Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, Hamdard Nagar, New Delhi 110062, India.
Eur J Med Chem. 2010 Apr;45(4):1536-43. doi: 10.1016/j.ejmech.2009.12.062. Epub 2010 Jan 13.
Various 3-[4-(substituted phenyl)-1,3-thiazol-2-ylamino]-4-(substituted phenyl)-4,5-dihydro-1H-1,2,4-triazole-5-thiones (7a-t) were designed keeping in view the structural requirements suggested in the pharmacophore model for anticonvulsant activity. Thiazole and triazole moieties being anticonvulsants were clubbed together to get the titled compounds and their in vivo anticonvulsant screening were performed by two most adopted seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Two compounds 7d and 7f showed significant anticonvulsant activity in both the screens with ED(50) values 23.9 mg/kg and 13.4 mg/kg respectively in MES screen and 178.6 mg/kg and 81.6 mg/kg respectively in scPTZ test. They displayed a wide margin of safety with Protective index (PI), median hypnotic dose (HD(50)) and median lethal dose (LD(50)) much higher than the standard drugs.
设计了各种 3-[4-(取代苯基)-1,3-噻唑-2-基氨基]-4-(取代苯基)-4,5-二氢-1H-1,2,4-三唑-5-硫酮（7a-t），这些化合物的结构符合抗惊厥活性的药效团模型所提出的结构要求。噻唑和三唑部分都具有抗惊厥作用，将它们结合在一起得到了标题化合物，并通过两种最常用的癫痫发作模型，最大电休克（MES）和皮下戊四氮（scPTZ）进行了体内抗惊厥筛选。化合物 7d 和 7f 在两种筛选中均表现出显著的抗惊厥活性，MES 筛选中的 ED（50）值分别为 23.9mg/kg 和 13.4mg/kg，scPTZ 测试中的 ED（50）值分别为 178.6mg/kg 和 81.6mg/kg。它们具有很高的安全性，保护指数（PI）、半数催眠剂量（HD（50））和半数致死剂量（LD（50））均远高于标准药物。
