Referenced in: none

Automatically associated channels: TREK1

Title: Synthesis and structure-activity relationship study of substituted caffeate esters as antinociceptive agents modulating the TREK-1 channel.

Authors: Nuno Rodrigues, Khalil Bennis, Delphine Vivier, Vanessa Pereira, Franck C Chatelain, Eric Chapuy, Hemantkumar Deokar, Jérome Busserolles, Florian Lesage, Alain Eschalier, Sylvie Ducki

Journal, date & volume: Eur J Med Chem, 2014 Mar 21 , 75, 391-402

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/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.