Format

Send to

Choose Destination
Bioorg Med Chem. 2014 Jan 1;22(1):393-7. doi: 10.1016/j.bmc.2013.11.014. Epub 2013 Nov 15.

From NMDA receptor antagonists to discovery of selective σ₂ receptor ligands.

Author information

1
Dipartimento di Scienze del Farmaco e dei Prodotti per la Salute, Università di Messina, Viale Annunziata, I-98168 Messina, Italy. Electronic address: rgitto@unime.it.
2
Dipartimento di Scienze del Farmaco e dei Prodotti per la Salute, Università di Messina, Viale Annunziata, I-98168 Messina, Italy.
3
Dipartimento di Scienze Chimiche, Viale Ferdinando Stagno d'Alcontres, I-98166 Messina, Italy.
4
Dipartimento di Scienze del Farmaco, Università di Catania, Viale Andrea Doria 6, I-95125 Catania, Italy.

Abstract

Following previous studies focused on the search for new molecules targeting GluN2B-containing NMDA, a small series of 1-(1H-indol-3-yl)-2-(4-phenylpiperidin-1-yl)ethanone derivatives has been synthesized by using Microwave Assisted Organic Synthesis (MAOS). Given that GluN2B ligands frequently exert off-target effects we also tested their affinity towards sigma receptors. Binding assay revealed that only the 1-(5-hydroxy-1H-indol-3-yl)-2-(4-phenylpiperidin-1-yl)ethanone (7a) retained GluN2B affinity. Interestingly, the 5-methoxyindoles 5a and 6a were efficient and selective ligands toward σ₂ receptor (Ki values of 10nM and 20 nM, respectively). Thus, in this case the discovery of new σ₂ receptor selective ligands was an unexpected result emerging from the screening of cross-activity against other CNS receptors.

KEYWORDS:

GluN2B/NMDA; Glutamate; Ifenprodil; Indoles; Sigma receptor

PMID:
24290063
DOI:
10.1016/j.bmc.2013.11.014
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center