Abstract
New series of 2-(4-methylsulfonylphenyl) and 2-(4-sulfamoylphenyl)pyrimidines were synthesized and evaluated for their ability to inhibit cyclooxygenase-2 (COX-2). COX-1 and COX-2 inhibitory activity of these compounds was determined using purified enzyme (PE) and human whole blood (HWB) assays. Extensive structure-activity relationship (SAR) work was carried out within these series, and a wide number of potent and specific COX-2 inhibitors were identified (HWB COX-2 IC(50)=2.4-0.3nM and 80- to 780-fold more selective than rofecoxib).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cyclooxygenase 2 Inhibitors / chemical synthesis*
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Cyclooxygenase 2 Inhibitors / chemistry
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Cyclooxygenase 2 Inhibitors / pharmacology*
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Inhibitory Concentration 50
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Methylation
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Molecular Structure
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Pyrimidines / chemical synthesis*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology*
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Structure-Activity Relationship
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Sulfur Compounds / chemical synthesis*
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Sulfur Compounds / chemistry
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Sulfur Compounds / pharmacology*
Substances
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Cyclooxygenase 2 Inhibitors
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Pyrimidines
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Sulfur Compounds