Efficient synthesis of novel glutamate homologues and investigation of their affinity and selectivity profile at ionotropic glutamate receptors

A convenient synthesis of four new enantiomerically pure acidic amino acids is reported and their affinity at ionotropic glutamate receptors was determined. The new compounds are higher homologues of glutamic acid in which the molecular complexity has been increased by introducing an aromatic/hetero...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2014-04, Vol.24 (8), p.1980-1982
Main Authors: Pinto, Andrea, Tamborini, Lucia, Mastronardi, Federica, Ettari, Roberta, Romano, Diego, Nielsen, Birgitte, De Micheli, Carlo, Conti, Paola
Format: Article
Language:English
Subjects:
Animals
Binding Sites
Chemistry Techniques, Analytical
Glutamic Acid - chemical synthesis
Glutamic Acid - pharmacology
Inhibitory Concentration 50
Molecular Structure
Protein Binding - drug effects
Rats
Receptors, Ionotropic Glutamate - agonists
Stereoisomerism
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Summary:A convenient synthesis of four new enantiomerically pure acidic amino acids is reported and their affinity at ionotropic glutamate receptors was determined. The new compounds are higher homologues of glutamic acid in which the molecular complexity has been increased by introducing an aromatic/heteroaromatic ring, that is a phenyl or a thiophene ring, that could give additional electronic interactions with the receptors. The results of the present investigation indicate that the insertion of an aromatic/heteroaromatic ring into the amino acid skeleton of glutamate higher homologues is well tolerated and this modification could be exploited to generate a new class of NMDA antagonists.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2014.02.058