Synthesis and structure-activity relationship study of substituted caffeate esters as antinociceptive agents modulating the TREK-1 channel.
Eur J Med Chem
; 75: 391-402, 2014 Mar 21.
Article
en En
| MEDLINE
| ID: mdl-24561669
ABSTRACT
The TWIK-related K(+) channel, TREK-1, has recently emerged as an attractive therapeutic target for the development of a novel class of analgesic drugs. It has been reported that TREK-1 -/- mice were more sensitive than wild-type mice to painful stimuli, suggesting that activation of TREK-1 could result in pain inhibition. Here we report the synthesis of a series of substituted caffeate esters (12a-u) based on the hit compound CDC 2 (cinnamyl 3,4-dihydroxyl-α-cyanocinnamate). These analogs were evaluated for their ability to modulate TREK-1 channel by electrophysiology and for their in vivo antinociceptive activity (acetic acid induced-writhing assay) leading to the identification a series of novel molecules able to activate TREK-1 and displaying potent analgesic activity in vivo.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dolor
/
Ácidos Cafeicos
/
Canales de Potasio de Dominio Poro en Tándem
/
Analgésicos
Límite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Año:
2014
Tipo del documento:
Article
País de afiliación:
Francia