多靶点配体与药物设计.pdf

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2005 年第 29 卷第 8 期第 337 页·综述与专论·
药学进展
Progress in Pharmaceutical Sciences 2005 , Vol. 29 , No. 8 337
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综述与专论
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多靶点配体与药物设计
陈翠丽, 尤启冬, 李志裕
(中国药科大学药化教研室,江苏南京 210009)
[摘要] 综述有关多靶点配体药物设计的基本原理和方法,包括整合共有药效团法、轭合药效团法、可分解轭合
药效团法及筛选法;并讨论多靶点配体与合理药物设计的关系以及设计中应注意的问题,为新药的研究与开发提
供参考。
[关键词] 多靶点配体;合理药物设计;药效团;整合;轭合物;筛选
[中图分类号] R914. 2 [文献标识码] A [文章编号3 ] 1001 - 5094(2005) 08 - 0337 - 07
The Multiple Ligands and Drug De sign
CHEN Cui li , YOU Qi dong , LI Zhi yu
( Department of Medicinal Chemistry , China Pharmaceutical University , Nanjing 210009 , China)
[ Abstract] The basic principle and methodology of design for new drug with multiple ligands reported in re
cent years were reviewed , including overlapping pharmacophores ,conjugated pharmacophores , cleavable conju
gates and screening. The relationship between multiple ligands and rational drug design and the issues worthy
of note in design for new drug with multiple ligands were discussed. These would be helpful for the research
and development of new drug
[ Key words] Multiple ligands ; Rational drug design ; Pharmacophore ; Overlapping ; Conjugate ; Screening
新药的研究设计经历了 3 个阶段的演化:非选功效和降低毒副作用方面达到较佳效果,与之相比,
择性药物→选择性药物→多靶点配体药物。如抗抑药物通过多靶点调节则可产生更佳治疗效果及更少
郁药的发展从非选择性三环类药物(如阿米替林) , 副作用。因此,提出了“多靶点配体药物”设计理念,
到选择性 5 羟色胺(5 HT) 转运蛋白(SERT) 抑制剂即通过综合分析,合理设计出具选择性的配体结构
(如氟