5-Heteroatom-substituted pyrazoles as canine COX-2 inhibitors: Part 2. Structure-activity relationship studies of 5-alkylethers and 5-thioethers.
Structure-activity relationship (SAR) studies of novel 2-[3-trifluoromethyl-5-alkyl(thio)ether pyrazo-1-yl]-5-methanesulfonyl pyridine derivatives for canine COX enzymes are described. The 4-cyano-5-alkyl ethers were found to have excellent potency and selectivity, whereas the 5-thioethers were potent but less selective than the ether analogs in a canine whole blood (CWB) COX-2 assay.
Sakya
Subas M
SM
Veterinary Medicine Research and Development, Pfizer Inc., Groton, CT 06340, USA. subas.m.sakya@pfizer.com
Cheng
Hengmiao
H
Lundy Demello
Kristin M
KM
Shavnya
Andrei
A
Minich
Martha L
ML
Rast
Bryson
B
Dutra
Jason
J
Li
Chao
C
Rafka
Robert J
RJ
Koss
David A
DA
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
Hickman
Anne
A
Haven
Michelle L
ML
Lynch
Michael P
MP
D000478:Alkylation; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D004285:Dogs; D004987:Ethers / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011720:Pyrazoles / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D052246:Cyclooxygenase 2 Inhibitors; D004987:Ethers; D011720:Pyrazoles; D013438:Sulfhydryl Compounds; D051546:Cyclooxygenase 2