New 1,2-diaryl-4-substituted-benzylidene-5-4H-imidazolone derivatives: Design, synthesis and biological evaluation as potential anti-inflammatory and analgesic agents.

A new series of 1,2-diaryl-4-substituted-benzylidene-5-4H-imidazolone derivatives 10a-h was designed and synthesized for evaluation as selective COX-2 inhibitors, anti-inflammatory agents and as analgesic agents. All compounds were more selective for COX-2 isozyme and showed good in vivo anti-inflammatory activity. Compounds 10a, 10b, 10e and 10f were the most COX-2 selective compounds (S.I.=10.76, 10.87, 8.69 and 9.14 respectively), the most potent anti-inflammatory derivatives (ED50 =65.7, 60.2, 76.3 and 107.4μmol/kg respectively) in comparison with Celecoxib (COX-2 S.I.=8.61, ED50 =82.2μmol/kg) and were less ulcerogenic (ulcer indexes=1.22-3.02) than Ibuprofen (ulcer index=20.25) and comparable to Celecoxib (ulcer index=2.93). The four derivatives (10a, 10b, 10e and 10f) showed considerable analgesic activities which are clearly parallel to their anti-inflammatory activities.