Abstract
A novel series of N-arylpiperazine-1-carboxamide derivatives was synthesized and their androgen receptor (AR) antagonist activities and in vivo antiandrogenic properties were evaluated. Reporter assays indicated that trans-2,5-dimethylpiperazine derivatives are potent AR antagonists, and in this series trans-N-4-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2,4-difluorophenyl)-2,5-dimethylpiperazine-1-carboxamide (18 g, YM-175735) exhibited the most potent antiandrogenic activity. Compared to bicalutamide, YM-175735 is an approximately 4-fold stronger AR antagonist and has slightly increased antiandrogenic activity, suggesting that YM-175735 may be useful in the treatment of prostate cancer.
MeSH terms
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Aminoimidazole Carboxamide / chemical synthesis*
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Aminoimidazole Carboxamide / pharmacology*
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Androgen Antagonists / chemical synthesis*
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Androgen Antagonists / pharmacology*
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Androgen Antagonists / therapeutic use
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Androgen Receptor Antagonists*
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Animals
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Indicators and Reagents
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Magnetic Resonance Spectroscopy
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Male
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Mass Spectrometry
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Orchiectomy
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Piperazines / chemical synthesis*
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Piperazines / pharmacology*
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Piperazines / therapeutic use
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Prostate / drug effects
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Prostate / growth & development
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Prostatic Neoplasms / drug therapy
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Rats
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Rats, Wistar
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Testosterone / 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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Piperazines
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Aminoimidazole Carboxamide
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Testosterone