Thyroid receptor ligands. 6. A high affinity "direct antagonist" selective for the thyroid hormone receptor

J Med Chem. 2006 Nov 16;49(23):6635-7. doi: 10.1021/jm060521i.

Abstract

A new high-affinity thyroid hormone antagonist 6 with druglike properties was designed and synthesized. The compound behaved as an antagonist in a cell transactivation assay, and in a first in vivo experiment in rats.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Humans
  • Ligands
  • Models, Molecular
  • Phenylpropionates / chemical synthesis*
  • Phenylpropionates / chemistry
  • Phenylpropionates / pharmacology
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Rats
  • Receptors, Thyroid Hormone / antagonists & inhibitors*
  • Thyroid Hormone Receptors alpha / antagonists & inhibitors
  • Thyroid Hormone Receptors beta / antagonists & inhibitors
  • Thyroid Hormone Receptors beta / chemistry
  • Transcriptional Activation / drug effects

Substances

  • 3-(3,5-dibromo-4-(4-hydroxy-3-isopropyl-5-(2-pyridin-4-ylvinyl)phenoxy)phenyl)propionic acid
  • Ligands
  • Phenylpropionates
  • Pyridines
  • Receptors, Thyroid Hormone
  • Thyroid Hormone Receptors alpha
  • Thyroid Hormone Receptors beta