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.
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.
Li
Jin
J
Pfizer Inc, Groton, CT 06340, USA. jin_li@groton.pfizer.com
Lynch
Michael P
MP
Demello
Kristin Lundy
KL
Sakya
Subas M
SM
Cheng
Hengmiao
H
Rafka
Robert J
RJ
Bronk
Brian S
BS
Jaynes
Burton H
BH
Kilroy
Carolyn
C
Mann
Donald W
DW
Haven
Michelle L
ML
Kolosko
Nicole L
NL
Petras
Carol
C
Seibel
Scott B
SB
Lund
Lisa A
LA
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*
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