College of Pharmacy, Yanbian University, Yanji City, Jilin, China.
J Enzyme Inhib Med Chem. 2013 Aug;28(4):792-800. doi: 10.3109/14756366.2012.684052. Epub 2012 Sep 20.
With the aim of finding new anticonvulsant drugs, new 6-substituted-[1,2,4]triazolo[3,4-a] (tetrazolo[5,1-a]) phthalazine derivatives (1-34) have been designed and synthesized. All the compounds were evaluated for their anticonvulsant activities using the maximal electroshock test (MES). Most of the synthesized compounds exhibited potent anticonvulsant activities in the MES. The most promising compound 14 showed significant anticonvulsant activity in MES test with ED₅₀ value of 9.3 mg/kg. It displayed a wide margin of safety with protective index much higher than the standard drug Carbamazepine. And the potency of compound 14 against seizures induced by Pentylenetetrazole, Isoniazid, Thiosemicarbazide and 3-Mercaptopropionic acid in the chemical-induced seizure tests suggested that compound 14 displayed wide spectrum of activity in several models.
为了寻找新的抗惊厥药物，我们设计并合成了新的 6-取代-[1,2,4]三唑并[3,4-a]（四唑并[5,1-a]）邻苯二甲酰亚胺衍生物（1-34）。所有化合物均采用最大电休克试验（MES）评估其抗惊厥活性。大多数合成化合物在 MES 中表现出很强的抗惊厥活性。最有前途的化合物 14 在 MES 试验中表现出显著的抗惊厥活性，ED₅₀值为 9.3mg/kg。它具有很高的安全性，保护指数远高于标准药物卡马西平。化合物 14 在化学诱导性惊厥试验中对戊四氮、异烟肼、噻唑烷二酮和 3-巯基丙酸引起的惊厥的作用表明，化合物 14 在几种模型中表现出广谱活性。
