Synthesis and structure-activity relationships for a series of substituted pyrrolidine NK1/NK2 receptor antagonists

Abstract We recently described the synthesis and characterization of MDL 105,212, a non peptide tachykinin antagonist with high affinity for NK 1 and NK 2 receptors. 1 Here we report the synthesis and structure-activity relationships for a series of analogs of MDL 105,212 with regards to: NK 1 and NK 2 receptor binding affinity, physical-chemical characterization; in vitro absorption potential; in vitro metabolic stability; and efficacy in a capsaicin-challenge conscious guinea pig model after oral administration.