title: Novel 2-(4-methylsulfonylphenyl)pyrimidine derivatives as highly potent and specific COX-2 inhibitors.
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).
authors.affiliation: Department of Research, Faes Farma S.A., Máximo Aguirre 14, 48940 Leioa, Spain.
authors.forename: Aurelio
authors.initials: A
authors.lastname: Orjales
authors.forename: Ramón
authors.initials: R
authors.lastname: Mosquera
authors.forename: Beatriz
authors.initials: B
authors.lastname: López
authors.forename: Roberto
authors.initials: R
authors.lastname: Olivera
authors.forename: Luis
authors.initials: L
authors.lastname: Labeaga
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Núñez
mesh_terms: D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008745:Methylation; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013457:Sulfur Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011743:Pyrimidines; D013457:Sulfur Compounds