Synthesis and characterization of 1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives: Part 3. New potent non-competitive metabotropic glutamate receptor 2/3 antagonists.
Bioorg Med Chem Lett
; 18(8): 2725-9, 2008 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-18374569
ABSTRACT
A series of 1,3-dihydro-benzo[b][1,4]diazepin-2-one derivatives was evaluated as non-competitive mGluR2/3 antagonists. Replacement of the (2-aryl)-ethynyl-moiety in 8-position with smaller less lipophilic substituents produced compounds inhibiting the binding of [3H]-LY354740 to rat mGluR2 with low nanomolar affinity and consistent functional effect at both mGluR2 and mGluR3. These compounds were able to reverse LY354740-mediated inhibition of field excitatory postsynaptic potentials in the rat dentate gyrus and in vivo activity could be demonstrated by reversal of the LY354740-induced hypoactivity in mice after oral administration.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzodiazepinas
/
Receptores de Glutamato Metabotrópico
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article