title: Efficacy switching SAR of mGluR5 allosteric modulators: highly potent positive and negative modulators from one chemotype.
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.
authors.affiliation: Discovery Chemistry and DMPK, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark.
authors.forename: Anette Graven
authors.initials: AG
authors.lastname: Sams
authors.forename: Gitte Kobberøe
authors.initials: GK
authors.lastname: Mikkelsen
authors.forename: Robbin M
authors.initials: RM
authors.lastname: Brodbeck
authors.forename: Xiaosui
authors.initials: X
authors.lastname: Pu
authors.forename: Andreas
authors.initials: A
authors.lastname: Ritzén
mesh_terms: D000494:Allosteric Regulation; D015195:Drug Design; D020128:Inhibitory Concentration 50; D008024:Ligands; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D054852:Small Molecule Libraries / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D054852:Small Molecule Libraries