期刊论文

中文

中国药物化学杂志

1005-0108

2013

23

4

277-285

10.14142/j.cnki.cn21-1313/r.2013.04.009

The research was supported by the Special Fund for Basic Scientific Research of Central Colleges, South-Central University for Nationalities（CZY11004） and in part by the National Institutes of Health （ RCI MH088480）, Natural Science Foundation （ CHE-1111761 ）, National Natural Science Foundation of China（20602014,20503008,20372023,21273089）

本校为其他机构

目的 设计和合成了6个2-取代-9-苄基-嘌呤-6-酮衍生物并测试了其对磷酸二酯酶-2的抑制活性,进而研究PDE2酶对该类抑制剂的作用方式.方法 以2-氨基-2-氰基乙酰胺为原料先合成5-氨基-4-羰酰胺咪唑类衍生物,接着用微波辅助的方法合成了目标化合物.结果与结论 微波辅助的方法大大缩短反应时间,从传统的加热回流20h缩短到目前的30 min.抑制活性结果表明,化合物2b[9-苄基-2-(3,4-二甲氧基苄基)-1,9-二氢嘌呤-6-酮]有非常明显的抑制活性(IC50=1.35 μmol·L-1).配体和蛋白质对接的结果分析表明,嘌呤-6-酮衍生物同磷酸二酯酶-2的催化区域的结合主要通过氢键和π-π堆积作用实现的.

A novel approach to synthesize six purin-6-one derivatives in microwave hradiation conditions was reported in this study. The reaction time was dramatically reduced to 30 rain. Inhibitory activity tests against phosphodiesterase-2 （ PDE2 ） show that compound 2b （ 9-benzyl-2- （3,4-dimethoxy-benzyl） -1,9-dihydro-pu- rin-6-one） exhibits a significant inhibitory effect with an IC50 value of 1.35 μmol. L-1. The results from lig- and-protein docking and analysis reveal that these purin-6-one derivatives interact with the PDE2 cataly...