RESUMO
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.
Assuntos
Inibidores de Ciclo-Oxigenase 2 , Ciclo-Oxigenase 2/efeitos dos fármacos , Pirazóis , Administração Oral , Animais , Gatos , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacocinética , Modelos Animais de Doenças , Cães , Avaliação Pré-Clínica de Medicamentos , Técnicas In Vitro , Estrutura Molecular , Pirazóis/síntese química , Pirazóis/química , Pirazóis/farmacocinética , Relação Estrutura-AtividadeRESUMO
Structure-activity relationship (SAR) studies of 2-[3-di(and tri)fluoromethyl-5-arylpyrazol-1-yl]-5-methanesulfonylpyridine derivatives for canine COX enzymes are described. This led to the identification of 12a as a lead candidate for further progression. The in vitro and in vivo activity of 12a for the canine COX-2 enzyme as well as its in vivo efficacy and pharmacokinetic properties in dog are highlighted.