Efficacy switching SAR of mGluR5 allosteric modulators: highly potent positive and negative modulators from one chemotype

Anette Graven Sams; Gitte Kobberøe Mikkelsen; Robbin M Brodbeck; Xiaosui Pu; Andreas Ritzén

doi:10.1016/j.bmcl.2011.03.103

Efficacy switching SAR of mGluR5 allosteric modulators: highly potent positive and negative modulators from one chemotype

Bioorg Med Chem Lett. 2011 Jun 1;21(11):3407-10. doi: 10.1016/j.bmcl.2011.03.103. Epub 2011 Apr 5.

Authors

Anette Graven Sams¹, Gitte Kobberøe Mikkelsen, Robbin M Brodbeck, Xiaosui Pu, Andreas Ritzén

Affiliation

¹ Discovery Chemistry and DMPK, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark.

PMID: 21531137
DOI: 10.1016/j.bmcl.2011.03.103

Abstract

A series of metabotropic glutamate 5 receptor (mGluR5) allosteric ligands with positive, negative or no modulatory efficacy is described. The ability of this series to yield both mGluR5 PAMs and NAMs with single-digit nanomolar potency is unusual, and the underlying SAR is detailed.

MeSH terms

Allosteric Regulation
Drug Design*
Inhibitory Concentration 50
Ligands
Molecular Structure
Protein Binding / drug effects
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate / metabolism*
Small Molecule Libraries / chemical synthesis*
Small Molecule Libraries / chemistry
Small Molecule Libraries / pharmacology
Structure-Activity Relationship

Substances

Ligands
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate
Small Molecule Libraries