Potent mGluR5 antagonists: pyridyl and thiazolyl-ethynyl-3,5-disubstituted-phenyl series.

Alagille D, DaCosta H, Chen Y, Hemstapat K, Rodriguez A, Baldwin RM, Conn PJ, Conn JP, Tamagnan GD
Bioorg Med Chem Lett. 2011 21 (11): 3243-7

PMID: 21546249 · PMCID: PMC3826776 · DOI:10.1016/j.bmcl.2011.04.047

We report the synthesis of four series of 3,5-disubstituted-phenyl ligands targeting the metabotropic glutamate receptor subtype 5: (2-methylthiazol-4-yl)ethynyl (1a-j,), (6-methylpyridin-2-yl)ethynyl (2a-j), (5-methylpyridin-2-yl)ethynyl (3a-j,), and (pyridin-2-yl)ethynyl (4a-j,). The compounds were evaluated for antagonism of glutamate-mediated mobilization of internal calcium in an mGluR5 in vitro assay. All compounds were found to be full antagonists and exhibited low nanomolar to subnanomolar activity.

Copyright © 2011 Elsevier Ltd. All rights reserved.

MeSH Terms (13)

Acetylene Animals Binding, Competitive Cells, Cultured Ligands Mice Molecular Structure Pyridines Rats Receptor, Metabotropic Glutamate 5 Receptors, Metabotropic Glutamate Structure-Activity Relationship Thiazoles

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