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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

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

Carcache David D Vranesic Ivo I Blanz Joachim J Desrayaud Sandrine S Fendt Markus M Glatthar Ralf R

ACS medicinal chemistry letters 20101102 1

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. ...[more]

PMID: 24900255

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