title: A new potential cyclooxygenase-2 inhibitor, pyridinic analogue of nimesulide.
abstract: In this paper, the binding mode of original pyridinic compounds structurally related to nimesulide, a preferential cyclooxygenase (COX)-2 inhibitor, is analyzed by docking simulations in order to understand structure-activity relationships of this family. Structural modifications are proposed to reverse the selectivity of the more active inhibitor of the series characterized by a preferential activity on COX-1. On the basis of these modifications, a new compound with a bromo substituent was designed and showed a COX-2 selective inhibition.
authors.affiliation: Laboratoire Chimie Biologique Structurale, Facultés Universitaires N.-D. de la Paix, 61, rue de Bruxelles, B-5000 Namur, Belgium. catherine.michaux@fundp.ac.be
authors.forename: Catherine
authors.initials: C
authors.lastname: Michaux
authors.forename: Caroline
authors.initials: C
authors.lastname: Charlier
authors.forename: Fabien
authors.initials: F
authors.lastname: Julémont
authors.forename: Xavier
authors.initials: X
authors.lastname: de Leval
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Dogné
authors.forename: Bernard
authors.initials: B
authors.lastname: Pirotte
authors.forename: François
authors.initials: F
authors.lastname: Durant
mesh_terms: D018360:Crystallography, X-Ray; D051545:Cyclooxygenase 1 / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000187:drug effects*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D011725:Pyridines; D013449:Sulfonamides; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C012655:nimesulide