Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Egypt.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Menoufia University, Egypt.
Bioorg Chem. 2020 Aug;101:104020. doi: 10.1016/j.bioorg.2020.104020. Epub 2020 Jun 17.
New imidazolidindiones and tetra-substituted imidazole derivatives were designed, synthesized, and evaluated for the anticonvulsant activity through pentylenetetrazole (PTZ)-induced seizures and maximal electroshock (MES) tests using valproate sodium and phenytoin sodium as reference drugs, respectively. Most of the target compounds showed excellent activity against pentylenetetrazole (PTZ)-induced seizures with fair to no-activity against MES. Compounds 3d, 4e, 11b, and 11e showed higher activity (120%) than that of valproate sodium in PTZ model. Almost all compounds showed no neurotoxicity, as indicated by the rotarod test. Estimation of physicochemical properties and pharmacokinetic profiles of the target compounds were studied. The chemical structures of the target compounds were characterized by different spectrometric methods and elemental analysis.
新型咪唑并[1,5-a]嘧啶酮和四取代咪唑衍生物被设计、合成，并通过戊四氮（PTZ）诱导的癫痫发作和最大电休克（MES）试验进行评估，分别以丙戊酸钠和苯妥英钠作为参考药物。大多数目标化合物对戊四氮（PTZ）诱导的癫痫发作具有优异的活性，对 MES 无活性或活性较低。化合物 3d、4e、11b 和 11e 在 PTZ 模型中的活性（120%）高于丙戊酸钠。几乎所有化合物在旋转棒试验中均无神经毒性。目标化合物的物理化学性质和药代动力学特征的估算也进行了研究。目标化合物的化学结构通过不同的光谱方法和元素分析进行了表征。
