Synthesis and Evaluation of the Anticonvulsant Activities of Triazole-Containing Benzo[d]oxazoles
Synthesis and Evaluation of the Anticonvulsant Activities of Triazole-Containing Benzo[d]oxazoles
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DOI：
10.6023/cjoc201604027
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发表时间：
2016-10-01
影响因子：
1.9
通讯作者：
Deng, Xianqing
中科院分区：
文献类型：
--
作者：
Tan, Yuede;He, Xiaoyan;Deng, Xianqing
设计并合成了一系列2-硫代烷基-5-（4 H-1，2，4-三唑-4-基）苯并[d]恶唑类化合物。采用小鼠最大电休克（MES）和皮下注射戊四唑（scPTZ）癫痫模型评价其抗惊厥活性。神经毒性采用转棒试验评价。药理实验结果表明，大部分化合物在MES和Sc-PTZ模型中表现出抗惊厥活性。其中2-（3-氟苄基）硫代-5-（4 H-1，2，4-三唑-4-基）苯并[d]恶唑（Si）的作用最强，在MES和Sc-PTZ模型中的ED 50值分别为11.4和31.7 mg/kg。51的TD 50值为611.0 mg/kg，这导致保护指数（PI= TD 50/ED 50）值为53.6和19.3。氨基硫脲（γ-氨基丁酸合成酶抑制剂）预处理可显著降低MES中51的活性，提示GABA能系统可能参与了其抗惊厥作用。
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.