N-Acyl-N'-arylpiperazines As Negative Allosteric Modulators of MGlu1: Identification of VU0469650, a Potent and Selective Tool Compound with CNS Exposure in Rats

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2013 Jun 4

PMID 23727046

Citations 8

Authors

Kimberly M Lovell

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

Affiliations

Soon will be listed here.

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.

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