Abstract
Incorporation of a spacer group between the central scaffold and the aryl ring resulted in a new cyclooxygenase-2 (COX-2) selective inhibitor core structure, 3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)(2-pyridyl) phenyl ketone (20), with COX-2 IC50 = 0.25 microM and COX-1 IC50 = 14 microM (human whole blood assay). Compound 20 was orally active in the rat air pouch model of inflammation, inhibiting white blood cell infiltration and COX-2-derived PG production. Our data support the identification of a novel COX-2 selective inhibitor core structure exemplified by 20.
MeSH terms
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Administration, Oral
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Animals
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Carrageenan
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / chemical synthesis*
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Cyclooxygenase Inhibitors / chemistry
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Cyclooxygenase Inhibitors / pharmacology
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Dinoprostone / antagonists & inhibitors
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Dinoprostone / biosynthesis
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Inflammation / chemically induced
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Inflammation / metabolism
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Male
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Prostaglandin-Endoperoxide Synthases / metabolism*
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Pyridines / chemical synthesis*
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Pyridines / chemistry
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Pyridines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Sulfones / chemical synthesis*
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Sulfones / chemistry
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Sulfones / pharmacology
Substances
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3-(4-(methylsulfonyl)phenyl)-5-(trifluoromethyl)(2-pyridyl) phenyl ketone
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Pyridines
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Sulfones
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Carrageenan
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Cyclooxygenase 2
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Prostaglandin-Endoperoxide Synthases
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Dinoprostone