10-_三_通过化学修饰改善水溶性_栗增.pdfVIP

· 1238 · 药学学报 Acta Pharmaceutica Sinica 2014, 49 (9): 1238?1247 先导化合物结构优化策略 (三) —— 通过化学修饰改善水溶性 栗 增, 王 江, 周 宇, 柳 红* (中国科学院上海药物研究所, 受体结构与功能重点实验室, 上海 201203) 摘要: 水溶性是有机小分子药物极为重要的物理化学性质, 也是小分子药物研发过程中的关键问题之一。良 好的水溶性有助于药效的发挥和药代动力学性质的改善。在药物化学领域, 通过化学结构修饰方法改善药物的 水溶性, 是从溶解的本质上考虑和解决问题的基本方法。本文综述了通过化学结构修饰改善水溶性的基本策略, 包括成盐修饰、引入极性基团、降低脂溶性、构象优化、前药修饰等。 关键词: 水溶性; 结构修饰; 前药; 先导化合物优化 中图分类号: R916 文献标识码: A 文章编号: 0513-4870 (2014) 09-1238-10 Lead compound optimization strategy (3) — structure modification strategies for improving water solubility LI Zeng, WANG Jiang, ZHOU Yu, LIU Hong* (Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China) Abstract: Water solubility is an essential physical chemistry property of organic small molecule drug and is also a very important issue in drug discovery. Good water solubility often leads to a good drug potency and pleasant pharmacokinetic profiles. To improve water solubility, structure modification is a straight and effective way based on the theory of water solubility. This review summarized valid structure modification strategies for improving water solubility including salt formation, polar group introduction, liposolubility reduction, conformation optimization and prodrug. Key words: water solubility; structure modification; prodrug; lead optimization ?先导化合物的发现及结构优化是创新药物研究 化学修饰改善先导化合物水溶性的理论基础和基本 成败的核心问题之一