Design and synthesis of novel 3-hydroxy-cyclobut-3-ene-1,2-dione derivatives as thyroid hormone receptor beta (TR-beta) selective ligands

Bioorg Med Chem Lett. 2008 Jul 15;18(14):3919-24. doi: 10.1016/j.bmcl.2008.06.038. Epub 2008 Jun 14.

Abstract

Design and synthesis of a novel 3-hydroxy-cyclobut-3-ene-1,2-dione derivatives are reported and their in vitro thyroid hormone receptor selectivity has been evaluated in the thyroid luciferase receptor assay. The 3-[3,5-dichloro-4-(4-hydroxy-3-isopropylphenoxy)-phenylamino]-4-hydroxy-cyclobut-3-ene-1,2-dione 21 has shown selectivity towards thyroid hormone receptor beta.

MeSH terms

  • Chemistry, Pharmaceutical / methods
  • Crystallography, X-Ray
  • Cyclobutanes / chemistry*
  • Drug Design
  • Humans
  • Ligands
  • Luciferases / metabolism
  • Models, Chemical
  • Molecular Conformation
  • Phenyl Ethers / pharmacology
  • Phenylacetates / pharmacology
  • Protein Binding
  • Structure-Activity Relationship
  • Thyroid Gland / enzymology
  • Thyroid Hormone Receptors alpha / metabolism
  • Thyroid Hormone Receptors beta / chemistry*
  • Thyroid Hormone Receptors beta / metabolism*

Substances

  • 3-cyclobutene-1,2-dione
  • Cyclobutanes
  • KB 141
  • Ligands
  • Phenyl Ethers
  • Phenylacetates
  • Thyroid Hormone Receptors alpha
  • Thyroid Hormone Receptors beta
  • Luciferases