药学学报, 2018, 53(2): 192-201
引用本文:
吴小伟, 王江, 柳红. 先导化合物结构优化策略(六)——改善化合物血浆稳定性[J]. 药学学报, 2018, 53(2): 192-201.
WU Xiao-wei, WANG Jiang, LIU Hong. Lead compound optimization strategy (6)-improving the plasma stability[J]. Acta Pharmaceutica Sinica, 2018, 53(2): 192-201.

先导化合物结构优化策略(六)——改善化合物血浆稳定性
吴小伟, 王江, 柳红
中国科学院上海药物研究所, 新药研究国家重点实验室, 上海 201203
摘要:
血浆稳定性是影响先导化合物成药性的关键因素。通过化学结构修饰方法提高化合物的血浆稳定性有助于改善化合物在体内的药动学和药效学性质。本文综述了通过化学结构修饰改善化合物血浆稳定性的基本策略,包括:生物电子等排、增加空间位阻、成环修饰以及骨架跃迁等。
关键词:    血浆稳定性      结构修饰      先导化合物      生物电子等排     
Lead compound optimization strategy (6)-improving the plasma stability
WU Xiao-wei, WANG Jiang, LIU Hong
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Abstract:
Plasma stability plays an important role in the druggability of lead compound. Improving the plasma stability of compounds by structural modification can lead to good pharmacokinetic and pharmacodynamics properties. This review provides a summary of varieties of structure modification strategies for improving plasma stability including bioisosterism, increasing steric hindrance, ring closure, scaffold hopping and etc.
Key words:    plasma stability    structural modification    lead compound    bioisosterism   
收稿日期: 2017-09-20
DOI: 10.16438/j.0513-4870.2017-0934
基金项目: 国家杰出青年科学基金资助项目(81025017).
通讯作者: 柳红,Tel/Fax:86-21-50807042,E-mail:hliu@simm.ac.cn
Email: hliu@simm.ac.cn
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