Abstract
We previously identified the methylsulfonylnitrobenzoates (MSNBs) that block the interaction of the thyroid hormone receptor with its obligate transcriptional coactivators and prevent thyroid hormone signaling. As part of our lead optimization work we demonstrated that sulfonylnitrophenylthiazoles (SNPTs), which replace the ester linkage of MSNBs with a thiazole, also inhibited coactivator binding to TR. Here we report that replacement of the ester with an amide (methylsulfonylnitrobenzamides, MSNBA) also provides active TR antagonists.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Benzamides / chemical synthesis
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Benzamides / chemistry*
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Benzamides / toxicity
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Cell Survival / drug effects
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Hep G2 Cells
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Humans
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Nuclear Receptor Coactivator 1 / antagonists & inhibitors*
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Nuclear Receptor Coactivator 1 / genetics
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Nuclear Receptor Coactivator 1 / metabolism
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Protein Interaction Maps / drug effects
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Receptors, Thyroid Hormone / antagonists & inhibitors*
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Receptors, Thyroid Hormone / genetics
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Receptors, Thyroid Hormone / metabolism
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Structure-Activity Relationship
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Thiazoles / chemistry
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Transfection
Substances
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Benzamides
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Receptors, Thyroid Hormone
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Thiazoles
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Nuclear Receptor Coactivator 1