Abstract
Based on the concept of 'indirect antagonism' of nuclear receptors, a series of thyroid hormone receptor (TR) antagonists were prepared with improved affinity compared with what was previously described. The results of a binding assay for the human TR and reporter cell assay revealed, within this series, that an m-bromobenzoyl substituent (11f) was optimal in terms of affinity and antagonist activity. Compared with already reported TR antagonists, their affinities are within the same range, thus potentially representing useful approach to novel and high-affinity TR-antagonists.
MeSH terms
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Bromides / chemical synthesis*
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Humans
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Inhibitory Concentration 50
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Kinetics
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Ligands
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Models, Chemical
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Molecular Conformation
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Protein Binding
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Protein Isoforms
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Structure-Activity Relationship
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Thyroid Hormone Receptors alpha / antagonists & inhibitors*
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Thyroid Hormone Receptors alpha / chemistry
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Thyroid Hormone Receptors beta / antagonists & inhibitors*
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Thyroid Hormone Receptors beta / chemistry
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Transcriptional Activation
Substances
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Bromides
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Ligands
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Protein Isoforms
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Thyroid Hormone Receptors alpha
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Thyroid Hormone Receptors beta