title: Synthesis and SAR of heteroaryl-phenyl-substituted pyrazole derivatives as highly selective and potent canine COX-2 inhibitors.
abstract: The discovery of heteroaryl-phenyl-substituted pyrazole derivatives as canine selective COX-2 inhibitors is described. Structure-activity relationship (SAR) studies of this class of compounds led to the identification of compound 1 which demonstrated a canine whole blood COX-2 inhibitory IC50 of 12 nM and selectivity ratio of COX-1/COX-2 greater than 4000-fold.
authors.affiliation: Veterinary Medicine Research and Development Pfizer Inc., Groton, CT 06340, USA. henry.cheng@pfizer.com
authors.forename: Hengmiao
authors.initials: H
authors.lastname: Cheng
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Lundy DeMello
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Subas M
authors.initials: SM
authors.lastname: Sakya
authors.forename: Kazuo
authors.initials: K
authors.lastname: Ando
authors.forename: K
authors.initials: K
authors.lastname: Kawamura
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kato
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Rafka
authors.forename: Burton H
authors.initials: BH
authors.lastname: Jaynes
authors.forename: Carl B
authors.initials: CB
authors.lastname: Ziegler
authors.forename: Rod
authors.initials: R
authors.lastname: Stevens
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Lund
authors.forename: Donald W
authors.initials: DW
authors.lastname: Mann
authors.forename: Carolyn
authors.initials: C
authors.lastname: Kilroy
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Haven
authors.forename: Erik L
authors.initials: EL
authors.lastname: Nimz
authors.forename: Jason K
authors.initials: JK
authors.lastname: Dutra
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.forename: Martha L
authors.initials: ML
authors.lastname: Minich
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Kolosko
authors.forename: Carol
authors.initials: C
authors.lastname: Petras
authors.forename: Annette M
authors.initials: AM
authors.lastname: Silvia
authors.forename: Scott B
authors.initials: SB
authors.lastname: Seibel
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D020128:Inhibitory Concentration 50; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2