School of Food, Drug & Medicine Zhejiang Ocean University, Zhoushan 316000, PR China.
Med Chem. 2012 Nov;8(6):1076-83. doi: 10.2174/1573406411208061076.
In this study, a novel series of 7-substituted-[1,2,4]triazolo[4,3-f]pyrimidine derivatives was synthesized as potential anticonvulsant agents. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test, and their neurotoxicities were evaluated by the rotarod neurotoxicity test. The pharmacological results showed that the compound 3i (7-(4-chlorophenoxy)-[1,2,4]triazolo[4,3-f]pyrimidine) was among the most active agent with median effective dose (ED(50)) value of 34.7 mg/kg, median toxicity dose (TD(50)) of 262.9 mg/kg, and providing a protective index (PI=TD(50)/ED(50)) value of 7.6. The compound 3i also showed oral activity against MES-induced seizures and lower oral neurotoxicity. The compound 3i demonstrated antagonistic activity against seizures induced by PTZ, ISN, 3-MP and thiosemicarbazide.
在这项研究中，我们合成了一系列新型的 7-取代-[1,2,4]三唑并[4,3-f]嘧啶衍生物，作为有潜力的抗惊厥药物。我们通过最大电休克（MES）测试评估了它们的抗惊厥活性，通过旋转棒神经毒性测试评估了它们的神经毒性。药理结果表明，化合物 3i（7-(4-氯苯氧基)-[1,2,4]三唑并[4,3-f]嘧啶）是最具活性的化合物之一，其半数有效剂量（ED(50)）值为 34.7mg/kg，半数毒性剂量（TD(50)）为 262.9mg/kg，保护指数（PI=TD(50)/ED(50)）值为 7.6。化合物 3i 还对 MES 诱导的癫痫发作具有口服活性，且口服神经毒性较低。化合物 3i 对 PTZ、ISN、3-MP 和硫代卡巴肼诱导的癫痫发作具有拮抗活性。
