Novel 2-(4-methylsulfonylphenyl)pyrimidine derivatives as highly potent and specific COX-2 inhibitors

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 IC50 = 2.4–0.3 nM and 80- to 780-fold more selective than rofecoxib).

New series of pyrimidines I were synthesized and evaluated as cyclooxygenase-2 (COX-2) inhibitors. Compounds 8, 67, 69, 71, 82 and 83 were highly potent and specific COX-2 inhibitors (HWB COX-2 IC50 = 2.4–0.3 nM and 80- to 780-fold more selective than rofecoxib).Figure optionsDownload as PowerPoint slide