等排置换及其在药物分子设计中的应用  

Bioisosteric replacement and its application in drug design

作　　者：张磊 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：《中国药物化学杂志》2014年第3期214-230,共17页Chinese Journal of Medicinal Chemistry

基　　金：国家杰出青年科学基金项目(81025017)

摘　　要：在药物分子设计中,等排置换是一种重要的局部结构改造策略。本文按改造对象的结构从简单到复杂的程度,将等排置换进行新的分类,主要包括原子或基团的等排置换、官能团的等排置换,以及环的等排置换。通过理论分析和代表性实例介绍,展示了等排置换的策略在提高化合物的活性和选择性、降低毒性和不良反应、改善药动学性质,以及增加化合物新颖性等方面的广泛应用。Bioisosteric replacement is an important and widely-used drug design strategy in the optimization process from hits to drug candidates. In this review, bioisosteric replacement is classified into atom or group replacement, functional group replacement, and ring replacement based on the complexity of the structural moieties to be replaced. The applications of bioisosteric replacement to enhance potency and selectivity, reduce toxicity and side effects, improve pharmacokinetic properties and create patent novelty are demonstrated by specific examples from recent literature.

关 键 词：等排置换 电子等排 先导化合物 药物分子设计 结构优化 

分 类 号：R91[医药卫生—药学]