Institute of Neurosurgery, Inner Mongolia University for Nationalities, Tongliao, China.
Arch Pharm Res. 2010 May;33(5):655-62. doi: 10.1007/s12272-010-0502-0. Epub 2010 May 29.
Using 6-hydroxy-3,4-dihydro-2(1H)-quinolone as the starting material, a series of 1-formamide-triazolo[4, 3-a]quinoline derivatives (6a-6n) was synthesized, the anticonvulsant effect and neurotoxicity of the compounds was calculated with maximal electroshock test and rotarod tests with intraperitoneally injected in KunMing mice. The results demonstrated that compound 7-(hexyloxy)-4,5-dihydro-[1,2,4] triazolo[4,3-a]quinoline-1-carboxamide (6d) was the most active one and also had the lowest toxicity. In the anti-maximal electroshock potency test, it showed median effective dose (ED(50)) of 30.1 mg/kg, median toxicity dose (TD(50)) of 286 mg/kg, and the protective index of 9.5 which is greater than the reference drug carbamazepine with the protective index value of 6.0.
以 6-羟基-3,4-二氢-2(1H)-喹啉为起始原料，合成了一系列 1-甲酰胺-三唑并[4,3-a]喹啉衍生物（6a-6n）。采用最大电休克试验和旋转棒试验，对化合物的抗惊厥作用和神经毒性进行了计算，采用腹腔注射昆明种小鼠进行试验。结果表明，化合物 7-（己氧基）-4,5-二氢-[1,2,4]三唑并[4,3-a]喹啉-1-甲酰胺（6d）活性最高，毒性最低。在抗最大电休克作用试验中，化合物 6d 的 ED50 为 30.1mg/kg，TD50 为 286mg/kg，保护指数为 9.5，大于参考药物卡马西平的保护指数 6.0。
