Discovery of a potent, selective and orally active canine COX-2 inhibitor, 2-(3-difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine

…, KML DeMello, H Cheng, SM Sakya, BS Bronk…

Index: Li, Jin; Lundy DeMello, Kristin M.; Cheng, Henry; Sakya, Subas M.; Bronk, Brian S.; Rafka, Robert J.; Jaynes, Burton H.; Ziegler, Carl B.; Kilroy, Carolyn; Mann, Donald W.; Nimz, Eric L.; Lynch, Michael P.; Haven, Michelle L.; Kolosko, Nicole L.; Minich, Martha L.; Li, Chao; Dutra, Jason K.; Rast, Bryson; Crosson, Rhonda M.; Morton, Barry J.; Kirk, Glen W.; Callaghan, Kathleen M.; Koss, David A.; Shavnya, Andrei; Lund, Lisa A.; Seibel, Scott B.; Petras, Carol F.; Silvia, Annette Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 1 p. 95 - 98

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Citation Number: 38

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.