Benzimidazoles as Potent and Orally Active mGlu5 Receptor Antagonists with an Improved PK Profile.

ABSTRACT: A focused chemical optimization effort of compound 1 based on metabolite elucidation is described, resulting in 15i, a highly potent and selective mGlu5 receptor antagonist with an improved pharmacokinetic profile compared to 1. Characterization of 15i in vivo in the fear-potentiated startle (FPS) paradigm revealed a robust reduction of conditioned fear behavior. This effect nicely correlates with the rat brain pharmacokinetics.

SUBMITTER: Carcache D 

PROVIDER: S-EPMC4018045 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature