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