Synthesis and Evaluation of the Anticonvulsant Activities of Triazole-Containing Benzo[d]oxazoles

A series of 2-thioalky1-5-(4H-1,2,4-triazol-4-yl)benzo[d]oxazoles were designed and synthesized. Their anticonvulsant activities were evaluated using maximal electroshock shock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models in mice. The neurotoxicity was evaluated with rotarod test. The pharmacology results showed that most compounds exhibited anticonvulsant activity in MES and Sc-PTZ models. Among them, 2-(3-fluobenzyl)thio-5-(4H-1,2,4-triazol-4-yl)benzo[d]oxazole (Si) was the most potent with ED50 value of 11.4 and 31.7 mg/kg in MES and Sc-PTZ models, respectively. The TD50 value of 51 was 611.0 mg/kg, which resulted in the protective index (PI=TD50/ED50) value of 53.6 and 19.3. The pretreatment of thiosemicarbazide (an inhibitor of gamma-aminobutyric acid synthesis enzyme) significantly decreased the active of 51 in MES, which suggested that the GABAergic system may contribute at least in part to the anticonvulsive action.