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

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.

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Bibliographische Detailangaben
Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2011-06, Vol.21 (11), p.3407-3410
Hauptverfasser:	Sams, Anette Graven, Mikkelsen, Gitte Kobberøe, Brodbeck, Robbin M., Pu, Xiaosui, Ritzén, Andreas
Format:	Artikel
Sprache:	eng
Schlagworte:	Allosteric modulator Allosteric Regulation Biological and medical sciences chemistry chemotypes Drug Design Efficacy switching Glutamate Glutamatergic system (aspartate and other excitatory aminoacids) glutamic acid Inhibitory Concentration 50 Ligands Medical sciences mGluR5 Molecular Structure NAM Neuropharmacology Neurotransmitters. Neurotransmission. Receptors PAM Pharmacology. Drug treatments 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
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Beschreibung
Zusammenfassung:	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.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2011.03.103