XB-ART-49828
Eur J Med Chem
2014 Mar 21;75:391-402. doi: 10.1016/j.ejmech.2014.01.049.
Show Gene links
Show Anatomy links
Synthesis and structure-activity relationship study of substituted caffeate esters as antinociceptive agents modulating the TREK-1 channel.
???displayArticle.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.
???displayArticle.pubmedLink??? 24561669
???displayArticle.link??? Eur J Med Chem
Species referenced: Xenopus
Genes referenced: kcnk2