College of Pharmacy, Yanbian University, No. 977 Park Road, Yanji, Jilin, China.
Med Chem. 2010 Sep;6(5):313-20. doi: 10.2174/157340610793358855.
The present study describes the chemical synthesis and anticonvulsant activity evaluation of a series of 7-alkoxy-triazolo-[3, 4-b]benzo[d]thiazoles. Most compounds exhibited good anticonvulsant activity in the Maximal electroshock (MES) test. And the structure-activity relationships (SAR) were analyzed. Among the compounds studied, 7-octyloxy-triazolo-[3, 4-b]benzo[d]thiazole (5g) was found to be the most potent compound with a median effective dose (ED(50)) value of 8.0 mg/kg and a protective index (PI) value of 15.0, possessing better anticonvulsant activity and higher safety than marketed drugs carbamazepine and phenytoin. The mechanism study of compound 5g showed that it displayed broad spectrum activity in several models, and it is likely to have several mechanisms of action (including inhibiting voltage-gated ion channels and GABAergic activity).
本研究描述了一系列 7-烷氧基-三唑并-[3,4-b]苯并[d]噻唑的化学合成及抗惊厥活性评价。大多数化合物在最大电休克（MES）试验中表现出良好的抗惊厥活性。并分析了构效关系（SAR）。在所研究的化合物中，发现 7-辛氧基-三唑并-[3,4-b]苯并[d]噻唑（5g）是最有效的化合物，其半数有效剂量（ED（50））值为 8.0mg/kg，保护指数（PI）值为 15.0，具有比市售药物卡马西平和苯妥英更好的抗惊厥活性和更高的安全性。化合物 5g 的机制研究表明，它在几种模型中表现出广谱活性，可能具有多种作用机制（包括抑制电压门控离子通道和 GABA 能活性）。
