Carcache, David, Vranesic, Ivan-Toma, Blanz, Joachim, Desrayaud, Sandrine, Fendt, Markus and Glatthar, Ralf (2011) Benzimidazoles as potent and orally active mGlu5 receptor antagonists with an improved PK profile. ACS Medicinal Chemistry Letters, 2 (1). pp. 58-62. ISSN 1948-5875

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.

Item Type:	Article
Related URLs:	Publisher http://pubs.acs.org/journal/amclct
Additional Information:	archiving not formally supported by this publisher
Keywords:	mGlu5; benzimidazoles; pharmacokinetics
Related URLs:	Publisher http://pubs.acs.org/journal/amclct
Date Deposited:	13 Oct 2015 13:16
Last Modified:	13 Oct 2015 13:16
URI:	https://oak.novartis.com/id/eprint/3352