高等学校化学学报 ›› 2017, Vol. 38 ›› Issue (3): 392-397.doi: 10.7503/cjcu20160880

• 有机化学 • 上一篇    下一篇

4-N-苯胺基喹啉衍生物的合成及胆碱酯酶抑制活性

刘玉明(), 田丽珺, 胡栋, 聂建兵   

  1. 天津理工大学化学化工学院, 天津 300384
  • 收稿日期:2016-12-06 出版日期:2017-03-10 发布日期:2017-02-23
  • 作者简介:联系人简介: 刘玉明, 男, 博士, 副教授, 主要从事药物化学和天然药物化学研究. E-mail: liuyuming@tjut.edu.cn
  • 基金资助:
    国家自然科学基金(批准号: 81073153)资助.

yntheses and Anti-cholinesterase Activity of 4-N-Phenylaminoquinoline Derivatives

LIU Yuming*(), TIAN Lijun, HU Dong, NIE Jianbing   

  1. School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, China
  • Received:2016-12-06 Online:2017-03-10 Published:2017-02-23
  • Contact: LIU Yuming E-mail:liuyuming@tjut.edu.cn
  • Supported by:
    † Supported by the National Natural Science Foundation of China(No.81073153).

摘要:

设计合成了一系列4-N-苯胺基喹啉类衍生物, 采用Ellman法测定了目标化合物对乙酰胆碱酯酶(AChE)和丁酰胆碱酯酶(BChE)的抑制活性. 结果表明, 当喹啉环上连有伸长的吡啶季铵盐片段时, 可显著提高目标化合物的胆碱酯酶抑制作用. 化合物16对AChE和BChE具有明显的双重抑制作用, 其IC50值分别为0.92和14.20 μmol/L, 抑制效果强于阳性对照药加兰他敏.

关键词: 4-N-苯胺基喹啉类衍生物, 胆碱酯酶抑制活性, 构效关系

Abstract:

A series of 4-N-Phenylaminoquinoline derivatives was designed and synthesized, and their anti-cholinesterase activities were evaluated using Ellman assay. The results demonstrated that the stretched-out quaternary pyridine in quinoline ring greatly improved the cholinesterase inhibition of target compounds. Compound 16 exhibited the most potent inhibitory activities against both acetylcholinesterase(AChE) and butyrylcholinesterase(BChE) from the prepared series, with IC50 values of 0.92 and 14.20 μmol/L, respectively, which showed superior activitities compared with the reference drug galanthamine. These results suggest that compound 16 may be valuable as a new parent compound for further structural modifications.

Key words: 4-N-Phenylaminoquinoline derivatives, Anti-cholinesterase activity, Structure-activity relationship(Ed.: P, H, F, K)

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