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

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

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-α]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、^(13)C 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(ED_(50))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.

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^-1 and protective index （PI） value of 24.3, which was a potential anti-epilepsy candidate compound.