5-芳基-1,2-二氢-1-吡咯里嗪酮类化合物的合成及抗炎镇痛作用

Synthesis and antiinflammatory and analgesic activities of 5-aryl-1,2-dihydro-1-pyrrolizinones

目的研究 5 芳基 1,2 二氢 1 吡咯里嗪酮类化合物的抗炎镇痛作用构效关系 ,寻找高效低毒、具有抗炎镇痛活性的新型吡咯里嗪酮衍生物。方法以吡咯里嗪酮为母体 ,设计并合成了 5 芳基 1,2 二氢 1 吡咯里嗪酮类化合物。用二甲苯致小鼠耳肿胀法和小鼠醋酸扭体法测定了该类化合物的抗炎及镇痛活性。结果用两条路线合成了 10个目标化合物 ,经1H NMR和MS确证其结构。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。结论化合物Ⅲ1及Ⅲ5的抗炎活性优于对照药布洛芬 ;化合物Ⅲ5的镇痛活性优于对照药布洛芬 ;其中化合物Ⅲ5的抗炎及镇痛活性均强于对照药布洛芬 ,值得进一步研究。

Aim To study the structure activity relationship(SAR)of the title compounds and search for new potent antiinflammatory and analgesic agents in pyrrolizinones.Methods A series of 5 aryl 1,2 dihydro 1 pyrrolizinone derivatives was prepared with two different synthetic schemes.Their antiinflammatory and analgesic activities were tested by xylene induced mice ear edema model and acetic acid induced mice writhing model.Results Ten new compounds(Ⅲ 1～Ⅲ 10 )were synthesized and their structures were determined by 1H NMR and MS.Some of the prepared compounds showed remarkably antiinflammatory and/or analgesic activities in mice.Conclusion The anti inflammatory activities of compounds Ⅲ 1,Ⅲ 5 were more potent than ibuprofen.Compound Ⅲ 5 is comparable to ibuprofen both in antiinflammatory and analgesic activities,and is regarded as a promising compound for developing a new anti inflammatory agent.