N-Arylpiperazine-1-carboxamide derivatives: a novel series of orally active nonsteroidal androgen receptor antagonists |
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Authors: | Kinoyama Isao Taniguchi Nobuaki Kawaminami Eiji Nozawa Eisuke Koutoku Hiroshi Furutani Takashi Kudoh Masafumi Okada Minoru |
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Institution: | Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki. kinoyama@yamanouchi.co.jp |
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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. |
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