Synthesis and structure-activity relationship study of substituted caffeateesters as antinociceptive agents modulating the TREK-1 channel.

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.
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https://hal.archives-ouvertes.fr/hal-00955551
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Submitted on : Tuesday, March 4, 2014 - 4:32:53 PM
Last modification on : Thursday, January 11, 2018 - 6:23:45 AM

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  • HAL Id : hal-00955551, version 1

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Nuno Rodrigues, Khalil Bennis, Delphine Vivier, Vanessa Pereira, Franck C. Chatelain, et al.. Synthesis and structure-activity relationship study of substituted caffeateesters as antinociceptive agents modulating the TREK-1 channel.. European Journal of Medicinal Chemistry, Elsevier, 2014, 75, pp.391-402. ⟨hal-00955551⟩

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