title: Spectral and crystallographic study of pyridinic analogues of nimesulide: determination of the active form of methanesulfonamides as COX-2 selective inhibitors.
abstract: Compound 7, N-(3-phenoxy-4-pyridinyl)trifluoromethanesulfonamide, showed in vitro (whole blood assay) a strong inhibitory activity on the two cyclooxygenase (COX) enzymes (IC(50)(COX-1) = 2.2 microM and IC(50)(COX-2) = 0.4 microM), being more active but less COX-2-selective than nimesulide. Physicochemical studies and structural analyses indicated that the anionic sulfonamidate species seemed to be the active form of methanesulfonamides, which optimally interacted with the COX enzymes' active sites.
authors.affiliation: Natural and Synthetic Drugs Research Center, Department of Medicinal Chemistry, Université de Liège, 1, Avenue de l'Hôpital, Tour 4(+5) Sart-Tilman, Belgium. f.julemont@ulg.ac.be
authors.forename: Fabien
authors.initials: F
authors.lastname: Julémont
authors.forename: Xavier
authors.initials: X
authors.lastname: de Leval
authors.forename: Catherine
authors.initials: C
authors.lastname: Michaux
authors.forename: Jacques
authors.initials: J
authors.lastname: Damas
authors.forename: Caroline
authors.initials: C
authors.lastname: Charlier
authors.forename: François
authors.initials: F
authors.lastname: Durant
authors.forename: Bernard
authors.initials: B
authors.lastname: Pirotte
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dogné
mesh_terms: D000631:Aminopyridines / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000838:Anions; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D018360:Crystallography, X-Ray; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D004487:Edema / Q000188:drug therapy; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D051381:Rats; D017208:Rats, Wistar; D013055:Spectrophotometry, Infrared; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000631:Aminopyridines; D000838:Anions; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; C468797:N-(3-phenoxy-4-pyridinyl)trifluoromethanesulfonamide; D013449:Sulfonamides; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; C012655:nimesulide