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

Article abstract of DOI:10.1016/S0960-894X(97)10013-0

We recently described the synthesis and characterization of MDL 105,212, a non peptide tachykinin antagonist with high affinity for NK₁ and NK₂ receptors. Here we report the synthesis and structure-activity relationships for a series of analogs of MDL 105,212 with regards to: NK₁ and NK₂ 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.