitable for oral administration. These findings on structureproperty relationships offer valuable guidance for future drug development, particularly in addressing challenges related to solubility, bioavailability, and tissue-specific drug distribution.

2024年获批新药的结构-性质关系报告。
这篇迷你综述总结了2024年批准的7种小分子药物的结构-性质关系,为有效的候选药物优化策略提供见解。分析重点是阿普昔坦、氟吡唑F-18、inavolisib、vorasidenib、ensitrelvir、golidocitinib和zorifertinib,强调了增强其药物样性质的关键结构修饰。值得注意的优化策略包括战略性地使用五元和六元含氮杂环作为环生物异构体和增溶基团。对于激酶抑制剂golidocitinib来说,在结合口袋内的独特位置实现了双重好处,即增强了靶标选择性和物理化学性质。在开发中枢神经系统渗透药物(如zorifertinib)时,仔细控制可旋转键、氢键供体和分子亲脂性是优化血脑屏障穿透的关键,同时仍然适合口服给药。这些关于结构性质关系的发现为未来的药物开发提供了有价值的指导,特别是在解决与溶解度、生物利用度和组织特异性药物分布相关的挑战方面。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
7.80
自引率
0.00%
发文量
231
审稿时长
6 months
期刊介绍: The aim of Mini-Reviews in Medicinal Chemistry is to publish short reviews on the important recent developments in medicinal chemistry and allied disciplines. Mini-Reviews in Medicinal Chemistry covers all areas of medicinal chemistry including developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, drug targets, and natural product research and structure-activity relationship studies. Mini-Reviews in Medicinal Chemistry is an essential journal for every medicinal and pharmaceutical chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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