A series of 4-butyl-5-(4-alkoxyphenyl)-2H-1,2,4-triazole-3(4H)-ones (6a-6u) were designed and synthesized. The anticonvulsant effects and neurotoxicity of the compounds were evaluated with maximal electroshock test and rotarod test. Among the synthetic compounds, 4-butyl-5-(4-(2-fluorinebenzyl)phenyl)-2H-1,2,4-triazole-3 (4H)-one (6k) was the most potent with ED50 value of 27.4 mg/kg and protect index (PI = TD50/ED50) value of 12.0. Besides the anti-MES efficacy, the potency of compound 6k against seizures induced by pentylenetetrazole (PTZ), 3-mercaptopropionic acid (3-MP), and bicuculline (BIC) were also established, which suggested that the mechanisms of action including enhancing of GABAergic activity might be involved in its anticonvulsant activity.
Anticonvulsant, GABA, Maximal electroshock test, Neurotoxicity, Synthesis, Triazolone