title: Recent progress on the identification of metabotropic glutamate 4 receptor ligands and their potential utility as CNS therapeutics.
abstract: This Review describes recent activity in the advancement of ligands for the metabotropic glutamate 4 receptor subtype and their potential utility as central nervous system (CNS) therapeutics. Until recently, there was a paucity of compounds with suitable selectivity and druglike properties to elucidate the value of this target. The search for selective entities has led several groups to the investigation of allosteric modulators as a path to optimization of potential ligands. Recent efforts, discussed here, have afforded a variety of derivatives with improvements in potency, solubility, and pharmacokinetic properties that garner support for continued investigation and optimization.
authors.affiliation: Chemical & Pharmacokinetic Sciences, Lundbeck Research USA, 215 College Road, Paramus, New Jersey 07652, USA. AJR@Lundbeck.com
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Robichaud
authors.forename: Darren W
authors.initials: DW
authors.lastname: Engers
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
authors.forename: Corey R
authors.initials: CR
authors.lastname: Hopkins
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002491:Central Nervous System Agents / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use*; D055808:Drug Discovery / Q000639:trends*; D018698:Glutamic Acid / Q000737:chemistry / Q000378:metabolism / Q000627:therapeutic use; D006801:Humans; D008024:Ligands; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D002491:Central Nervous System Agents; D008024:Ligands; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; C108823:metabotropic glutamate receptor 4