1. Discovery of a potent, selective and orally active canine COX-2 inhibitor, 2-(3-difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine
- Author
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Rhonda M. Crosson, David A. Koss, Michelle L. Haven, Carolyn Rose Kilroy, Martha L. Minich, Robert J. Rafka, Eric L. Nimz, Morton Barry James, Scott B. Seibel, Lisa A. Lund, Carol F. Petras, Kristin M. Lundy DeMello, Chao Li, Annette M. Silvia, Bryson Rast, Kathleen M. Callaghan, Andrei Shavnya, Michael P. Lynch, Subas M. Sakya, Ziegler Carl B, Jin Li, Nicole L. Kolosko, Bronk Brian Scott, Donald W. Mann, Jason K. Dutra, Burton H. Jaynes, Henry Cheng, and Glen W. Kirk
- Subjects
Pyridines ,Stereochemistry ,Clinical Biochemistry ,Administration, Oral ,Pharmaceutical Science ,Biochemistry ,Chemical synthesis ,Sulfone ,Structure-Activity Relationship ,chemistry.chemical_compound ,Dogs ,Oral administration ,In vivo ,Drug Discovery ,Animals ,Cyclooxygenase Inhibitors ,Molecular Biology ,chemistry.chemical_classification ,Cyclooxygenase 2 Inhibitors ,biology ,Chemistry ,Organic Chemistry ,In vitro ,Isoenzymes ,Enzyme ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,Enzyme inhibitor ,biology.protein ,Molecular Medicine ,COX-2 inhibitor - Abstract
Structure-activity relationship (SAR) studies of 2-[3-di(and tri)fluoromethyl-5-arylpyrazol-1-yl]-5-methanesulfonylpyridine derivatives for canine COX enzymes are described. This led to the identification of 12a as a lead candidate for further progression. The in vitro and in vivo activity of 12a for the canine COX-2 enzyme as well as its in vivo efficacy and pharmacokinetic properties in dog are highlighted.
- Published
- 2004
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