Synthesis and SAR of a novel metabotropic glutamate receptor 4 (mGlu4) antagonist: unexpected 'molecular switch' from a closely related mGlu4 positive allosteric modulator.

Utley T, Haddenham D, Salovich JM, Zamorano R, Vinson PN, Lindsley CW, Hopkins CR, Niswender CM
Bioorg Med Chem Lett. 2011 21 (23): 6955-9

PMID: 22030026 · PMCID: PMC3319082 · DOI:10.1016/j.bmcl.2011.09.131

Herein we report the discovery and SAR of a novel antagonist of metabotropic glutamate receptor 4 (mGlu(4)). The antagonist was discovered via a molecular switch from a closely related mGlu(4) positive allosteric modulator (PAM). This antagonist (VU0448383) displays an IC(50) value of 8.2±0.4 μM and inhibits an EC(80) glutamate response by 63.1±6.6%.

Copyright © 2011 Elsevier Ltd. All rights reserved.

MeSH Terms (11)

Allosteric Regulation Animals Cells, Cultured Drug Design Humans Inhibitory Concentration 50 Molecular Structure Pyridines Rats Receptors, Metabotropic Glutamate Structure-Activity Relationship

Connections (1)

This publication is referenced by other Labnodes entities: