Literature DB >> 23727046

N-Acyl-N'-arylpiperazines as negative allosteric modulators of mGlu1: identification of VU0469650, a potent and selective tool compound with CNS exposure in rats.

Kimberly M Lovell1, Andrew S Felts, Alice L Rodriguez, Daryl F Venable, Hyekyung P Cho, Ryan D Morrison, Frank W Byers, J Scott Daniels, Colleen M Niswender, P Jeffrey Conn, Craig W Lindsley, Kyle A Emmitte.   

Abstract

Development of SAR in an N-acyl-N'-arylpiperazine series of negative allosteric modulators of mGlu1 using a functional cell-based assay is described in this Letter. Characterization of selected compounds in protein binding assays was used to aid in selecting VU0469650 for further profiling in ancillary pharmacology assays and pharmacokinetic studies. VU0469650 demonstrated an excellent selectivity profile and good exposure in both plasma and brain samples following intraperitoneal dosing in rats.
Copyright © 2013 Elsevier Ltd. All rights reserved.

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Year:  2013        PMID： 23727046      PMCID： PMC3875306          DOI： 10.1016/j.bmcl.2013.05.020

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


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