A series of 7-alkoxy - [1,2,4] triazolo [1, 5-a] pyrimidine derivatives were designed and synthesized. Maximal electroshock (MES) and pentylenetetrazole (PTZ) tests were utilized to access their anticonvulsant activity. Most of the series of compounds exhibited significant anti-seizure effects. Further studies demonstrated that the anticonvulsant activity of these compounds mainly depended on their allosteric potentiation of GABA_A receptors. Among them, compound 10c was picked for the mechanism study due to its potent activity. The compound is more sensitive to subunit configurations of synaptic α1β2γ2 and extrasynaptic α4β3δ GABA_A receptors, but there were no effects on NMDA receptors and Nav1.2 sodium channels. Meanwhile, 10c acted on the sites of GABA_A receptors distinct from commonly used anticonvulsants benzodiazepines and barbiturates. Furthermore, studies from native neurons demonstrated that compound 10c also potentiated the activity of native GABA_A receptors and reduced action potential firings in cultured cortical neurons. Such structural compounds may lay a foundation for further designing novel antiepileptic molecules.

设计合成了一系列7-烷氧基-[1,2,4]三唑并[1,5-a]嘧啶衍生物。最大电击 (MES) 和戊四唑 (PTZ) 测试用于评估其抗惊厥活性。该系列化合物中的大多数都表现出显着的抗癫痫作用。进一步的研究表明，这些化合物的抗惊厥活性主要取决于它们对 GABA _A受体的变构增强作用。其中，化合物10c因其强大的活性而被选中进行机理研究。_{该化合物对突触 α1β2γ2 和突触外 α4β3δ GABA A}受体的亚基构型更敏感，但对 NMDA 受体和 Nav1.2 钠通道没有影响。同时，10c作用于不同于常用抗惊厥药苯二氮卓类和巴比妥类药物的 GABA _{A受体位点。}此外，对天然神经元的研究表明，化合物10c还增强了天然 GABA _A受体的活性，并降低了培养的皮层神经元的动作电位放电。这种结构化合物可能为进一步设计新型抗癫痫分子奠定基础。