5,6-二芳基-2,3-二氢-1-吡咯里嗪酮类化合物的合成及抗炎镇痛活性

5,6-DIARYL-2,3-DIHYDRO-1-PYRROLIZINONE DERIVATIVES SYNTHESIS AND ANTIINFLAMMATORY AND ANALGESIC ACTIVITIES

目的 寻找高效低毒、有抗炎镇痛活性的新的吡咯里嗪酮类化合物。方法 以二芳基取代杂环类COX 2选择性抑制剂为模板 ,以吡里酮为母体 ,设计并合成了 5 ,6 二芳基 2 ,3 二氢 1 吡咯里嗪酮类化合物。用IR ,1HNMR和MS确定其结构。用二甲苯致小鼠耳肿胀法和小鼠醋酸扭体法测定这些化合物的 ( po 2 0 0mg·kg-1)抗炎及镇痛活性。结果 合成了 17个新化合物 ( 1- 17)。生物实验结果显示 ,多数化合物有一定的抗炎和 (或 )镇痛活性。结论 化合物 3,8,11,14和 15抗炎活性优于对照药布洛芬 ;化合物 9,10和 11镇痛活性接近于对照药布洛芬 。

AIM To search for more potent and less toxic antiinflammatory and analgesic activity compounds. METHODS A series of 5,6-diaryl-2,3-dihydro-1-pyrrolizinone derivatives were designed and synthesized based on the structures of diarylheterocyclic COX-2 selective inhibitors. Their structures were determined on the basis of spectal data (IR, MS and 1HNMR). Their antiinflammatory and analgesic activities in vivo were tested by xylene-induced mouse ear edema model and acetic acid-induced mouse writhing model po dose of 200 mg·kg -1 . RESULTS Seventeen new compounds (1-17) were synthesized. Many of these compounds showed antiinflammatory and analgesic activities. CONCLUSION Compound 3, 8, 11, 14 and 15 showed antiinflammatory activities more potent than ibuprofen. Compound 9, 10 and 11 showed analgesic activities comparable to ibuprofen. These compounds are regarded to be promising to develop new potent drugs.