The voltage-gated sodium (Na_v) channel is one of most important targets for treatment of epilepsy, and rufinamide is an approved third-generation anti-seizure drug as Na_v1.1 channel blocker. Herein, by triazenylation of rufinamide, we reported the triazenyl triazoles as new Na_v1.1 channel blocker for treatment of epilepsy. Through the electrophysiological activity assay, compound 6a and 6e were found to modulate the inactivation voltage of Na_v 1.1 channel with shift of −10.07 mv and −11.28 mV, respectively. In the pentylenetetrazole (PTZ) mouse model, 6a and 6e reduced the seizure level, prolonged seizure latency and improved the survival rate of epileptic mice at an intragastric administration of 50 mg/kg dosage. In addition, 6a also exhibited promising effectiveness in the maximal electroshock (MES) mouse model and possessed moderate pharmacokinetic profiles. These results demonstrated that 6a was a novel Na_v1.1 channel blocker for treatment of epilepsy.

电压门控钠（Na _{v ）通道是治疗癫痫最重要的靶点之一，而卢非胺作为 Na v} 1.1 通道阻滞剂是获批的第三代抗癫痫药物。在此，通过rufinamide 的三氮烯基化，我们报道了三氮烯基三唑类作为治疗癫痫的新型Na _{v 1.1 通道阻滞剂。}通过电生理活性测定，发现化合物6a和6e分别调节Na _v 1.1通道的失活电压，位移分别为-10.07 mv和-11.28 mV。在戊四唑 (PTZ) 小鼠模型中，6a和6e以 50 mg/kg 的剂量灌胃降低癫痫发作水平，延长癫痫发作潜伏期并提高癫痫小鼠的存活率。此外，6a在最大电休克 (MES) 小鼠模型中也表现出有希望的有效性，并具有中等的药代动力学特征。这些结果表明，6a是一种用于治疗癫痫的新型 Na _{v 1.1 通道阻滞剂。}