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

doi:10.1021/jm070556y

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 journal › Article › peer-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 language	English
Pages (from-to)	5269-5280
Number of pages	12
Journal	Journal of Medicinal Chemistry
Volume	50
Issue number	22
DOIs	https://doi.org/10.1021/jm070556y
State	Published - Nov 1 2007

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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AU - Fletterick, Robert J.

AU - Guy, R. Kiplin

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

Abstract

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