先导化合物结构优化策略(三)——通过化学修饰改善水溶性  

Lead compound optimization strategy(3)——structure modification strategies for improving water solubility

作　　者：栗增 王江 周宇 柳红 

机构地区：[1]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

出　　处：《药学学报》2014年第9期1238-1247,共10页Acta Pharmaceutica Sinica

基　　金：国家杰出青年科学基金资助项目(81025017)

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。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.

关 键 词：水溶性 结构修饰 前药 先导化合物优化 

分 类 号：R916[医药卫生—药学]