Chin. J. Org. Chem. ›› 2012, Vol. 32 ›› Issue (02): 413-419 .DOI: 10.6023/cjoc1105143 Previous Articles     Next Articles


新型他克林-吲哚杂二联体的微波促进Husigen [3+2]环加成反应合成及生物活性

郭永彪, 刘海波, 许明   

  1. 防化研究院 北京 102205
  • 收稿日期:2011-05-14 修回日期:2011-10-09 发布日期:2012-03-09
  • 通讯作者: 许明;

Synthesis and Bioactivity of Novel Tacrine-Indole Hybrids by Microwave-Assisted Huisgen [3+2] Cycloaddition Reaction

Guo Yongbiao, Liu Haibo, Xu Ming   

  1. Research Institute of Chemical Defense, Beijing 102205
  • Received:2011-05-14 Revised:2011-10-09 Published:2012-03-09

3-(Propargyl-propionamine)indole (4a) and 3-(propargyl-butyramide)indole (4b) were prepared from indole-3-propionic acid (3a) and indole-3-butyric acid (3b) by condensation with propargylamine, respectively. Twelve novel acetylcholinesterase inhibitors, tacrine-indole hybrids, were synthesized from 4a, 4b and 9-(azido-ethyl-amino)- 1,2,3,4-tetrahydroacridine derivatives (5a5c) by microwave-assisted Huisgen [3+2] cycloaddition reaction. These novel compounds were determined by NMR, IR and HRMS techniques. The preliminary bioassay showed that all of them exhibited better AChE (electrophorus) inhibitory activity. Particularly, the IC50 values of compounds 2b and 2d were 1.6 and 2.0 nmol· L-1 respectively, which were 6.9 and 5.5 times respectively more potent than N-[6-(6-chloro-1,2,3,4-tetrahydroacridin-9- yl-amino)hexyl]-3-(1H-Indol-3-yl)propionamide (6T6BA) (IC50=11.0 nmol·L-1, electrophorus).

Key words: tacrine-indole hybrids, Huisgen [3+2] cycloaddition, acetylcholinesterase inhibitors, microwave