Inhibitors of the Interaction of a Thyroid Hormone Receptor and Coactivators: Preliminary Structure-Activity Relationships

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• 作者：Leggy A. Arnold ; Aaron Kosinski ; Eva Esté ; banez-Perpiñ ; á ; Robert J. Fletterick ; R. Kiplin Guy ; R.K. Guy
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：November 1, 2007
• 年：2007
• 卷：50
• 期：22
• 页码：5269 - 5280
• 全文大小：412K
• 年卷期：v.50,no.22(November 1, 2007)
• ISSN：1520-4804

文摘

The modulation of gene regulation by blocking the interaction between the thyroid receptor (TR) and obligatecoregulators 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 determinethe basic parameters of the structure-activity relationships and clarify the mechanism of action. Thesestudies provided new insights, showing that activity and TR isoform selectivity is highly correlated withthe structural composition of these covalent inhibitors.