title: Synthesis and biological characterization of 3-substituted-1H-indoles as ligands of GluN2B-containing N-methyl-D-aspartate receptors.
abstract: As an extension of our studies, novel indole derivatives were rationally designed and synthesized as ligands targeted to GluN2B/NMDA receptors. The 2-(4-benzylpiperidin-1-yl)-1-(6-hydroxy-1H-indol-3-yl)ethanone (4i) and 1-(4-benzylpiperidin-1-yl)-2-(6-hydroxy-1H-indol-3-yl)ethane-1,2-dione (6i) showed high binding affinity in [3H]ifenprodil displacement assay. By computational studies, we suggested the hypothetical interactions playing a significant role during the binding process. However, in functional and in vivo studies the most potent compound 4i did not show any activity whereas it displayed relevant affinity toward the σ2 receptor.
authors: Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, I-98168 Messina, Italy. rgitto@unime.it
authors: Rosaria
authors: R
authors: Gitto
authors: Laura
authors: L
authors: De Luca
authors: Stefania
authors: S
authors: Ferro
authors: Maria Rosa
authors: MR
authors: Buemi
authors: Emilio
authors: E
authors: Russo
authors: Giovambattista
authors: G
authors: De Sarro
authors: Lara
authors: L
authors: Costa
authors: Lucia
authors: L
authors: Ciranna
authors: Orazio
authors: O
authors: Prezzavento
authors: Emanuela
authors: E
authors: Arena
authors: Simone
authors: S
authors: Ronsisvalle
authors: Giuseppe
authors: G
authors: Bruno
authors: Alba
authors: A
authors: Chimirri
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D051379:Mice; D008811:Mice, Inbred DBA; D008958:Models, Molecular; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D017465:Receptors, Opioid, delta / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C570546:1-(4-benzylpiperidin-1-yl)-2-(6-hydroxy-1H-indol-3-yl)ethane-1,2-dione; C570545:2-(4-benzylpiperidin-1-yl)-1-(6-hydroxy-1H-indol-3-yl)ethanone; D000927:Anticonvulsants; D007211:Indoles; D008024:Ligands; C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D017465:Receptors, Opioid, delta