Spectral and Crystallographic Study of Pyridinic Analogues of Nimesulide:
Determination of the Active Form of Methanesulfonamides as COX-2 Selective
Inhibitors

Julémont, Fabien; Leval, Xavier de; Michaux, Catherine; Damas, Jacques; Charlier, Caroline; Durant, François; Pirotte, Bernard; Dogné, Jean-Michel

doi:10.1021/jm020920n.s001

jm020920n_si_001.pdf (499.6 kB)

Spectral and Crystallographic Study of Pyridinic Analogues of Nimesulide: Determination of the Active Form of Methanesulfonamides as COX-2 Selective Inhibitors

journal contribution

posted on 2002-10-03, 00:00 authored by Fabien Julémont, Xavier de Leval, Catherine Michaux, Jacques Damas, Caroline Charlier, François Durant, Bernard Pirotte, Jean-Michel Dogné

Compound 7, N-(3-phenoxy-4-pyridinyl)trifluoromethanesulfonamide, showed in vitro (whole blood assay) a strong inhibitory activity on the two cyclooxygenase (COX) enzymes (IC₅₀(COX-1) = 2.2 μM and IC₅₀(COX-2) = 0.4 μM), 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.