Retinoic acid receptor beta,gamma-selective ligands: synthesis and biological activity of 6-substituted 2-naphthoic acid retinoids

J Med Chem. 1996 Jun 7;39(12):2411-21. doi: 10.1021/jm9502293.

Abstract

In search for retinoic acid receptor (RAR) selective ligands, a series of 6-substituted 2-naphthoic acid retinoids were synthesized and evaluated in vitro in a transactivation assay and a competition binding assay for all RARs. These derivatives, in general, showed RAR beta,gamma selectivity. Among these naphthoic acids, oxime derivative 12 was identified as a potent RAR gamma-selective retinoid, while olefinic derivative 11 was found to be comparable to retinoic acid and slightly RAR beta,gamma selective. For the bioassays, a general correlation was observed between the binding affinity of the ligand to the receptors and the potency of the compounds in the transactivation assay. The structure-activity relationship of these naphthoic acids will be discussed.

Publication types

  • Comparative Study

MeSH terms

  • Binding, Competitive
  • Drug Design
  • Genes, Reporter
  • HeLa Cells / drug effects
  • Humans
  • Ligands
  • Molecular Structure
  • Naphthalenes / chemistry*
  • Receptors, Retinoic Acid / drug effects*
  • Receptors, Retinoic Acid / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Retinoic Acid Receptor gamma
  • Retinoids / chemical synthesis
  • Retinoids / metabolism
  • Retinoids / pharmacology*
  • Structure-Activity Relationship
  • Substrate Specificity
  • Transcriptional Activation / drug effects
  • Tretinoin / metabolism

Substances

  • Ligands
  • Naphthalenes
  • Receptors, Retinoic Acid
  • Recombinant Fusion Proteins
  • Retinoids
  • retinoic acid receptor beta
  • Tretinoin
  • 2-naphthoic acid