The neuronal calcium ion channel activity of constrained analogues of MONIRO-1.
Bioorg Med Chem
; 28(18): 115655, 2020 09 15.
Article
en En
| MEDLINE
| ID: mdl-32828422
ABSTRACT
Structural modifications of the neuronal calcium channel blocker MONIRO-1, including constraining the phenoxyaniline portion of the molecule and replacing the guanidinium functionality with tertiary amines, led to compounds with significantly improved affinities for the endogenously expressed CaV2.2 channel in the SH-SY5Y neuroblastoma cell line. These analogues also showed promising activity towards the CaV3.2 channel, recombinantly expressed in HEK293T cells. Both of these ion channels have received attention as likely targets for the treatment of neuropathic pain. The dibenzoazepine and dihydrobenzodiazepine derivatives prepared in this study show an encouraging combination of neuronal calcium ion channel inhibitory potency, plasma stability and potential to cross the blood-brain-barrier.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Benzodiazepinas
/
Proteínas Recombinantes
/
Bloqueadores de los Canales de Calcio
/
Canales de Calcio
/
Anilidas
/
Neuralgia
/
Antineoplásicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Australia