Thyroid receptor ligands. 3. Design and synthesis of 3,5-dihalo-4-alkoxyphenylalkanoic acids as indirect antagonists of the thyroid hormone receptor

J Med Chem. 2005 May 5;48(9):3114-7. doi: 10.1021/jm050004k.


Based on the recently described concept of "indirect antagonism" of nuclear receptors, a series of thyroid hormone receptor (TR) antagonists were prepared, in which the outer ring of a thyromimetic was replaced with alkyl chains of variable length and branch. The results of a binding assay for the human TR and reporter cell assay revealed, within this series, a positive correlation between increasing bulk of the alkyl group and affinity to TRs. Compared with already reported TR antagonists, their affinities are within the same range, thus potentially representing a useful approach to novel and high affinity TR-antagonists.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Crystallography, X-Ray
  • Ethers / chemical synthesis
  • Ethers / chemistry
  • Ethers / pharmacology
  • Genes, Reporter
  • Humans
  • Ligands
  • Models, Molecular
  • Phenols / chemistry
  • Protein Structure, Secondary
  • Radioligand Assay
  • Rats
  • Structure-Activity Relationship
  • Thyroid Hormone Receptors alpha / antagonists & inhibitors*
  • Thyroid Hormone Receptors alpha / chemistry
  • Thyroid Hormone Receptors beta / antagonists & inhibitors*
  • Thyroid Hormone Receptors beta / chemistry


  • Ethers
  • Ligands
  • Phenols
  • Thyroid Hormone Receptors alpha
  • Thyroid Hormone Receptors beta