Synthesis and biological evaluation of 4,5-diphenyloxazolone derivatives on route towards selective COX-2 inhibitors.
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.
Dündar
Yasemin
Y
Department of Medicinal Chemistry, Faculty of Pharmacy, Gazi University, Taç Sk, 06330 Etiler, Ankara, Turkey.
Unlü
Serdar
S
Banoğlu
Erden
E
Entrena
Antonio
A
Costantino
Gabriele
G
Nuñez
Maria-Teresa
MT
Nunez
Maria-Teresa
MT
Labeaga
Luis
L
Ledo
Francisco
F
Sahin
M Fethi
MF
Noyanalpan
Ningur
N
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
D052246:Cyclooxygenase 2 Inhibitors; D010080:Oxazoles; C007522:4,5-diphenyl-4-oxazolin-2-one; D051546:Cyclooxygenase 2