有机化学 ›› 2018, Vol. 38 ›› Issue (7): 1673-1679.DOI: 10.6023/cjoc201712026 上一篇    下一篇

研究论文

6-取代-吡啶并[3,2-e] [1,2,4]三唑并[4,3-a]吡嗪类衍生物的合成及抗惊厥活性研究

李佳丽a, 胡涛a, 张洪健a, 宫国华b,c, 全哲山a   

  1. a 延边大学药学院 延吉 133002;
    b 内蒙古自治区蒙药心脑血管药理学重点实验室 通辽 028000;
    c 内蒙古民族大学附属医院 通辽 028000
  • 收稿日期:2017-12-18 修回日期:2018-02-02 出版日期:2018-07-25 发布日期:2018-04-12
  • 通讯作者: 宫国华, 全哲山 E-mail:zsquan@ybu.edu.cn;gongguohua0211@163.com
  • 基金资助:

    国家自然科学基金(Nos.21662036,81660837)资助项目.

Synthesis and Anticonvulsant Activity Evaluation of 6-Substituted-pyrido[3,2-e] [1,2,4]triazolo[4,3-a]pyrazine Derivatives

Li Jialia, Hu Taoa, Zhang Hongjiana, Gong Guohuab,c, Quan Zhe-Shana   

  1. a College of Pharmacy, Yanbian University, Yanji 133002;
    b Inner Mongolia Autonomous Region Key laboratory of Mongolian Medicine Pharmacology for Cardio-cerebral Vascular System, Tongliao 028000;
    c Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao 028000
  • Received:2017-12-18 Revised:2018-02-02 Online:2018-07-25 Published:2018-04-12
  • Contact: 10.6023/cjoc201712026 E-mail:zsquan@ybu.edu.cn;gongguohua0211@163.com
  • Supported by:

    Project supported by the National Natural Scicence Foundation of China (Nos. 21662036, 81660837).

设计合成了一系列6-取代-吡啶并[3,2-e][1,2,4]三唑并[4,3-a]吡嗪类衍生物,分别采用最大电惊厥法(MES)和旋转棒法测定其对小鼠的抗惊厥活性及神经毒性.其化学结构均经过1H NMR、13C NMR、MS和HRMS进行确征.实验结果显示,6-苯氧基-吡啶并[3,2-e][1,2,4]三唑并[4,3-a]吡嗪(5g)的半数有效剂量(ED50)为93.9 mg·kg-1,保护指数为24.3,其安全性高于对照药卡马西平,是一种潜在的抗癫痫候选化合物.

关键词: 酞吡啶并[2,3-b]吡嗪, 三唑, 合成, 抗惊厥, 最大电惊厥法

In this paper, a series of 6-substituted-pyrido[3,2-e] [1,2,4]triazolo[4,3-a]pyrazine derivatives have been synthesized. Their anticonvulsant activity and neurotoxicity in mice were evaluated by maximal electroshock (MES) and rotarod test, respectively. The structures were confirmed by 1H NMR, 13C NMR, MS and HRMS. The experimental results show that 6-phenoxypyrido[3,2-e] [1,2,4]triazolo[4,3-a]pyrazine (5g) was safer than the reference drug, carbamazepine, with ED50value of 93.9 mg·kg-1and protective index (PI) value of 24.3, which was a potential anti-epilepsy candidate compound.

Key words: pyrido[2,3-b]pyrazine, triazole, synthesis, anticonvulsant, the maximal electroshock