From NMDA receptor antagonists to discovery of selective σ2 receptor ligands.
Bioorg Med Chem
; 22(1): 393-7, 2014 Jan 01.
Article
en En
| MEDLINE
| ID: mdl-24290063
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Receptores sigma
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Receptores de N-Metil-D-Aspartato
/
Ácido Glutámico
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2014
Tipo del documento:
Article