3-芳基-2-甲基-1-吡咯并[1,2-a]吡嗪酮类衍生物的合成和抗炎镇痛作用  

Synthesis and anti-inflammatory and analgesic activities of 3-aryl-2-methyl-1-pyrrolo[1,2-a]pyrazinones

作　　者：王绯[1] 郑红[1] 张守芳[1] 

机构地区：[1]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》2004年第4期215-218,共4页Chinese Journal of Medicinal Chemistry

摘　　要：目的研究 3 芳基 2 甲基 1 吡咯并 [1,2 a]吡嗪酮 (2 )类化合物抗炎镇痛作用的构效关系。方法通过吡咯 2 甲酸甲酯与α 溴代芳基乙酮的烃基化反应 ,制得 1 (2 氧代 2 芳基 )乙基吡咯 2 甲酸甲酯 (4 ) ,4与甲胺反应经过环合直接生成目的化合物 2 ;用小鼠测试了所合成化合物的抗炎镇痛活性。结果与结论合成了 15个目标化合物 ;小鼠试验表明 ,一些所合成的化合物具有明显的抗炎和 /或镇痛作用 ,其中化合物 2o的作用活性与阳性对照药布洛芬相似。Aim To study the structure-activity relationship(SAR)of the title compounds and search for new anti-inflammatory and analgesic agents.Methods 3-Aryl-2-methyl-1-pyrrolo[1,2-a]pyrazinones(2 )were designed based on CoMFA and SAR.The title compounds 2 were synthesized from methyl pyrrole-2-carboxylate via N -alkylation and a novel cyclization.Methyl 1-(2-oxo-2-aryl)ethylpyrrole-2-carboxylate(10 )reacted with methylamine to form the ring directly.Ten compounds were prepared from methyl pyrrole-2-carboxylate by N -alkylation.The anti-inflammatory and analgesic activities were tested in mice.Results and Conclusion Fifteen 3-aryl-2-methyl-1-pyrrolo[1,2-a]pyrazinones were synthesized.Most of the compounds showed remarkable anti-inflammatory and/or analgesic activities in mice.The activities of compound 2o are equal to those of ibuprofen.

关 键 词：药物化学 制备 化学合成 3-芳基-2-甲基-1-吡咯并[1 2-a]吡嗪酮 抗炎 镇痛 

分 类 号：R914[医药卫生—药物化学]