title: Efficient synthesis of novel glutamate homologues and investigation of their affinity and selectivity profile at ionotropic glutamate receptors.
abstract: 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.
authors.affiliation: Dipartimento di Scienze Farmaceutiche DISFARM, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy. Electronic address: andrea.pinto@unimi.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Pinto
authors.affiliation: Dipartimento di Scienze Farmaceutiche DISFARM, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Tamborini
authors.affiliation: Dipartimento di Scienze Farmaceutiche DISFARM, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Mastronardi
authors.affiliation: Dipartimento di Scienze Farmaceutiche DISFARM, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Ettari
authors.affiliation: Dipartimento di Scienze per gli Alimenti, la Nutrizione e l'Ambiente (DeFENS), Università degli Studi di Milano, via Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Romano
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen OE, Denmark.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Nielsen
authors.affiliation: Dipartimento di Scienze Farmaceutiche DISFARM, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: De Micheli
authors.affiliation: Dipartimento di Scienze Farmaceutiche DISFARM, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Conti
mesh_terms: D000818:Animals; D001665:Binding Sites; D002623:Chemistry Techniques, Analytical; D018698:Glutamic Acid / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D058468:Receptors, Ionotropic Glutamate / Q000819:agonists*; D013237:Stereoisomerism
chemical_list: D058468:Receptors, Ionotropic Glutamate; D018698:Glutamic Acid
keywords: Heck reaction; N-Methyl-d-aspartate receptor; Semi-preparative chiral HPLC; d-Allylglycine; l-Glutamic acid