Even after considerable advances in the field of epilepsy treatment, convulsions are inefficiently controlled by standard drug therapy. Herein, a series of pyrimidine-carbothioamide derivatives 4(a-t) was designed as anticonvulsant agents by doing some important structural modifications in well-known anticonvulsant drugs. Two classical animal models were used for the in vivo anticonvulsant screening, maximum electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) models; followed by motor impairment study by rotarod method. The most active compound 4g effectively suppressed seizure effect in both the animal models with median doses of 15.6 mg/kg (MES ED₅₀), 278.4 mg/kg (scPTZ ED₅₀) and 534.4 mg/kg (TD₅₀) with no sign of neurotoxicity. Furthermore, in vitro GABA-AT enzyme activity assay of 4g showed inhibitory potency (IC₅₀) of 12.23 μM. The docking study also favored the animal studies.

即使在癫痫治疗领域取得了长足的进步，抽搐仍无法通过标准药物治疗有效地控制。在此，通过对众所周知的抗惊厥药进行一些重要的结构修饰，将一系列嘧啶-碳硫酰胺衍生物4（at）设计为抗惊厥药。体内抗惊厥药物筛选采用两种经典动物模型：最大电击惊厥（MES）和皮下戊四氮（scPTZ）模型。然后通过旋转法研究运动障碍。在两种动物模型中，活性最高的化合物4g有效抑制癫痫发作的作用，中位剂量分别为15.6 mg / kg（MES ED ₅₀），278.4 mg / kg（scPTZ ED ₅₀）和534.4 mg / kg（TD ₅₀），无神经毒性迹象。此外，体外gABA-AT酶活性为4g，抑制力（IC ₅₀）为12.23μM。对接研究也支持动物研究。