1131479-20-3Relevant academic research and scientific papers
Synthesis of celecoxib analogues possessing a N-difluoromethyl-1,2- dihydropyrid-2-one 5-lipoxygenase pharmacophore: Biological evaluation as dual inhibitors of cyclooxygenases and 5-lipoxygenase with anti-inflammatory activity
Chowdhury, Morshed A.,Abdellatif, Khaled R. A.,Dong, Ying,Das, Dipankar,Suresh, Mavanur R.,Knaus, Edward E.
experimental part, p. 1525 - 1529 (2010/01/16)
A novel class of 1-(4-methanesulfonylphenyl and 4-aminosulfonylphenyl)-5- [4-(1-difluoromethyl-1,2- dihydropyrid-2-one)]-3-trifluoromethyl-1 H-pyrazole hybrid cyclooxygenase-2 (COX-2)/5-lipoxygenase (5-LOX) inhibitory anti-inflammatory agents was designed. Replacement of the tolyl ring present in celecoxib by the N-difluoromethyl-1,2-dihydropyrid-2-one moiety provided compounds showing dual selective COX-2/5-LOX inhibitory activities. 1-(4-Aminosulfonylphenyl)-5-[4-(1-difluoromethyl-1,2-dihydropyrid-2-one)] -3-trifluoromethyl-1 H-pyrazole exhibited good anti-inflammatory (AI) activity (ED50 = 27.7 mg/kg po) that compares favorably with the reference drugs celecoxib (ED50 = 10.8 mg/kg po) and ibuprofen (ED50 = 67.4 mg/kg po). The N-difluoromethyl-1,2-dihydropyridin-2-one moiety provides a novel 5-LOX pharma- cophore for the design of cyclic hydroxamic mimetics for exploitation in the development of COX-2/5-LOX inhibitory AI drugs.
