Comparative structure-activity relationship studies of 1-(5-methylsulfonylpyrid-2-yl)-5-alkyl and (hetero)aryl triazoles and pyrazoles in canine COX inhibition.
Structure-activity relationship (SAR) studies of novel 5-alkyl and 5-aryl/heteroaryl substituted 1,2,4-triazoles are described. The in vitro activity is compared to the pyrazole class of compounds with analogous side chains to delineate the contribution of the triazole ring nitrogen in binding to the active site. Both series are quite potent and selective in the canine whole blood (CWB) COX-2 assay, suggesting the increased binding contribution of the hydrophobic side chains.
Sakya
Subas M
SM
Veterinary Medicine Research and Development Pfizer Inc, Groton, CT 06340, USA. subas.m.sakya@pfizer.com
Shavnya
Andrei
A
Cheng
Hengmiao
H
Li
Chao
C
Rast
Bryson
B
Li
Jin
J
Koss
David A
DA
Jaynes
Burton H
BH
Mann
Donald W
DW
Petras
Carol F
CF
Seibel
Scott B
SB
Haven
Michelle L
ML
Lynch
Michael P
MP
D000478:Alkylation; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D004987:Ethers / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011720:Pyrazoles / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014230:Triazoles / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D052246:Cyclooxygenase 2 Inhibitors; D004987:Ethers; D011720:Pyrazoles; D013438:Sulfhydryl Compounds; D014230:Triazoles; D051546:Cyclooxygenase 2