有机化学 ›› 2011, Vol. 31 ›› Issue (09): 1445-1451. 上一篇    下一篇

研究论文

益母草碱类似物设计、合成及其Na/H交换器-1抑制活性

钟国琛1,彭家志1,李家明*,1,徐云根2,周鹏1,盛日正1   

  1. (1安徽中医学院药学院 安徽省现代中药重点实验室 合肥 230031)
    (2中国药科大学药物化学教研室 南京 210009)
  • 收稿日期:2011-01-07 修回日期:2011-03-31 出版日期:2011-09-25 发布日期:2011-04-27
  • 通讯作者: 李家明 E-mail:lijiaming2004@sina.com

Design, Synthesis and Sodium Hydrogen Exchanger Isoform-1 (NHE-1) Inhibitory Activity of Leonurine Analogues

Zhong Guochen1 Peng Jiazhi1 Li Jiaming*,1 Xu Yungen2 Zhou Peng1 Sheng Rizheng1   

  1. (1 Anhui Key Laboratory of Traditional Chinese Medicine, Department of Pharmacy, Anhui College of Traditional Chinese Medicine, Hefei 230031)
    (2 Department of Medicinal Chem-istry, China Pharmaceutical University, Nanjing 210009)
  • Received:2011-01-07 Revised:2011-03-31 Online:2011-09-25 Published:2011-04-27

以中药益母草中有效成分益母草碱为先导化合物, 按生物电子等排原理, 设计合成了18个益母草碱类似物. 通过MS, 1H NMR, 13C NMR对化合物结构进行表征. 初步的药效研究结果表明部分化合物具有Na/H交换器-1 (NHE-1)抑制活性, 其中化合物1a1e的活性显著强于阳性对照药Cariporide.

关键词: 益母草碱, NHE-1抑制剂, 心肌保护, 合成<

Leonurine, a useful compound of Chinese traditional medicine, was used as leading compounds. Eighteen leonurine analogues were designed and synthesized based on the bioisosterism. Their structures were characterized by 1H NMR, 13C NMR and mass spectra. The results of preliminary pharmacological tests showed that some of compounds possess sodium hydrogen exchanger isoform-1 (NHE-1) inhibitory effects, among them, the inhibitory activities of compounds 1a and 1e were stronger than cariporide.

Key words: leonurine, ischemia-reperfusion injury, NHE-1 inhibitory activity, synthesis