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

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.