Synthesis and SAR of heteroaryl-phenyl-substituted pyrazole derivatives as highly selective and potent canine COX-2 inhibitors.
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.
Cheng
Hengmiao
H
Veterinary Medicine Research and Development Pfizer Inc., Groton, CT 06340, USA. henry.cheng@pfizer.com
Lundy DeMello
Kristin M
KM
Li
Jin
J
Sakya
Subas M
SM
Ando
Kazuo
K
Kawamura
K
K
Kato
Tomoki
T
Rafka
Robert J
RJ
Jaynes
Burton H
BH
Ziegler
Carl B
CB
Stevens
Rod
R
Lund
Lisa A
LA
Mann
Donald W
DW
Kilroy
Carolyn
C
Haven
Michelle L
ML
Nimz
Erik L
EL
Dutra
Jason K
JK
Li
Chao
C
Minich
Martha L
ML
Kolosko
Nicole L
NL
Petras
Carol
C
Silvia
Annette M
AM
Seibel
Scott B
SB
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
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2