5-heteroatom substituted pyrazoles as canine COX-2 inhibitors. Part 1: Structure-activity relationship studies of 5-alkylamino pyrazoles and discovery of a potent, selective, and orally active analog.
Structure-activity relationship (SAR) studies of the novel 2-[3-di and trifluoromethyl-5-alkylamino pyrazo-1-yl]-5-methanesulfonyl (SO(2)Me)/sulfamoyl (SO(2)NH(2))-pyridine derivatives for canine COX enzymes are described. The studies led to the identification of 2e as lead with potent in vitro activity, selectivity, and in vivo activity in dogs and cats.
Sakya
Subas M
SM
Veterinary Medicine Research and Development Pfizer Inc., Groton, CT 06340, USA. subas.m.sakya@pfizer.com
DeMello
Kristin M Lundy
KM
Minich
Martha L
ML
Rast
Bryson
B
Shavnya
Andrei
A
Rafka
Robert J
RJ
Koss
David A
DA
Cheng
Hengmiao
H
Li
Jin
J
Jaynes
Burton H
BH
Ziegler
Carl B
CB
Mann
Donald W
DW
Petras
Carol F
CF
Seibel
Scott B
SB
Silvia
Annette M
AM
George
David M
DM
Lund
Lisa A
LA
St Denis
Suzanne
S
Hickman
Anne
A
Haven
Michelle L
ML
Lynch
Michael P
MP
D000284:Administration, Oral; D000818:Animals; D002415:Cats; D051546:Cyclooxygenase 2 / Q000187:drug effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D066298:In Vitro Techniques; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship
C508197:3-difluoromethyl-5-(cis-2,6-dimethylmorpholin-4-yl)-1-(5-methanesulfonyl-pyridin-2-yl)-1H-pyrazole-4-carbonitrile; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D051546:Cyclooxygenase 2