3,4-二氢吡咯[1,2-a]吡嗪-1-酮衍生物的合成及抗炎镇痛作用  

Synthesis,anti-inflammatory and analgesic activities of (2H)-2-cyclohexyl-3,4-dihydropyrrolo[1,2-a] pyrazin-1-one derivatives

作　　者：付德才[1] 周鸿娟[2] 狄蕊[1] 张守芳[3] 

机构地区：[1]河北科技大学化学与制药工程学院,河北石家庄050018 [2]河北师范大学实验中心,河北石家庄050016 [3]沈阳药科大学制药工程学院,辽宁沈阳110016

出　　处：《中国药物化学杂志》2006年第1期23-26,共4页Chinese Journal of Medicinal Chemistry

摘　　要：目的研究(2H)-2-环己基-3,4-二氢吡咯[1,2-a]吡嗪-1-酮衍生物抗炎镇痛作用的构效关系。方法以2-吡咯甲酸甲酯为原料,经取代、环合,制备(2H)-2-环己基-3,4-二氢吡咯[1,2-a]吡嗪-1-酮(3);通过Friedel-Crafts酰基化反应,制得其6-酰基衍生物4a^4j。用小鼠测试了所合成化合物的抗炎和镇痛活性。结果与结论合成了10个未见文献报道的新化合物4a^4j,其结构经MS1、H-NMR分析确证。抗炎镇痛试验表明,有些化合物具有明显的抗炎和/或镇痛作用,其中化合物4d的活性与对照药布洛芬相当。Aim To study the structure-activity relationships of 6-aryl derivatives of （2H）-2-cyclohexyl-3, 4- dihydropyrrolo[1,2-a]pyrazin-l-one and to search for new anti-inflammatory and analgesic agents. Method （2H）-2-cyclohexyl-3, 4-dihydropyrrolo [ 1, 2-a] pyrazin-l-one was synthesized from methyl pyrrole-2-car- boxylate via substitution and cyclization, and the target compounds 6-aryl derivatives were obtained by Friedel-Crafts reaction. Their anti-inflammatory and analgesic activities were tested in xylene-induced mice ear edema and acetic acid-induced mice writhing. Results and conclusion Ten new 6-aryl derivatives were synthesized and their structures were confirmed by MS, ^1H-NMR. Most of the compounds show remarkable anti-inflammatory and/or analgesic activities in mice, and the activities of compound 4d is comparable to ibuprofen.

关 键 词：药物化学 构效关系 化学合成 (2H)-2-环已基-3 4-二氢吡咯[1 2-a]吡嗪-1-酮 6-酰基衍生物 抗炎 镇痛 

分 类 号：R914.5[医药卫生—药物化学]