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.
|Number of pages||12|
|Journal||Journal of Medicinal Chemistry|
|State||Published - Nov 1 2007|
ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery