title: Structure-guided design of new indoles as negative allosteric modulators (NAMs) of N-methyl-D-aspartate receptor (NMDAR) containing GluN2B subunit.
abstract: Negative allosteric modulators (NAMs) of GluN2B-containing NMDARs provide pharmacological tools for the treatment of chronic neurodegenerative diseases. Novel NAMs have been designed on the basis of computational studies focused on the 'hit compound' 3. This series of indoles has been tested in competition assay. Compounds 16 and 17 were the most active ligands (IC50 values of 83 nM and 71 nM, respectively) and they showed a potency close to that of reference compounds ifenprodil (1, IC50=47 nM) and 3 (IC50=25 nM). Furthermore, docking studies have been performed for active ligand 16 and the results were in a good agreement with biological data.
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali (CHIBIOFARAM) Università degli Studi di Messina, Viale Annunziata, I-98168 Messina, Italy.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Buemi
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali (CHIBIOFARAM) Università degli Studi di Messina, Viale Annunziata, I-98168 Messina, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: De Luca
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali (CHIBIOFARAM) Università degli Studi di Messina, Viale Annunziata, I-98168 Messina, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferro
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Università Magna Graecia, Viale Europa Località Germaneto, I-88100 Catanzaro, Italy.
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
authors.affiliation: Dipartimento di Medicina Sperimentale e Clinica, Università Magna Graecia, Viale Europa Località Germaneto, I-88100 Catanzaro, Italy.
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
authors.affiliation: Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali (CHIBIOFARAM) Università degli Studi di Messina, Viale Annunziata, I-98168 Messina, Italy. Electronic address: rgitto@unime.it.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gitto
mesh_terms: D000494:Allosteric Regulation / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D018698:Glutamic Acid / Q000737:chemistry / Q000378:metabolism*; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D021122:Protein Subunits / Q000737:chemistry* / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D021122:Protein Subunits; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid
keywords: GluN2B/NMDA; Glutamate; Indoles; Molecular docking; Synthesis