【作者】 魏成喜；

【导师】 全哲山；

【作者基本信息】 延边大学 ， 药物化学， 2008， 硕士

【摘要】 为了寻找具有更好抗惊厥活性及低神经毒性的化合物,本篇论文以6-羟基-3,4-二氢-2(1H)-喹啉酮为起始原料合成了12个2-取代7-庚氧基-4,5-二氢-[1,2,4]三氮唑[4,3-a]喹啉-1-酮衍生物和4个2-取代7-苄氧基-4,5-二氢-[1,2,4]三氮唑[4,3-a]喹啉-1-酮衍生物,对目标化合物,采用小鼠最大电惊厥实验(MES),皮下戊四唑实验(sc-PTZ)测定了其抗惊厥活性,采用旋转法测定了神经毒性。药理实验结果显示目标化合物表现出了较强的抗惊厥活性,其中化合物4b对MES实验的半数有效量为8.18 mg/kg,保护指数为39,明显高于多种上市药品,如:苯妥英纳,卡马西平,苯巴比妥和丙戊酸纳(保护指数的范围1.6-8.1);活性也高于先导化合物3。该结论证明喹啉并三氮唑化合物具有被开发为新型癫痫治疗药的优良品质。更多还原

【Abstract】 To Find compounds with better anticonvulsant activity and lower neurotoxicity,twelve 2-substituted-7-heptyloxy-4,5-dihydro-[1,2,4]-triazolo[4,3-a]quinolin-1（2H）-ones and four 2-substituted-7-benzyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-1（2H）-ones derivatives were synthesized using 6-hydroxy-3,4-dihydro-2（1H）-quinolone as a starting material,and their anticonvulsant activities were evaluated by the maximal electroshock test（MES） and the subcutaneous pentylenetetrazole test（sc-PTZ） and their neurotoxicities were measured by the rotarod neurotoxicity test（Tox）.The results showed that 2-propionyl-7-（heptyloxy）-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolin-1（2 H）-one（4b） was the most potent with ED₅₀ values of 8.18 mg/kg and the protective index(PI = TD₅₀/ED₅₀) values of 39 in the MES.The PI values of 4b was better than that of the marketed drugs phenytoin,carbamazepin, phenobarbital and valproate which have PI values in the range of 1.6-8.1 in the MES test.It also better than the lead compound 3.It was found that [1,2,4]triazole[4,3-a]quinolin-1-ones possess the potent of being explored to be a new anticonvulsant agent.更多还原