2,3-Diarylcyclopentenones as Orally Active, Highly Selective Cyclooxygenase-2 Inhibitors
| Autor: | P. Jolicoeur, P. Prasit, R. Gordon, Christine Brideau, Stella Charleson, Denis Riendeau, Deborah A. Nicoll-Griffith, Gillian Greig, Denise M. Visco, Diane Ethier, C. Chan, Nathalie Ouimet, Yves Leblanc, Zhaoyin Wang, Greg Hughes, Lijing Xu, W. C. Black, Jocelyne Guay, David Claveau, Nathalie Chauret |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Male
Fever Stereochemistry Analgesic Biological Availability CHO Cells Cyclopentanes Carrageenan Transfection Chemical synthesis Cell Line Sulfone Rats Sprague-Dawley Prostaglandin-endoperoxide synthase 2 Structure-Activity Relationship chemistry.chemical_compound Oral administration Cricetinae Microsomes Drug Discovery Animals Edema Humans Phenyl group Cyclooxygenase Inhibitors Sulfones Cyclooxygenase 2 Inhibitors biology Chemistry Membrane Proteins Analgesics Non-Narcotic Arthritis Experimental Rats Isoenzymes Cyclooxygenase 2 Hyperalgesia Prostaglandin-Endoperoxide Synthases Rats Inbred Lew Enzyme inhibitor Cyclooxygenase 1 biology.protein Molecular Medicine Female Cyclooxygenase Digestive System |
| Zdroj: | Journal of Medicinal Chemistry. 42:1274-1281 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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