Design and synthesis of novel RXR-selective modulators with improved pharmacological profile

Bioorg Med Chem Lett. 2003 Nov 17;13(22):4071-5. doi: 10.1016/j.bmcl.2003.08.048.

Abstract

New RXR-selective modulators possessing a 6-fluoro trienoic acid moiety (6Z olefin) or a fluorinated/heterocyclic-substituted benzene core ring, were synthesized in an expedient and selective way. A subset of these compounds was evaluated for their metabolic properties (exposure in IRC male mice) and show a dramatic increase of exposure compared to our reference compound, 3 (LG101506).

MeSH terms

  • Animals
  • Binding, Competitive
  • Cell Line
  • Coumarins / chemical synthesis*
  • Coumarins / pharmacology*
  • Drug Design
  • Kinetics
  • Male
  • Mice
  • Receptors, Retinoic Acid / drug effects
  • Receptors, Retinoic Acid / physiology*
  • Retinoic Acid Receptor alpha
  • Retinoic Acid Receptor gamma
  • Retinoid X Receptors
  • Transcription Factors / drug effects
  • Transcription Factors / physiology*
  • Tretinoin / pharmacokinetics

Substances

  • Coumarins
  • Rara protein, mouse
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptors
  • Transcription Factors
  • retinoic acid receptor beta
  • Tretinoin