Chinese Journal of Organic Chemistry >
Synthesis and Evaluation of the Anticonvulsant Activities of Triazole-Containing Benzo[d]oxazoles
Received date: 2016-04-13
Revised date: 2016-05-15
Online published: 2016-06-02
Supported by
Project supported by the National Natural Science Foundation of China (No.21562028), the Natural Science Foundation of Jiangxi Province (Nos.20151BAB213008, 20142BAB215022), the Youth Science Foundation of JiangXi Educational Committee (No.GJJ14570) and the Doctoral Foundation of Jinggangshan University (No.JZB1316).
A series of 2-thioalkyl-5-(4H-1,2,4-triazol-4-yl)benzo[d]oxazoles were designed and synthesized. Their anticon-vulsant 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 (5i) 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 5i 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 γ-aminobutyric acid synthesis enzyme) significantly decreased the active of 5i in MES, which suggested that the GABAergic system may contribute at least in part to the anticonvulsive action.
Key words： antiepileptic drugs; anticonvulsant; benzo[d]oxazole; triazole; MES; Sc-PTZ
Tan Yuede , He Xiaoyan , Rao Baoqi , Cheng Binbin , Song Mingxia , Deng Xianqing . Synthesis and Evaluation of the Anticonvulsant Activities of Triazole-Containing Benzo[d]oxazoles[J]. Chinese Journal of Organic Chemistry, 2016 , 36(10) : 2449 -2455 . DOI: 10.6023/cjoc201604027
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