Abstract
The 3-(4-cyano-3-trifluoromethylphenyl)-5,5-dimethylthiohydantoin derivatives which have carboxy-terminal side chains were synthesized and their agonistic/antagonistic activities against androgen receptor (AR) measured. Among them, compound 13b showed antagonistic activity (IC50=130 nM) with no agonistic activity even at 10000 nM. This compound exhibited significant metabolic stability and oral antiandrogenic activity (ED50=7 mg/kg).
MeSH terms
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Androgen Antagonists / chemical synthesis*
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Androgen Antagonists / pharmacology*
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Androgen Receptor Antagonists*
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Animals
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Binding, Competitive / drug effects
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CHO Cells
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Cricetinae
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Cricetulus
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Crystallography, X-Ray
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Genes, Reporter / drug effects
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HeLa Cells
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Humans
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Indicators and Reagents
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Male
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Mice
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Mice, Inbred ICR
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Microsomes, Liver / drug effects
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Microsomes, Liver / metabolism
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Models, Molecular
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Seminal Vesicles / drug effects
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Structure-Activity Relationship
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Thiohydantoins / chemical synthesis
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Thiohydantoins / pharmacology
Substances
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Androgen Antagonists
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Androgen Receptor Antagonists
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Indicators and Reagents
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Thiohydantoins