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

DÜNDAR Y., Unlu S., BANOĞLU E., Entrena A., Costantino G., Nunez M., ...More

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol.44, no.5, pp.1830-1837, 2009 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 44 Issue: 5
  • Publication Date: 2009
  • Doi Number: 10.1016/j.ejmech.2008.10.039
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1830-1837
  • Keywords: 4,5-Diphenyloxazolone, Cyclooxygenase inhibition, COX-1, COX-2, Docking, CYCLOOXYGENASE-2 COX-2, AMIDE DERIVATIVES, 3,4-DIARYLOXAZOLONES, INDOMETHACIN, ROFECOXIB, DISEASE, SYSTEM, TARGET
  • Gazi University Affiliated: Yes


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 (IC50COX-1 = >100 mu M, IC50COX-2 = 2 mu m) 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. (C) 2008 Elsevier Masson SAS. All rights reserved.