title: Synthesis and biological evaluation of 4,5-diphenyloxazolone derivatives on route towards selective COX-2 inhibitors.
abstract: A series of 3-unsubstituted/substituted-4,5-diphenyl-2-oxo-3H-1,3-oxazole derivatives were prepared as selective cyclooxygenase-2 (COX-2) inhibitors. Among the synthesized compounds, 4-(4-phenyl-3-methyl-2-oxo-3H-1,3-oxazol-5-yl)benzensulfonamide (compound 6) showed selective COX-2 inhibition with a selectivity index of >50 (IC(50)COX-1=>100 microm, IC(50)COX-2=2 microm) in purified enzyme (PE) assay. Compound 6 also exhibited selective COX-2 inhibition in human whole blood assay. Molecular docking studies showed that 6 can be docked into the COX-2 binding site thus providing the molecular basis for its activity.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Gazi University, Taç Sk, 06330 Etiler, Ankara, Turkey.
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Dündar
authors.forename: Serdar
authors.initials: S
authors.lastname: Unlü
authors.forename: Erden
authors.initials: E
authors.lastname: Banoğlu
authors.forename: Antonio
authors.initials: A
authors.lastname: Entrena
authors.forename: Gabriele
authors.initials: G
authors.lastname: Costantino
authors.forename: Maria-Teresa
authors.initials: MT
authors.lastname: Nuñez
authors.forename: Maria-Teresa
authors.initials: MT
authors.lastname: Nunez
authors.forename: Luis
authors.initials: L
authors.lastname: Labeaga
authors.forename: Francisco
authors.initials: F
authors.lastname: Ledo
authors.forename: M Fethi
authors.initials: MF
authors.lastname: Sahin
authors.forename: Ningur
authors.initials: N
authors.lastname: Noyanalpan
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D051546:Cyclooxygenase 2 / Q000097:blood / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis*; D006801:Humans; D020128:Inhibitory Concentration 50; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011485:Protein Binding; D013329:Structure-Activity Relationship
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D010080:Oxazoles; C007522:4,5-diphenyl-4-oxazolin-2-one; D051546:Cyclooxygenase 2