Design, Synthesis, and Anticonvulsant Activity Evaluation of 4-(3-Alkoxy-phenyl)-2,4-dihydro-[1,2,4]triazol-3-ones

A series of 4‐(3‐alkoxy‐phenyl)‐2,4‐dihydro‐[1,2,4]triazol‐3‐ones were synthesized using the appropriate synthetic route and evaluated experimentally in the maximal electroshock test; their neurotoxicities were evaluated by the rotarod neurotoxicity test. The structures of these compounds were confirmed by IR, MS, 1H‐NMR, and elementary analysis. All target compounds exhibited anticonvulsant activity to varying degrees in the maximal electroshock test. 4‐(3‐Benzyloxy‐phenyl)‐2,4‐dihydro‐[1,2,4]triazol‐3‐one (4i) was the most promising compound with an ED50 value of 30.5 mg/kg and a protective index (PI) of 18.63, showing a higher safety than the standard carbamazepine (PI = 6.45). In addition, the potency of compound 4i against seizures induced by pentylenetetrazole and 3‐mercaptopropionic acid suggested its broad‐spectrum activity, and the mechanisms of action including inhibition of voltage‐gated ion channels and modulation of GABAergic activity might be involved in its anticonvulsant activity. A series of 4‐(3‐alkoxy‐phenyl)‐2,4‐dihydro‐[1,2,4]triazol‐3‐ones were synthesized and evaluated by maximal electroshock test and rotarod neurotoxicity test. All target compounds exhibited anticonvulsant activity to varying degrees in the maximal electroshock test. 4‐(3‐Benzyloxy‐phenyl)‐2,4‐dihydro‐[1,2,4]triazol‐3‐one (4i) was the most promising compound with an ED50 value of 30.5 mg/kg and a protective index (PI) of 18.63, showing a higher safety than the standard carbamazepine (PI = 6.45).