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

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.

SUBMITTER: Arnold LA

PROVIDER: S-EPMC2536611 | biostudies-literature | 2007 Nov

REPOSITORIES: biostudies-literature

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

Arnold Leggy A LA Kosinski Aaron A Estébanez-Perpiñá Eva E Fletterick Robert J RJ Guy R Kiplin RK

Journal of medicinal chemistry 20071005 22

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 selec ...[more]

PMID: 17918822

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