title: 4,4-Dimethyl- and diastereomeric 4-hydroxy-4-methyl- (2S)-glutamate analogues display distinct pharmacological profiles at ionotropic glutamate receptors and excitatory amino acid transporters.
abstract: Subtype-selective ligands are of great interest to the scientific community, as they provide a tool for investigating the function of one receptor or transporter subtype when functioning in its native environment. Several 4-substituted (S)-glutamate (Glu) analogues were synthesized, and altogether this approach has provided important insight into the structure-activity relationships (SAR) for ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs), as well as the excitatory amino acid transporters (EAATs). In this work, three 4,4-disubstituted Glu analogues 1-3, which are hybrid structures of important 4-substituted Glu analogues 4-8, were investigated at iGluRs and EAATs. Collectively, their pharmacological profiles add new and valuable information to the SAR for the iGluRs and EAAT1-3.
authors.affiliation: Department of Medicinal Chemistry, University of Copenhagen, Denmark. lebu@farma.ku.dk
authors.forename: Lennart
authors.initials: L
authors.lastname: Bunch
authors.forename: Darryl S
authors.initials: DS
authors.lastname: Pickering
authors.forename: Thierry
authors.initials: T
authors.lastname: Gefflaut
authors.forename: Virginie
authors.initials: V
authors.lastname: Vinatier
authors.forename: Virgil
authors.initials: V
authors.lastname: Helaine
authors.forename: Ahmad
authors.initials: A
authors.lastname: Amir
authors.forename: Birgitte
authors.initials: B
authors.lastname: Nielsen
authors.forename: Anders A
authors.initials: AA
authors.lastname: Jensen
mesh_terms: D026905:Amino Acid Transport Systems / Q000378:metabolism*; D000818:Animals; D018698:Glutamic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008956:Models, Chemical; D008968:Molecular Conformation; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D026905:Amino Acid Transport Systems; D008024:Ligands; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid