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

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.

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

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-pyrrolo1,2-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-pyrrolo1,2-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.