Pyrrolidine-carboxamides and oxadiazoles as potent hNK1 antagonists

Abstract The preparation and structure–activity-relationships of novel pyrrolidine-carboxamides and oxadiazoles are described. Compounds in this series were found to be potent hNK 1 antagonists in vitro and efficacious in vivo with minimal interactions with P 450 liver enzymes. Oxadiazole analog 22 was determined to have excellent hNK 1 binding affinity, functional activity, and a good PD response in vivo.