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

Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, United States
Journal of Medicinal Chemistry (Impact Factor: 5.48). 12/2007; 50(22):5269-80. DOI: 10.1021/jm070556y
Source: PubMed

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 TRbeta isoform selectivity is highly correlated with the structural composition of these covalent inhibitors.

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