BACKGROUND AND OBJECTIVE Phthalimide, as the rigid form of ameltolide, exhibits a phenytoin-like profile of drug-receptor interaction and is active in the MES model and inactive in the PTZ model as an anti-epileptic agent. In this research, based on the isosteric replacement, we reported the design, preparation, and antiepileptic activity of 13 new analogs of pyrrolopyridine and isoindole. METHODS The designed compounds were prepared by condensing 3, 4-pyridine dicarboxylic anhydride, or 4-fluorophthalic anhydride with different aryl amines. MES and PTZ-induced seizure models were utilized to evaluate the antiepileptic effect of the prepared ligands. RESULTS It was found that the prepared ligands have significantly affected both tonic and clonic seizures. In tonic seizures, the prepared compounds decreased mortality to a significant extent, and in clonic seizures, they significantly showed better frequency and latency. Compounds 9, 12, and 13 were the most potent ligands than phenytoin. CONCLUSION It is concluded that the best distance between two aryl parts is two bonds, and the substitution of the nitro group at the meta position of the phenyl ring is better than the para position. Our research group has investigated this concept for designing newer compounds with better anticonvulsant activity.

中文翻译：

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吡咯并吡啶和异吲哚作为潜在的抗惊厥剂：设计、合成和药理学评价。

背景和目的 邻苯二甲酰亚胺作为阿美托内酯的刚性形式，具有苯妥英样的药物-受体相互作用特征，在MES模型中具有活性，在PTZ模型中作为抗癫痫剂无活性。在这项研究中，基于等排替代，我们报道了 13 种新型吡咯并吡啶和异吲哚类似物的设计、制备和抗癫痫活性。方法 设计的化合物由3, 4-吡啶二羧酸酐或4-氟邻苯二甲酸酐与不同的芳基胺缩合制备。利用 MES 和 PTZ 诱导的癫痫模型来评估制备的配体的抗癫痫作用。结果发现制备的配体对强直性和阵挛性癫痫发作均有显着影响。在强直性癫痫发作中，制备的化合物在很大程度上降低了死亡率，在阵挛性癫痫发作中，他们显着表现出更好的频率和潜伏期。化合物 9、12 和 13 是比苯妥英最有效的配体。结论 得出的结论是两个芳基部分之间的最佳距离是两个键，并且苯环间位的硝基取代比对位要好。我们的研究小组研究了这一概念，以设计具有更好抗惊厥活性的新型化合物。