| Abstract
| - Cyclopentenones containing a 4-(methylsulfonyl)phenyl group in the 3-position and a phenylring in the 2-position are selective inhibitors of cyclooxygenase-2 (COX-2). The selectivity forCOX-2 over COX-1 is dramatically improved by substituting the 2-phenyl group with halogensin the meta position or by replacing the phenyl ring with a 2- or 3-pyridyl ring. Thus the 3,5-difluorophenyl derivative 7 (L-776,967) and the 3-pyridyl derivative 13 (L-784,506) areparticularly interesting as potential antiinflammatory agents with reduced side-effect profiles.Both exhibit good oral bioavailability and are potent in standard models of pain, fever, andinflammation yet have a much reduced effect on the GI integrity of rats compared to standardnonsteroidal antiflammatory drugs.
|
