2,3-Diarylcyclopentenones as orally active, highly selective cyclooxygenase-2 inhibitors.
Article Details
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Black WC, Brideau C, Chan CC, Charleson S, Chauret N, Claveau D, Ethier D, Gordon R, Greig G, Guay J, Hughes G, Jolicoeur P, Leblanc Y, Nicoll-Griffith D, Ouimet N, Riendeau D, Visco D, Wang Z, Xu L, Prasit P
2,3-Diarylcyclopentenones as orally active, highly selective cyclooxygenase-2 inhibitors.
J Med Chem. 1999 Apr 8;42(7):1274-81.
- PubMed ID
- 10197970 [ View in PubMed]
- Abstract
Cyclopentenones containing a 4-(methylsulfonyl)phenyl group in the 3-position and a phenyl ring in the 2-position are selective inhibitors of cyclooxygenase-2 (COX-2). The selectivity for COX-2 over COX-1 is dramatically improved by substituting the 2-phenyl group with halogens in 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) are particularly interesting as potential antiinflammatory agents with reduced side-effect profiles. Both exhibit good oral bioavailability and are potent in standard models of pain, fever, and inflammation yet have a much reduced effect on the GI integrity of rats compared to standard nonsteroidal antiflammatory drugs.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Celecoxib Prostaglandin G/H synthase 2 IC 50 (nM) 2 N/A N/A Details Celecoxib Prostaglandin G/H synthase 2 IC 50 (nM) 1000 N/A N/A Details Rofecoxib Prostaglandin G/H synthase 1 IC 50 (nM) 1700 N/A N/A Details Rofecoxib Prostaglandin G/H synthase 1 IC 50 (nM) 1900 N/A N/A Details Rofecoxib Prostaglandin G/H synthase 2 IC 50 (nM) 20 N/A N/A Details Rofecoxib Prostaglandin G/H synthase 2 IC 50 (nM) 500 N/A N/A Details