Synthesis and SAR of heteroaryl-phenyl-substituted pyrazole derivatives as highly selective and potent canine COX-2 inhibitors

H Cheng, KML DeMello, J Li, SM Sakya, K Ando…

Index: Cheng, Hengmiao; Lundy DeMello, Kristin M.; Li, Jin; Sakya, Subas M.; Ando, Kazuo; Kawamura; Kato, Tomoki; Rafka, Robert J.; Jaynes, Burton H.; Ziegler, Carl B.; Stevens, Rod; Lund, Lisa A.; Mann, Donald W.; Kilroy, Carolyn; Haven, Michelle L.; Nimz, Erik L.; Dutra, Jason K.; Li, Chao; Minich, Martha L.; Kolosko, Nicole L.; Petras, Carol; Silvia, Annette M.; Seibel, Scott B. Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 8 p. 2076 - 2080

Full Text: HTML

Citation Number: 38

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 12nM and selectivity ratio of COX-1/COX-2 greater than 4000- fold.