title: Discovery of a potent, selective and orally active canine COX-2 inhibitor, 2-(3-difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine.
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.
authors.affiliation: Veterinary Medicine Research and Development, Pfizer Inc., Groton, CT 06340, USA. jin_li@groton.pfizer.com
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Kristin M Lundy
authors.initials: KM
authors.lastname: DeMello
authors.forename: Henry
authors.initials: H
authors.lastname: Cheng
authors.forename: Subas M
authors.initials: SM
authors.lastname: Sakya
authors.forename: Brian S
authors.initials: BS
authors.lastname: Bronk
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Rafka
authors.forename: Burton H
authors.initials: BH
authors.lastname: Jaynes
authors.forename: Carl B
authors.initials: CB
authors.lastname: Ziegler
authors.forename: Carolyn
authors.initials: C
authors.lastname: Kilroy
authors.forename: Donald W
authors.initials: DW
authors.lastname: Mann
authors.forename: Eric L
authors.initials: EL
authors.lastname: Nimz
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lynch
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Haven
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Kolosko
authors.forename: Martha L
authors.initials: ML
authors.lastname: Minich
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.forename: Jason K
authors.initials: JK
authors.lastname: Dutra
authors.forename: Bryson
authors.initials: B
authors.lastname: Rast
authors.forename: Rhonda M
authors.initials: RM
authors.lastname: Crosson
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Morton
authors.forename: Glen W
authors.initials: GW
authors.lastname: Kirk
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Callaghan
authors.forename: David A
authors.initials: DA
authors.lastname: Koss
authors.forename: Andrei
authors.initials: A
authors.lastname: Shavnya
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lund
authors.forename: Scott B
authors.initials: SB
authors.lastname: Seibel
authors.forename: Carol F
authors.initials: CF
authors.lastname: Petras
authors.forename: Annette
authors.initials: A
authors.lastname: Silvia
mesh_terms: D000284:Administration, Oral; D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry*; D004285:Dogs; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage* / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011725:Pyridines; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases