Syntheses and structure-activity relationships of novel retinoid X receptor agonists

J Med Chem. 1998 Aug 13;41(17):3245-52. doi: 10.1021/jm980058c.


As part of our studies to develop novel retinoids with increased affinity and selectivity for the retinoid X receptor (RXR) subfamily, we have designed and synthesized a series of (E,E,E)-7-(1,2,3, 4-tetrahydroquinolin-6-yl)-7-alkyl-6-fluoro-3-methylhepta-2, 4, 6-trienoic acid derivatives. These tetrahydroquinolines, generated by introducing a polar N atom into the hydrophobic part of the retinoid skeleton, showed high binding affinity to RXRs. Addition of fluorine at the 6-position of the 2,4,6-trienoic acid moiety afforded compounds which elicit potent and selective transactivation of the RXRs. Compound 14b (ER-35794), which possesses an ethyl substituent at the 7-position and fluorine at the 6-position of the triene moiety, is one of the most potent and selective RXR agonists reported to date.

MeSH terms

  • Animals
  • COS Cells
  • Cell Line
  • Cricetinae
  • Drug Design
  • Humans
  • Kinetics
  • Molecular Structure
  • Nuclear Magnetic Resonance, Biomolecular
  • Quinolones / chemical synthesis*
  • Quinolones / chemistry
  • Quinolones / pharmacology*
  • Receptors, Retinoic Acid / agonists*
  • Receptors, Retinoic Acid / metabolism
  • Recombinant Proteins / agonists
  • Recombinant Proteins / metabolism
  • Retinoid X Receptors
  • Structure-Activity Relationship
  • Transcription Factors / agonists*
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transcriptional Activation
  • Transfection
  • Tretinoin / analogs & derivatives*
  • Tretinoin / chemistry
  • Tretinoin / metabolism*


  • Quinolones
  • Receptors, Retinoic Acid
  • Recombinant Proteins
  • Retinoid X Receptors
  • Transcription Factors
  • Tretinoin