title: Comparative structure-activity relationship studies of 1-(5-methylsulfonylpyrid-2-yl)-5-alkyl and (hetero)aryl triazoles and pyrazoles in canine COX inhibition.
abstract: 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.
authors.affiliation: Veterinary Medicine Research and Development Pfizer Inc, Groton, CT 06340, USA. subas.m.sakya@pfizer.com
authors.forename: Subas M
authors.initials: SM
authors.lastname: Sakya
authors.forename: Andrei
authors.initials: A
authors.lastname: Shavnya
authors.forename: Hengmiao
authors.initials: H
authors.lastname: Cheng
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.forename: Bryson
authors.initials: B
authors.lastname: Rast
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: David A
authors.initials: DA
authors.lastname: Koss
authors.forename: Burton H
authors.initials: BH
authors.lastname: Jaynes
authors.forename: Donald W
authors.initials: DW
authors.lastname: Mann
authors.forename: Carol F
authors.initials: CF
authors.lastname: Petras
authors.forename: Scott B
authors.initials: SB
authors.lastname: Seibel
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Haven
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lynch
mesh_terms: 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*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D004987:Ethers; D011720:Pyrazoles; D013438:Sulfhydryl Compounds; D014230:Triazoles; D051546:Cyclooxygenase 2