A series of 5‐substituted benzo[d][1,3]dioxole derivatives was designed, synthesized, and tested for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens. Neurotoxicity was determined by rotarod test. In the preliminary screening, six compounds, 3a, 3c, 3d, and 4d–f, showed promising anticonvulsant activities in the MES model, and compounds 4c and 4d exhibited full protection against seizures at doses of 300 mg/kg in the scPTZ model. Among the synthesized compounds, 3c as the most active compound showed high protection against the MES‐induced seizures with an ED50 value of 9.8 mg/kg and a TD50 value of 229.4 mg/kg after intraperitoneal injection into mice, thus providing compound 3c with a high protective index (TD50/ED50) of 23.4 comparable to those of reference antiepileptic drugs.

中文翻译：

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5-取代苯并[d][1,3]二氧杂环戊烯衍生物作为强效抗惊厥药的设计与合成

使用最大电休克 (MES) 和皮下戊四唑 (scPTZ) 屏幕设计、合成和测试了一系列 5-取代苯并[d][1,3] 二氧杂环戊二烯衍生物的抗惊厥活性。通过旋转棒试验确定神经毒性。在初步筛选中，6 种化合物 3a、3c、3d 和 4d-f 在 MES 模型中显示出有希望的抗惊厥活性，化合物 4c 和 4d 在 scPTZ 模型中以 300 mg/kg 的剂量显示出对癫痫发作的完全保护。在合成的化合物中，3c作为最活跃的化合物对MES诱导的癫痫发作具有高度的保护作用，腹腔注射小鼠后的ED50值为9.8 mg/kg，TD50值为229.4 mg/kg，从而为化合物3c提供了23.4 的高保护指数 (TD50/ED50) 与参考抗癫痫药物相当。