Inhibitors of the interaction of a thyroid hormone receptor and coactivators: Preliminary structure-activity relationships

Leggy A. Arnold, Aaron Kosinski, Eva Estébanez-Perpiñá, Robert J. Fletterick, R. Kiplin Guy

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

The modulation of gene regulation by blocking the interaction between the thyroid receptor (TR) and obligate coregulators has been reported recently with the discovery of the lead compound 3-(dimethylamino)-1-(4-hexylphenyl)propan-1- one). Herein we report studies aimed at optimization of this initial hit to determine the basic parameters of the structure-activity relationships and clarify the mechanism of action. These studies provided new insights, showing that activity and TRβ isoform selectivity is highly correlated with the structural composition of these covalent inhibitors.

Original languageEnglish
Pages (from-to)5269-5280
Number of pages12
JournalJournal of Medicinal Chemistry
Volume50
Issue number22
DOIs
StatePublished - Nov 1 2007

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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