(+/-)-trans-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-piperazine-1-[N-(6-cyanopyridin-3-yl)]carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (+/-)-trans-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-piperazine-1-[N-(6-cyanopyridin-3-yl)]carboxamide
• 英文别名: (2S,5R)-N-(6-cyanopyridin-3-yl)-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethylpiperazine-1-carboxamide
• 化学式: C₂₁H₁₉F₃N₆O
• 分子量: 428.417
• InChiKey: LXGRLACDWXGBOS-KGLIPLIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  31
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  96
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-氟-2-(三氟甲基)苯甲腈 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 21.17h， 生成 (+/-)-trans-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-piperazine-1-[N-(6-cyanopyridin-3-yl)]carboxamide
  参考文献：
  名称：

  (+)-(2R,5S)-4-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-N-[6-(trifluoromethyl)pyridin-3- yl]piperazine-1-carboxamide (YM580) as an Orally Potent and Peripherally Selective Nonsteroidal Androgen Receptor Antagonist

  摘要：

  A novel series of trans-N-aryl-2,5-dimethylpiperazine-1-carboxamide derivatives was synthesized and their androgen receptor (AR) antagonist activities and in vivo antiandrogenic effects were evaluated. Pharmacological assays indicated that compound 33 was a potent AR antagonist, and subsequent optical resolution provided (+)-(2R,5S)-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-N-[6-(trifluoromethyl)pyridin-3-yl]piperazine-1-carboxamide (33a, YM580) which exhibited the most potent antiandrogenic activity. Unlike bicalutamide, compound 33a decreased the weight of rat ventral prostate in a dose-dependent manner (ED50 = 2.2 mg/kg/day), and induced the maximum antiandrogenic effect, comparable to that of surgical castration, without significantly affecting serum testosterone levels. Compound 33a is a promising clinical candidate for prostate cancer monotherapy.

  DOI：

  10.1021/jm050293c

文献信息

• (+)-(<i>2R</i>,<i>5S</i>)-4-[4-Cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-<i>N</i>-[6-(trifluoromethyl)pyridin-3- yl]piperazine-1-carboxamide (YM580) as an Orally Potent and Peripherally Selective Nonsteroidal Androgen Receptor Antagonist
  作者：Isao Kinoyama、Nobuaki Taniguchi、Akira Toyoshima、Eisuke Nozawa、Takashi Kamikubo、Masakazu Imamura、Akira Matsuhisa、Kiyohiro Samizu、Eiji Kawanimani、Tatsuya Niimi、Noritaka Hamada、Hiroshi Koutoku、Takashi Furutani、Masafumi Kudoh、Minoru Okada、Mitsuaki Ohta、Shin-ichi Tsukamoto

  DOI：10.1021/jm050293c

  日期：2006.1.1

  A novel series of trans-N-aryl-2,5-dimethylpiperazine-1-carboxamide derivatives was synthesized and their androgen receptor (AR) antagonist activities and in vivo antiandrogenic effects were evaluated. Pharmacological assays indicated that compound 33 was a potent AR antagonist, and subsequent optical resolution provided (+)-(2R,5S)-4-[4-cyano-3-(trifluoromethyl)phenyl]-2,5-dimethyl-N-[6-(trifluoromethyl)pyridin-3-yl]piperazine-1-carboxamide (33a, YM580) which exhibited the most potent antiandrogenic activity. Unlike bicalutamide, compound 33a decreased the weight of rat ventral prostate in a dose-dependent manner (ED50 = 2.2 mg/kg/day), and induced the maximum antiandrogenic effect, comparable to that of surgical castration, without significantly affecting serum testosterone levels. Compound 33a is a promising clinical candidate for prostate cancer monotherapy.