Synthesis and structure-activity relationship study of substituted caffeate esters as antinociceptive agents modulating the TREK-1 channel.
Basic Information
ID: ALA3124774
Journal: Eur J Med Chem
Title: Synthesis and structure-activity relationship study of substituted caffeate esters as antinociceptive agents modulating the TREK-1 channel.
Authors: Rodrigues N, Bennis K, Vivier D, Pereira V, C Chatelain F, Chapuy E, Deokar H, Busserolles J, Lesage F, Eschalier A, Ducki S.
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.
CiteXplore: 24561669
DOI: 10.1016/j.ejmech.2014.01.049
Patent ID: ┄