Deng Xian-Qing, Song Ming-Xia, Gong Guo-Hua, Wang Shi-Ben, Quan Zhe-Shan
Medical College, Jinggangshan University, Ji'an , JiangXi, 343009, China.
Institute of Medicinal Chemistry and pharmacology, Inner Mongolia University for Nationalities, Tongliao, China .
Iran J Pharm Res. 2014 Spring;13(2):459-69.
Epilepsy is the most frequent nearological affiction and afflicts 1% about of the world's population. Currently there is an urgent need for the development of novel anticonvulsants with higher levels of potency and lower levels of toxicity. In this paper, a series of new 6-(substituted-phenyl)thiazolo[3,2-b][1,2,4]triazole derivatives were synthesized and tested for their anticonvulsant activities using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (PTZ) screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotarod test. In these compounds, 6-(4-fluorophenyl)thiazolo[3,2-b][1,2,4]triazole (3c) showed selective protection against the MES seizures with an ED50 value of 49.1 mg/Kg and a TD50 value of 94.1 mg/Kg, which provided compound 3c a protective index (PI = TD50/ED50) of 1.9 in the MES test. 6-(4-Propoxyphenyl)thiazolo[3,2-b][1,2,4]triazole (5b) was found to be active in both models, i.e. MES test and PTZ test. In the PTZ screen, compound 5b gave an ED50 of 63.4 mg/Kg and a TD50 of 105.6 mg/Kg, resulting in a PI value of 1.7 which is higher than carbamazepine.
癫痫是最常见的神经系统疾病，影响着全球约1%的人口。目前迫切需要开发效力更高、毒性更低的新型抗惊厥药物。本文合成了一系列新的6-（取代苯基）噻唑并[3,2-b][1,2,4]三唑衍生物，并使用最大电休克（MES）和皮下注射戊四氮（PTZ）筛选试验检测它们的抗惊厥活性，这两种筛选试验是早期鉴定候选抗惊厥药物最广泛使用的癫痫模型。通过转棒试验测定它们的神经毒性。在这些化合物中，6-（4-氟苯基）噻唑并[3,2-b][1,2,4]三唑（3c）对MES诱发的癫痫表现出选择性保护作用，其半数有效剂量（ED50）值为49.1mg/Kg，半数中毒剂量（TD50）值为94.1mg/Kg，这使得化合物3c在MES试验中的保护指数（PI = TD50/ED50）为1.9。6-（4-丙氧基苯基）噻唑并[3,2-b][1,2,4]三唑（5b）在MES试验和PTZ试验这两种模型中均具有活性。在PTZ筛选试验中，化合物5b的ED50为63.4mg/Kg，TD50为105.6mg/Kg，PI值为1.7，高于卡马西平。
