title: 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.
abstract: 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.
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: Kristin M Lundy
authors.initials: KM
authors.lastname: DeMello
authors.forename: Martha L
authors.initials: ML
authors.lastname: Minich
authors.forename: Bryson
authors.initials: B
authors.lastname: Rast
authors.forename: Andrei
authors.initials: A
authors.lastname: Shavnya
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Rafka
authors.forename: David A
authors.initials: DA
authors.lastname: Koss
authors.forename: Hengmiao
authors.initials: H
authors.lastname: Cheng
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Burton H
authors.initials: BH
authors.lastname: Jaynes
authors.forename: Carl B
authors.initials: CB
authors.lastname: Ziegler
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: Annette M
authors.initials: AM
authors.lastname: Silvia
authors.forename: David M
authors.initials: DM
authors.lastname: George
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lund
authors.forename: Suzanne
authors.initials: S
authors.lastname: St Denis
authors.forename: Anne
authors.initials: A
authors.lastname: Hickman
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Haven
authors.forename: Michael P
authors.initials: MP
authors.lastname: Lynch
mesh_terms: 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
chemical_list: 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