N-Arylpiperazine-1-carboxamide derivatives: a novel series of orally active nonsteroidal androgen receptor antagonists.

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.

• Authors: Isao Kinoyama, Nobuaki Taniguchi, Eiji Kawaminami, Eisuke Nozawa, Hiroshi Koutoku, Takashi Furutani, Masafumi Kudoh, Minoru Okada
• Journal: Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 53 Issue 4 Pg. 402-9 (Apr 2005) ISSN: 0009-2363 [Print] Japan
• PMID: 15802840 (Publication Type: Journal Article)

Chemical References

• Androgen Antagonists
• Androgen Receptor Antagonists
• Indicators and Reagents
• Piperazines
• Aminoimidazole Carboxamide
• Testosterone

Topics

• Aminoimidazole Carboxamide (chemical synthesis, pharmacology)
• Androgen Antagonists (chemical synthesis, pharmacology, therapeutic use)
• Androgen Receptor Antagonists
• Animals
• Indicators and Reagents
• Magnetic Resonance Spectroscopy
• Male
• Mass Spectrometry
• Orchiectomy
• Piperazines (chemical synthesis, pharmacology, therapeutic use)
• Prostate (drug effects, growth & development)
• Prostatic Neoplasms (drug therapy)
• Rats
• Rats, Wistar
• Testosterone (pharmacology)