Synthesis and pharmacological characterization of constrained analogues of Vestipitant as in vitro potent and orally active NK1 receptor antagonists

A focused exploration targeting conformationally restricted analogues of Vestipitant, resulted in the discovery of novel, in vitro potent NK 1 antagonists. In particular, two of the compounds reported exhibited a good pharmacokinetic (PK) profile and produced anxiolytic-like effects in the gerbil foot tapping (GFT) in vivo model.