title: In vitro and in vivo profile of 2-(3-di-fluoromethyl-5-phenylpyrazol-1-yl)-5-methanesulfonylpyridine, a potent, selective, and orally active canine COX-2 inhibitor.
abstract: The synthesis of a novel canine COX-2 selective inhibitor, 2-(3-difluoromethyl-5-phenylpyrazol-1-yl)-5-methanesulfonylpyridine, and its in vitro and in vivo profile are described. Pyrazole 8 demonstrated excellent potency and selectivity for canine COX-2 in both in vitro and ex vivo whole blood assays. This novel COX-2 inhibitor also showed a good pharmacokinetic profile (pk) following oral (po), intravenous (iv), and subcutaneous (sc) dosing and demonstrated excellent in vivo efficacy in a canine synovitis model.
authors.affiliation: Pfizer Inc, Groton, CT 06340, USA. jin_li@groton.pfizer.com
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lynch
authors.forename: Kristin Lundy
authors.initials: KL
authors.lastname: Demello
authors.forename: Subas M
authors.initials: SM
authors.lastname: Sakya
authors.forename: Hengmiao
authors.initials: H
authors.lastname: Cheng
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Rafka
authors.forename: Brian S
authors.initials: BS
authors.lastname: Bronk
authors.forename: Burton H
authors.initials: BH
authors.lastname: Jaynes
authors.forename: Carolyn
authors.initials: C
authors.lastname: Kilroy
authors.forename: Donald W
authors.initials: DW
authors.lastname: Mann
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Haven
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Kolosko
authors.forename: Carol
authors.initials: C
authors.lastname: Petras
authors.forename: Scott B
authors.initials: SB
authors.lastname: Seibel
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lund
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004285:Dogs; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: C502256:2-(3-di-fluoromethyl-5-phenylpyrazol-1-yl)-5-methanesulfonylpyridine; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases