Citation: 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 shu

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

1.
Basic Medical and Pharmacy College, Department of Medicine, Jinggangshan University, Ji'an 343009

Corresponding author: Deng Xianqing, dengxianqing1121@126.com
Received Date: 13 April 2016
Revised Date: 15 May 2016

Fund Project: the Youth Science Foundation of JiangXi Educational Committee No.GJJ14570the Natural Science Foundation of Jiangxi Province Nos.20151BAB213008，20142BAB215022Project supported by the National Natural Science Foundation of China No.21562028and the Doctoral Foundation of Jinggangshan University No.JZB1316

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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.
- antiepileptic drugs,
- anticonvulsant,
- benzo[d]oxazole,
- triazole,
- MES,
- Sc-PTZ
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沈阳化工大学材料科学与工程学院沈阳 110142