A series of (E)-3-(benzo[d][1,3]dioxol-5-ylmethylene)pyrrolidin-2-one derivatives were designed, synthesized, and evaluated for their anticonvulsant activities. In the preliminary screening, compounds 5, 6a–6f and 6h–6i showed promising anticonvulsant activities in MES model, while 6f and 6g represented protection against seizures at doses of 100 mg/kg and 0.5 h in scPTZ model. The most active compound 6d had a high-degree protection against the MES-induced seizures with ED₅₀ value of 4.3 mg/kg and TD₅₀ value of 160.9 mg/kg after intraperitoneal (i.p.) injection in mice, which provided 6d in a high protective index (TD₅₀/ED₅₀) of 37.4 comparable to the reference drugs. Beyond that, 6d has been selected and evaluated in vitro experiment to estimate the activation impact. Apparently, 6d clearly inhibits the Na_v1.1 channel. Our preliminary results provide new insights for the development of small-molecule activators targeting specifically Na_v1.1 channels to design potential drugs for treating epilepsy. The computational parameters, such as homology modeling, docking study, and ADME prediction, were made to exploit the results.

设计，合成，合成了一系列（E）-3-（苯并[ d ] [1,3]二恶唑-5-基亚甲基）吡咯烷-2-酮衍生物，并评价了它们的抗惊厥活性。在初步筛选中，化合物5，图6a - 6f的和6H - 6I显示在MES模型有前途的抗惊厥活性，而1207和6克表示的剂量的100mg / kg的保护，防止癫痫发作和在scPTZ模型0.5小时。活性最高的化合物6d对MES引起的癫痫发作具有高度保护作用，ED ₅₀值为4.3 mg / kg，TD ₅₀小鼠腹膜内注射后ip值为160.9 mg / kg ，可提供6d的高保护指数（TD ₅₀ / ED ₅₀），相当于参考药物的37.4。除此之外，还选择了6d并进行了体外实验评估，以评估其活化影响。显然，6d明显抑制了Na _v 1.1通道。我们的初步结果为开发专门针对Na _v的小分子活化剂提供了新见识。1.1设计潜在药物治疗癫痫的途径。计算参数，如同源性建模，对接研究和ADME预测，都可以利用这些结果。