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4,4‐Dimethyl‐ and Diastereomeric 4‐Hydroxy‐4‐methyl‐ (2 S )‐Glutamate Analogues Display Distinct Pharmacological Profiles at Ionotropic Glutamate Receptors and Excitatory Amino Acid Transporters
Author(s) -
Bunch Lennart,
Pickering Darryl S.,
Gefflaut Thierry,
Vinatier Virginie,
Helaine Virgil,
Amir Ahmad,
Nielsen Birgitte,
Jensen Anders A.
Publication year - 2009
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200900258
Subject(s) - ionotropic effect , metabotropic glutamate receptor 1 , metabotropic glutamate receptor , metabotropic glutamate receptor 5 , glutamate receptor , chemistry , metabotropic glutamate receptor 2 , transporter , excitatory amino acid transporter , metabotropic receptor , metabotropic glutamate receptor 6 , amino acid , biochemistry , stereochemistry , receptor , gene
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.