2,3-Diarylcyclopentenones as orally active, highly selective cyclooxygenase-2 inhibitors.

Article Details

Citation

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
DrugTargetPropertyMeasurementpHTemperature (°C)
CelecoxibProstaglandin G/H synthase 2IC 50 (nM)2N/AN/ADetails
CelecoxibProstaglandin G/H synthase 2IC 50 (nM)1000N/AN/ADetails
RofecoxibProstaglandin G/H synthase 1IC 50 (nM)1700N/AN/ADetails
RofecoxibProstaglandin G/H synthase 1IC 50 (nM)1900N/AN/ADetails
RofecoxibProstaglandin G/H synthase 2IC 50 (nM)20N/AN/ADetails
RofecoxibProstaglandin G/H synthase 2IC 50 (nM)500N/AN/ADetails