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

Structure–activity relationship (SAR) studies of the novel 2-[3-di and trifluoromethyl-5-alkylamino pyrazo-1-yl]-5-methanesulfonyl (SO2Me)/sulfamoyl (SO2NH2)-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.

Graphical abstractStructure–activity relationship studies of the novel 2-[3-di and trifluoromethyl-5-alkylamino pyrazo-1-lyl]-5-methanesulfonyl (SO2Me)/5-sulfamoyl (SO2NH2)-pyridine derivatives for canine COX enzymes led to 2e as the lead with desired in vitro activity, selectivity for canine and feline COX-2 enzyme and in vivo efficacy.Figure optionsDownload full-size imageDownload as PowerPoint slide