有机化学 ›› 2012, Vol. 32 ›› Issue (09): 1643-1652.DOI: 10.6023/cjoc1202132 上一篇    下一篇

综述与进展

氰基在药物分子设计中的应用

王江, 柳红   

  1. 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
  • 收稿日期:2012-02-13 修回日期:2012-04-27 发布日期:2012-03-30
  • 通讯作者: 柳红 E-mail:hliu@mail.shcnc.ac.cn
  • 基金资助:

    国家杰出青年科学基金(No.81025017)资助项目

Application of Nitrile in Drug Design

Wang Jiang, Liu Hong   

  1. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203
  • Received:2012-02-13 Revised:2012-04-27 Published:2012-03-30
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No.81025017)

含氰基药物在临床治疗药物中占有相当比重.将氰基基团引入到小分子药物中是药物化学结构改造的重要研究策略之一.综述了氰基在药物分子设计中的应用,氰基的引入可以调节小分子药物的物理化学特性,改变小分子的药代动力学性质,提高药物的生物利用度;通过氢键相互作用、共价相互作用、偶极相互作用以及π-π相互作用增强配体与靶标蛋白的相互结合能力以及对其它靶标蛋白的选择性;同时,氰基是羰基、卤素等多种官能团的生物电子等排体;将氰基引入到药物小分子当中,可以通过阻断易代谢位点进而提高药物代谢稳定性等.

关键词: 氰基, 药物设计, 结构优化

Nitrile-containing compounds comprise a substantial proportion in the therapeutic drugs. It is an important strategy to introduce nitrile substitute in the small molecule for structure-based medicinal chemistry. The application of nitrile in drug design is reviewed. The nitrile can modulate the physicochemical and pharmacokinetic properties to improve bioavailability, enhance the selectivities and binding affinity to target proteins by hydrogen bond interactions, covalent interactions, polar interactions, and π-π interactions. Meanwhile, the nitrile acts as bioisostere of various functional groups such as carbonyl and halogen groups. In addition, introducing the nitrile to drug molecules can block metabolically labile sites to increase the metabolic stability of drugs.

Key words: nitrile, drug design, lead optimization