Identification and optimisation of a series of tetrahydrobenzotriazoles as metabotropic glutamate receptor 5-selective positive allosteric modulators ...
Basic Information
ID: ALA3734684
Journal: Bioorg Med Chem Lett
Title: Identification and optimisation of a series of tetrahydrobenzotriazoles as metabotropic glutamate receptor 5-selective positive allosteric modulators that improve performance in a preclinical model of cognition.
Authors: Ellard JM, Madin A, Philps O, Hopkin M, Henderson S, Birch L, O'Connor D, Arai T, Takase K, Morgan L, Reynolds D, Talma S, Howley E, Powney B, Payne AH, Hall A, Gartlon JE, Dawson LA, Castro L, Atkinson PJ.
Abstract: Herein we describe a series of tetrahydrobenzotriazoles as novel, potent metabotropic glutamate receptor subtype 5 (mGlu5) positive allosteric modulators (PAMs). Exploration of the SAR surrounding the tetrahydrobenzotriazole core ultimately led to the identification of 29 as a potent mGlu5 PAM with a low maximal glutamate potency fold shift, acceptable in vitro DMPK parameters and in vivo PK profile and efficacy in the rat novel object recognition (NOR) assay. As a result 29 was identified as a suitable compound for progression to in vivo safety evaluation.
CiteXplore: 26531152
DOI: 10.1016/j.bmcl.2015.10.050
Patent ID: ┄