Synthesis and biological evaluation of 4,5-diphenyloxazolone derivatives on route towards selective COX-2 inhibitors

Eur J Med Chem. 2009 May;44(5):1830-7. doi: 10.1016/j.ejmech.2008.10.039. Epub 2008 Nov 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Computer Simulation
  • Cyclooxygenase 2 / blood
  • Cyclooxygenase 2 / drug effects
  • Cyclooxygenase 2 Inhibitors / chemical synthesis*
  • Humans
  • Inhibitory Concentration 50
  • Oxazoles / chemical synthesis*
  • Oxazoles / pharmacology*
  • Protein Binding
  • Structure-Activity Relationship

Substances

  • Cyclooxygenase 2 Inhibitors
  • Oxazoles
  • 4,5-diphenyl-4-oxazolin-2-one
  • Cyclooxygenase 2