文献类型：期刊文献

中文题名：上市药物与中止药物理化性质差异探讨

英文题名：Comparison study of difference in physicochemical properties between approved and discontinued drugs

作者：倪炜[1];郑新羽[1];王熳炯[1];毛斐[1];李剑[1]

机构：[1]华东理工大学药学院,上海200237

年份：2018

卷号：28

期号：6

起止页码：494

中文期刊名：中国药物化学杂志

外文期刊名：Chinese Journal of Medicinal Chemistry

收录：CSTPCD;;北大核心:【北大核心2017】；CSCD:【CSCD_E2017_2018】；

基金：国家自然科学基金项目(21702061)

语种：中文

中文关键词：类药性质;理化性质;成药性;中止药物

外文关键词：drug-likeness;physicochemical property;druggability;discontinued drug

摘要：目的探讨上市及中止药物关键理化性质的相同与差异规律,用于指导药物研发工作者在新药开发早期阶段设计更易于成药的化合物,减少新药研发失败率,推动新药研发进程。方法基于上市及中止药物数据库药物的化学结构,对比分析上市及中止药物分子量(Mr)、脂水分布系数(log P)、解离常数(p Ka)、重原子比例(R)等关键理化性质的相同与差异。结果与结论与中止药物相比,上市药物的Mr整体分布在较低的Mr区间,表明Mr小的候选药物发展成为上市药物的几率更高;在log P大于3的各单个区间内,中止全集和口服药物所占比例全部高于上市药物,表明当候选药物log P大于3时,其研发失败几率增大;上市中枢神经系统(CNS)药物的log P分布与中止CNS药物的相差不大,表明CNS药物研发中,log P不再是目前药物研发失败的主要因素;上市药物和中止药物的p Ka和重原子比例分布相差不大,表明p Ka和重原子比例不是目前药物研发失败的主要因素。
Drug efficacy and safety, the two indispensable essential factors of drugs,are the most important reasons of the failure of clinical drugs. Molecular weight,lipo-hydro partition coefficient,dissociation constant and the heavy atoms proportion are important physicochemical properties of organic small molecule drug and are also very important indicators in evaluating the druggability of small molecule candidate drugs. The rules obtained by comparing the physicochemical properties of listed and discontinued drugs could guide medicinal chemists to design compounds with better druggability in the early stages of new drug research and development, reducing the failure rate of drug research and development and promoting the process of new drug development. Based on the chemical structure of listed and discontinued drugs, this text focused on exploring the similarities and differences of physicochemical properties of the listed and discontinued drugs by comparatively analyzing their distribution.