Abstract
We previously developed carborane-containing potent AR antagonists, BA321 and BA341, on the basis of our hypothesis that the carborane cage would be an excellent hydrophobic pharmacophore in place of steroidal C and D rings. As an extension of that work, we designed and synthesized carborane-containing AR antagonist candidates with a pyridine ring. Compound 6b, which has a pyridine ring directly bound to the p-carborane cage at the 3-position, exhibited potent AR-antagonistic activity in transcriptional activation assay using NIH3T3 cells transfected with a hAR-expression plasmid. In addition, it showed more potent antiandrogenic activity than that of the well-known antiandrogen flutamide and comparable activity to that of (R)-bicalutamide in SC-3 cell proliferation assay.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Androgen Antagonists / chemical synthesis*
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Androgen Antagonists / chemistry
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Androgen Antagonists / pharmacology*
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Androgen Receptor Antagonists*
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Anilides / pharmacology
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Animals
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Binding, Competitive
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Boranes / chemical synthesis*
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Boranes / chemistry
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Boranes / pharmacology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Drug Design
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Drug Evaluation, Preclinical
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Flutamide / chemistry
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Flutamide / pharmacology
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Humans
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Hydrophobic and Hydrophilic Interactions
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Mice
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Molecular Structure
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NIH 3T3 Cells
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Nitriles / pharmacology
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Pyridines / chemistry*
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Receptors, Androgen / chemistry
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Stereoisomerism
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Structure-Activity Relationship
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Tosyl Compounds / pharmacology
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Transfection
Substances
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AR protein, human
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Androgen Antagonists
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Androgen Receptor Antagonists
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Anilides
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Boranes
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Nitriles
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Pyridines
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Receptors, Androgen
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Tosyl Compounds
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Flutamide
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bicalutamide
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pyridine