Design, synthesis, and structure-activity relationship of a novel series of GluN2C-selective potentiators.
J Med Chem
; 57(6): 2334-56, 2014 Mar 27.
Article
em En
| MEDLINE
| ID: mdl-24512267
ABSTRACT
NMDA receptors are tetrameric complexes composed of GluN1 and GluN2A-D subunits that mediate a slow Ca(2+)-permeable component of excitatory synaptic transmission. NMDA receptors have been implicated in a wide range of neurological diseases and thus represent an important therapeutic target. We herein describe a novel series of pyrrolidinones that selectively potentiate only NMDA receptors that contain the GluN2C subunit. The most active analogues tested were over 100-fold selective for recombinant GluN2C-containing receptors over GluN2A/B/D-containing NMDA receptors as well as AMPA and kainate receptors. This series represents the first class of allosteric potentiators that are selective for diheteromeric GluN2C-containing NMDA receptors.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Receptores de N-Metil-D-Aspartato
/
Agonistas de Aminoácidos Excitatórios
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Med Chem
Assunto da revista:
QUIMICA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Estados Unidos