Synthesis and biological properties of new stilbene derivatives of resveratrol as new selective aryl hydrocarbon modulators

  • J Med Chem. 2005 Jan 13;48(1):287-91. doi: 10.1021/jm0498194.
Philippe de Medina  1 ,  Robert Casper ,  Jean-François Savouret ,  Marc Poirot
Affiliations
  • 1. INSERM U 563, Centre de Physiopathologie de Toulouse Purpan, Innovation Thérapeutique et Oncologie Moléculaire, Institut Claudius Regaud, 20-24 rue du Pont Saint Pierre, 31052 Toulouse Cedex, France.
PMID: 15634023 DOI: 10.1021/jm0498194
Abstract

We developed new stilbene derivatives of resveratrol (E)-1-(4'-hydroxyphenyl)-2-(3,5-dihydroxyphenyl)ethene) selective for AhR and devoid of affinity for ER. Among the 24 Stilbenes synthesized, all display a higher affinity than resveratrol for AhR. (E)-1-(4'-Trifluoromethylphenyl)-2-(3,5-ditrifluoromethylphenyl)ethene (4e), (E)-1-(4'-methoxyphenyl)-2-(3,5-dichlorophenyl)ethene (4j), and (E)-1-(4'-chlorophenyl)-2-(3,5-dichlorophenyl)ethene (4b) are selective, high-affinity AhR antagonists with, respective, K(i)s of 2.1, 1.4, and 1.2 nM. (E)-1-(4'-Trifluoromethylphenyl)-2-(3,5-dichlorophenyl)ethene (4i) displays a K(i) of 0.2 nM and is a selective and high-affinity agonist on AhR.

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