title: Synthesis and biological characterization of 3-substituted 1H-indoles as ligands of GluN2B-containing N-methyl-D-aspartate receptors. Part 2.
abstract: In the course of the identification of new indole derivatives targeting GluN2B-subunit-containing N-methyl-D-aspartate (NMDA) receptor, the (N-1H-indol-6-methanesulfonamide-3-yl)-2-(4-benzylpiperidin-1-yl)ethanone (10b) was identified as a potent ligand for this NMDA receptor subunit. It displays very high binding affinity (IC50 of 8.9 nmol) for displacement of [3H]ifenprodil, thus showing improved potency with respect to the previously reported analogues as confirmed by functional assay. This finding was consistent with the docking pose of compound 10b within the binding pocket localized in the GluN1-GluN2B subunit interface of NMDA receptor tetraheteromeric complex.
authors.affiliation: Dipartimento di Scienze del Farmaco e Prodotti per la Salute, Università di Messina, Viale Annunziata, I-98168 Messina, Italy. rgitto@unime.it
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gitto
authors.forename: Laura
authors.initials: L
authors.lastname: De Luca
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferro
authors.forename: Maria R
authors.initials: MR
authors.lastname: Buemi
authors.forename: Emilio
authors.initials: E
authors.lastname: Russo
authors.forename: Giovambattista
authors.initials: G
authors.lastname: De Sarro
authors.forename: Mariangela
authors.initials: M
authors.lastname: Chisari
authors.forename: Lucia
authors.initials: L
authors.lastname: Ciranna
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
mesh_terms: D000818:Animals; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008958:Models, Molecular; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000187:drug effects*; D014961:X-Ray Diffraction
chemical_list: D007211:Indoles; D008024:Ligands; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate