Synthesis and Anticonvulsant Activities of Some Triazolothiadiazole Derivatives
Synthesis and Anticonvulsant Activities of Some Triazolothiadiazole Derivatives
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部分三唑并噻二唑衍生物的合成及抗惊厥活性
DOI：
10.1002/ardp.201100326
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发表时间：
2012-07-01
影响因子：
5.1
通讯作者：
Quan, Zhe-Shan
中科院分区：
文献类型：
--
作者：
Deng, Xian-Qing;Dong, Zheng-Qi;Quan, Zhe-Shan
本文报道了6-substituted-[1，2，4]triazolo[3，4-b][1，3，4]thiadiazole衍生物(4a4x)及其部分脱氢产物5，6-dihydro-6-substituted-[1，2，4]triazolo[3，4-b][1，3，4]thiadiazole衍生物(5a5n)的合成和抗惊厥活性评价。生物评价结果表明，4a4x系列中的大多数化合物在最大电击试验中都显示出较强的抗惊厥活性。其中，6-(4-chlorophenyl)-[1，2，4]triazolo[3，4-b][1，3，4]thiadiazole(4h)的ED50值为23.7 mg/kg，等电点为10.8，是最有希望的候选者。此外，化合物4h对戊四氮、3-巯基丙酸和荷包牡丹碱所致惊厥的抑制作用表明，化合物4h在多种模型中均表现出广谱活性，可能通过影响GABA能系统发挥其抗惊厥作用。
The present study describes the synthesis and anticonvulsant activity evaluation of 6-substituted-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives (4a4x) and their partially dehydrogenated products 5,6-dihydro-6-substituted-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives (5a5n). The bioevaluation demonstrated that most compounds in the series of 4a4x exhibited potent anticonvulsant activity in the maximal electroshock test. Among which, 6-(4-chlorophenyl)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole (4h) emerged as the most promising candidate on the basis of its favorable ED50 value of 23.7?mg/kg and PI value of 10.8. In addition, the potency of compound 4h against seizures induced by pentylenetetrazole, 3-mercaptopropionic acid, and bicuculline in the chemical-induced seizure tests suggested that compound 4h displayed broad-spectrum activity in several models, and it may exert its anticonvulsant activity through affecting the GABAergic system.