The research involves the synthesis of a series of new pyridine analogs 5(i‐x) and their evaluation for anti‐epileptic potential using in silico and in vivo models. Synthesis of the compounds was accomplished by using the Vilsmeier‐Haack reaction principle. AutoDock 4.2 was used for their in silico screening against AMPA (‐amino‐3‐hydroxy‐5‐methylisoxazole) receptor (PDB ID:3m3f). For in vivo testing, the maximal electroshock seizure (MES) model was used. The physicochemical, pharmacokinetic, drug‐like, and drug‐score features of all synthesized compounds were assessed using the online Swiss ADME and Protein Plus software. The in silico results showed that all the synthesized compounds 5(i‐x) had 1–3 interactions and affinities ranging from −6.5 to −8.0 kJ/mol with the targeted receptor compared to the binding affinities of the standard drug phenytoin and the original ligand of the target (P99), which were −7.6 and −6.8 kJ/mol, respectively. In vivo study results showed that the compound 5‐Carbamoyl‐2‐formyl‐1‐[2‐(4‐nitrophenyl)‐2‐oxo‐ethyl]‐pyridinium gave 60% protection against epileptic seizures compared to 59% protection afforded by regular phenytoin. All of them met Lipinski's rule of five and had drug‐likeness and drug score values of 0.55 and 0.8, respectively, making them chemically and functionally like phenytoin. According to the findings of the studies, the synthesized derivatives have the potential to be employed as a stepping stone in the development of novel anti‐epileptic drugs.

中文翻译：

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作为针对 AMPA（α-氨基-3-羟基-5-甲基异恶唑）受体的抗癫痫药的新型吡啶同系物的合成、计算机筛选和生物学评价

该研究涉及一系列新型吡啶类似物 5(i-x) 的合成，并使用计算机和体内模型评估其抗癫痫潜力。该化合物的合成是利用 Vilsmeier-Haack 反应原理完成的。AutoDock 4.2 用于他们的计算机模拟针对 AMPA（-氨基-3-羟基-5-甲基异恶唑）受体（PDB ID：3m3f）的筛查。对于体内测试，使用最大电击癫痫发作（MES）模型。使用在线 Swiss ADME 和 Protein Plus 软件评估所有合成化合物的理化、药代动力学、类药和药物评分特征。这计算机模拟结果表明，与标准药物苯妥英和原始配体的结合亲和力相比，所有合成的化合物 5(i-x) 与目标受体具有 1-3 个相互作用和亲和力，范围为 -6.5 至 -8.0 kJ/mol目标（P99），分别为-7.6和-6.8 kJ/mol。体内研究结果表明，化合物 5-氨基甲酰基-2-甲酰基-1-[2-(4-硝基苯基)-2-氧代-乙基]-吡啶鎓对癫痫发作具有 60% 的保护作用，而常规药物则可提供 59% 的保护作用。苯妥英。它们均符合 Lipinski 的五法则，药物相似度和药物评分值分别为 0.55 和 0.8，这使得它们在化学和功能上类似于苯妥英。根据研究结果，合成的衍生物有潜力成为新型抗癫痫药物开发的垫脚石。