具有抗惊厥活性的2-取代-7-庚氧基-4,5-二氢-[1,2,4]-三唑并[4,3-a]喹啉-1(2H)-酮的合成。
Synthesis of 2-substituted-7-heptyloxy-4,5-dihydro-[1,2,4]-triazolo[4,3-a]quinolin-1(2H)-ones with anticonvulsant activity.
作者信息
Wei Cheng-Xi, Li Fu-Nan, Zhao Long-Xuan, Zhao Li-Ming, Quan Zhe-Shan
机构信息
Key Laboratory of Organism Functional Factors of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, Jilin, PR China.
出版信息
Arch Pharm (Weinheim). 2007 Sep;340(9):491-5. doi: 10.1002/ardp.200700106.
A series of 2-substituted-7-heptyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-1(2H)-ones was synthesized. The anticonvulsant effect and neurotoxicity of the compounds were calculated with maximal electroshock (MES) test, subcutaneous pentylenetetrazole (sc-PTZ), and rotarod tests with intraperitoneally injected mice. Among the synthesized compounds, 2-propionyl-7-heptyloxy-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline-1(2H)-one 4b was the most active one and also had the lowest toxicity. In the anti-MES potency test, it showed median effective dose (ED(50)) of 8.2 mg/kg, median toxicity dose (TD(50)) of 318.3 mg/kg, and the protective index (PI) of 39.0 which is much greater than the PI of the reference drugs phenytoin and carbamazepine.
合成了一系列2-取代-7-庚氧基-4,5-二氢-[1,2,4]三唑并[4,3-a]喹啉-1(2H)-酮。通过最大电休克（MES）试验、皮下注射戊四氮（sc-PTZ）以及对腹腔注射小鼠进行的转棒试验，计算了这些化合物的抗惊厥作用和神经毒性。在合成的化合物中，2-丙酰基-7-庚氧基-4,5-二氢-[1,2,4]三唑并[4,3-a]喹啉-1(2H)-酮4b活性最高且毒性最低。在抗MES效力试验中，它的半数有效剂量（ED(50)）为8.2 mg/kg，半数毒性剂量（TD(50)）为318.3 mg/kg，保护指数（PI）为39.0，远高于参考药物苯妥英和卡马西平的PI。
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