BACKGROUND Epilepsy is a serious and common neurological disorder threatening the health of humans. Despite enormous progress in epileptic research, the anti-epileptic drugs present many limitations. These limitations prompted the development of more safer and effective AEDs. METHODS A series of N-substituted (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)- 2-thioxothiazolidin-4- one derivatives and 5-substituted-thioxothiazolidindione derivatives were designed, synthesized and tested for anticonvulsant activity against maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ). Neurotoxicity was determined by the rotarod test. RESULTS Among them, the most potent 4e displayed high protection against MES-induced seizures with an ED50 value of 9.7 mg/kg and TD50 value of 263.3 mg/kg, which provided 4e with a high protective index (TD50/ED50) of 27.1 comparable to reference antiepileptic drugs. 4e clearly inhibits the NaV1.1 channel in vitro. The molecular docking study was conducted to exploit the results. CONCLUSION Stiripentol is a good lead compound for further structural modification. Compound 4e was synthesized, which displayed remarkable anticonvulsant activities, and the NaV1.1 channel inhibition was involved in the mechanism of action of 4e.

中文翻译：

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N-取代的（Z）-5-（苯并[d] [1,3]二恶酚-5-基亚甲基）-2-噻吩并恶唑烷丁-4-酮衍生物和5-取代的噻吩并恶唑烷二酮衍生物作为强抗惊厥剂的合成和评价。

背景技术癫痫病是威胁人类健康的严重且常见的神经系统疾病。尽管在癫痫研究中取得了巨大进展，但是抗癫痫药仍存在许多局限性。这些局限性促使人们开发出更加安全有效的AED。方法设计，合成和合成了一系列的N-取代的（Z）-5-（苯并[d] [1,3]二恶酚-5-基亚甲基）-2-硫代噻唑啉酮-4-一衍生物和5-取代的硫代噻唑啉酮二酮衍生物。测试了针对最大电击（MES）和皮下戊四氮（scPTZ）的抗惊厥活性。神经毒性通过旋转试验来确定。结果其中，最有效的4e对MES诱发的癫痫发作具有高度保护作用，ED50值为9.7 mg / kg，TD50值为263.3 mg / kg，与参考抗癫痫药物相比，该产品为4e提供了27.1的高保护指数（TD50 / ED50）。4e在体外明显抑制NaV1.1通道。进行了分子对接研究以利用结果。结论Stiripentol是用于进一步结构修饰的良好先导化合物。合成的化合物4e具有显着的抗惊厥活性，而NaV1.1通道的抑制作用参与了4e的作用机理。