3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)(2-pyridyl) phenyl ketone as a potent and orally active cyclooxygenase-2 selective inhibitor: synthesis and biological evaluation.

Abstract

Incorporation of a spacer group between the central scaffold and the aryl ring resulted in a new cyclooxygenase-2 (COX-2) selective inhibitor core structure, 3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)(2-pyridyl) phenyl ketone (20), with COX-2 IC50 = 0.25 microM and COX-1 IC50 = 14 microM (human whole blood assay). Compound 20 was orally active in the rat air pouch model of inflammation, inhibiting white blood cell infiltration and COX-2-derived PG production. Our data support the identification of a novel COX-2 selective inhibitor core structure exemplified by 20.

• Authors: Subhash P Khanapure, Michael E Augustyniak, Richard A Earl, David S Garvey, L Gordon Letts, Allison M Martino, Madhavi G Murty, David J Schwalb, Matthew J Shumway, Andrzej M Trocha, Delano V Young, Irina S Zemtseva, David R Janero
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 48 Issue 11 Pg. 3930-4 (Jun 02 2005) ISSN: 0022-2623 [Print] United States
• PMID: 15916445 (Publication Type: Journal Article)

Chemical References

• 3-(4-(methylsulfonyl)phenyl)-5-(trifluoromethyl)(2-pyridyl) phenyl ketone
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Pyridines
• Sulfones
• Carrageenan
• Cyclooxygenase 2
• Prostaglandin-Endoperoxide Synthases
• Dinoprostone

Topics

• Administration, Oral
• Animals
• Carrageenan
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (chemical synthesis, chemistry, pharmacology)
• Dinoprostone (antagonists & inhibitors, biosynthesis)
• Inflammation (chemically induced, metabolism)
• Male
• Prostaglandin-Endoperoxide Synthases (metabolism)
• Pyridines (chemical synthesis, chemistry, pharmacology)
• Rats
• Rats, Sprague-Dawley
• Sulfones (chemical synthesis, chemistry, pharmacology)