7-取代苯氧基-4,5-二氢-1,2,4-三唑并[4,3-a]喹啉和喹啉-1(2H)-酮衍生物的合成及抗惊厥活性  

Synthesis and Anticonvulsant Activity Study of 7-Substituted Phenoxyl-4,5-dihydro[1,2,4]triazolo[4,3-a]quinolines and Quinoline-1(2H)-ones

作　　者：金云哲[1] 关丽萍[2] 赵立明[2] 朴虎日[2] 全哲山[1] 

机构地区：[1]延边大学长白山生物功能因子省部共建教育部重点实验室,延吉133002 [2]延边大学药学院,延吉133000

出　　处：《有机化学》2007年第12期1567-1572,共6页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.30460151);教育部重点(No.2007-24)资助项目.

摘　　要：合成了7-取代苯氧基-4,5-二氢-1,2,4-三唑并[4,3-a]喹啉(3a～3g)和7-取代苯氧基-4,5-二氢-1,2,4-三唑并[4,3-a]喹表明啉-1(2H)-酮(4a～4g)类衍生物.以最大电惊厥法和戊四唑法测定了抗惊厥活性,以旋转棒法测定了神经毒性.结果表明,化合物7-(4-氟苯氧基)-4,5-二氢-1,2,4-三唑并[4,3-a]喹啉-1(2H)-酮(4c)显示最强的抗惊厥作用和低的神经毒性,其抗电惊厥ED50为6.8mg/kg,神经毒性TD50为88.0mg/kg,保护指数PI为12.9,明显优于对照药苯妥英钠.A series of 7-（substituted phenoxyl）-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinolines and 7-（substituted phenoxyl）-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline-1（2H）-ones were synthesized. The convulsant effect and neurotoxicity of the compound were determined with maximal electroshock test （MES）, pentylenetetrazol （PTZ） method and rotarod test intraperitoneally in mice. 7-（4-Fluorophenyloxy）-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline-l（2H）-one （4c） was the most active and also has the lowest toxicity. In the anti-MES potency test, 4c showed a medial effective dose （EDs0） of 6.8 mg/kg, a medial toxicity dose （TDs0） of 88.0 mg/kg, and the protective index （PI） of 12.9. The PI value of compound 4c was better than that of the marketed drug phenytoin.

关 键 词：三唑 喹啉 1 2 4-三唑并[4 3-a]喹啉 合成 抗惊厥 

分 类 号：O626[理学—有机化学]