多样性合成及其在药物发现中的应用  

Diversity-oriented synthesis and its application in drug discovery

作　　者：张磊 郑明月 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》2015年第4期419-433,共15页Acta Pharmaceutica Sinica

基　　金：国家杰出青年科学基金项目(81025017)

摘　　要：多样性合成旨在高效地构建取代基、官能团、立体化学和骨架多样的化合物库,进而发现多样性的生物学效应。本文结合代表性实例,总结了多样性合成的常见策略,包括基于试剂的策略、基于底物的策略、"构建-耦合-配对"策略以及基于优势结构的多样性合成策略。同时,介绍了通过多样性合成构建的化合物库在药物发现中的应用。Diversity-oriented synthesis（DOS） aims to efficiently generate collections of small molecules with diverse appendages, functional groups, stereochemistry and skeletons, thus yielding diverse biological activities capable of modulating a wide variety of biological processes. In this review, we discussed the common strategies employed in DOS with specific examples from recent literature, including reagent-based approach, substrate-based approach, build-couple-pair strategy and privileged substructure-based DOS. The application of some DOS libraries in drug discovery is also presented.

关 键 词：多样性合成 多样性 化学空间 化合物库 药物发现 

分 类 号：R916[医药卫生—药学]