药学学报, 2013, 48(10): 1521-1531
王江, 柳红. 先导化合物结构优化策略(一)——改变代谢途径提高代谢稳定性[J]. 药学学报, 2013, 48(10): 1521-1531.
WANG Jiang, LIU Hong. Lead compound optimization strategy (1)——changing metabolic pathways and optimizing metabolism stability[J]. Acta Pharmaceutica Sinica, 2013, 48(10): 1521-1531.

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
先导化合物结构优化是新药研发的关键环节。通过改变先导化合物的代谢途径可以改善化合物的药代动力学特性, 延长药物在体内的作用时间, 增强代谢稳定性, 提高生物利用度。本文主要综述了通过改变代谢途径提高代谢稳定性的先导化合物结构优化策略, 包括封闭代谢位点、降低脂溶性、骨架修饰、生物电子等排以及前药等。
关键词:    代谢稳定性      先导化合物      封闭代谢位点      脂溶性      半衰期     
Lead compound optimization strategy (1)——changing metabolic pathways and optimizing metabolism stability
WANG Jiang, LIU Hong
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Lead compound optimization plays an important role in new drug discovery and development. The strategies for changing metabolic pathways can modulate pharmacokinetic properties, prolong the half life, improve metabolism stability and bioavailability of lead compounds. The strategies for changing metabolic pathways and improving metabolism stability are reviewed. These methods include blocking metabolic site, reduing lipophilicity, changing ring size, bioisosterism, and prodrug.
Key words:    metabolism stability    lead compound    block metabolic site    lipophilicity    half life   
收稿日期: 2013-05-10
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@mail.shcnc.ac.cn
Email: hliu@mail.shcnc.ac.cn
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