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

doi:10.6023/cjoc201604027

Chin. J. Org. Chem. ›› 2016, Vol. 36 ›› Issue (10): 2449-2455.DOI: 10.6023/cjoc201604027 Previous Articles Next Articles

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含有三唑的苯并[d]噁唑类衍生物的合成及其抗惊厥活性评价

谭月德, 何晓艳, 饶保奇, 程彬彬, 宋明霞, 邓先清

井冈山大学医学部基础医学与药学学院吉安 343009

收稿日期:2016-04-13 修回日期:2016-05-15 发布日期:2016-06-02
通讯作者: 邓先清,E-mail:dengxianqing1121@126.com E-mail:dengxianqing1121@126.com
基金资助:
国家自然科学基金（No.21562028）、江西省自然科学基金项目（Nos.20151BAB213008，20142BAB215022）、江西省教育厅科技计划项目（No.GJJ14570）和井冈山大学博士启动基金（No.JZB1316）资助项目.

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

Tan Yuede, He Xiaoyan, Rao Baoqi, Cheng Binbin, Song Mingxia, Deng Xianqing

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

Received:2016-04-13 Revised:2016-05-15 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).

1. Synthesis and Evaluation of the Anticonvulsant Activities of Triazole-Containing Benzo[d]oxazoles.PDF(2526KB)

Abstract

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

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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]. Chin. J. Org. Chem., 2016, 36(10): 2449-2455.

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含有三唑的苯并[d]噁唑类衍生物的合成及其抗惊厥活性评价

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

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