(+)-4-((7R)-3-(4-cyano-3-(trifluoromethyl)phenyl)-7-methyl-4-oxo-2-thioxo-1,3-diazaspiro[4.4]nonan-1-yl)-2-fluoro-N-methylbenzamide | 1608486-04-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (+)-4-((7R)-3-(4-cyano-3-(trifluoromethyl)phenyl)-7-methyl-4-oxo-2-thioxo-1,3-diazaspiro[4.4]nonan-1-yl)-2-fluoro-N-methylbenzamide
• 英文别名: 4-[(8R)-3-[4-cyano-3-(trifluoromethyl)phenyl]-8-methyl-4-oxo-2-sulfanylidene-1,3-diazaspiro[4.4]nonan-1-yl]-2-fluoro-N-methylbenzamide
• CAS: 1608486-04-9
• 化学式: C₂₄H₂₀F₄N₄O₂S
• 分子量: 504.508
• InChiKey: MDRYQSFESROUAD-JHQYKTOJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  35
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  8

文献信息

• ANDROGEN RECEPTOR VARIANTS AND METHODS FOR MAKING AND USING
  申请人：MEMORIAL SLOAN-KETTERING CANCER CENTER

  公开号：US20150265587A1

  公开（公告）日：2015-09-24

  The present invention encompasses the recognition that an F876L mutation of the androgen receptor (AR) gene confers resistance to the antiandrogens enzalutamide (MDV3100) and ARN-509 and is associated with incidence and/or risk of castration resistant prostate cancer (CRPC). The present invention also provides other AR polypeptide sequences associated with increased incidence and/or risk of CRPC. The present invention also provides screening methods for identification and/or characterization of novel AR polypeptide sequences associated with increased incidence and/or risk of CRPC via exposure to antiandrogens and for identification and/or characterization of agents to treat and/or reduce risk of CRPC by virtue of their effect on AR transcriptional activation.

  本发明涵盖了一种认识到雄激素受体（AR）基因的F876L突变赋予抗雄激素恩扎鲁胺（MDV3100）和ARN-509的耐药性，并与去势抵抗性前列腺癌（CRPC）的发生率和/或风险相关的方法。本发明还提供了与增加CRPC发生率和/或风险相关的其他AR多肽序列。本发明还提供了筛选方法，用于通过暴露于抗雄激素并确定和/或表征与增加CRPC发生率和/或风险相关的新AR多肽序列，并通过其对AR转录激活的影响确定和/或表征治疗和/或降低CRPC风险的药剂。
• Androgen receptor variants and methods for making and using
  申请人：MEMORIAL SLOAN-KETTERING CANCER CENTER

  公开号：US10206911B2

  公开（公告）日：2019-02-19

  The present invention encompasses the recognition that an F876L mutation of the androgen receptor (AR) gene confers resistance to the antiandrogens enzalutamide (MDV3100) and ARN-509 and is associated with incidence and/or risk of castration resistant prostate cancer (CRPC). The present invention also provides other AR polypeptide sequences associated with increased incidence and/or risk of CRPC. The present invention also provides screening methods for identification and/or characterization of novel AR polypeptide sequences associated with increased incidence and/or risk of CRPC via exposure to antiandrogens and for identification and/or characterization of agents to treat and/or reduce risk of CRPC by virtue of their effect on AR transcriptional activation.

  本发明包括认识到雄激素受体（AR）基因的 F876L 突变可产生对抗雄激素恩杂鲁胺（MDV3100）和 ARN-509 的耐药性，并与阉割抵抗性前列腺癌（CRPC）的发病率和/或风险有关。本发明还提供了与 CRPC 发病率和/或风险增加有关的其他 AR 多肽序列。本发明还提供了筛选方法，用于鉴定和/或表征与通过暴露于抗雄激素而增加CRPC发病率和/或风险相关的新型AR多肽序列，以及鉴定和/或表征通过影响AR转录激活而治疗和/或降低CRPC风险的药物。
• Modulators of resistant androgen receptor
  申请人：Memorial Sloan-Kettering Cancer Center

  公开号：US10450294B2

  公开（公告）日：2019-10-22

  The present invention provides compounds useful as modulators, agonists or antagonists of androgen receptor (AR), compositions thereof, and methods of making and using the same.

  本发明提供了可用作雄激素受体（AR）的调节剂、激动剂或拮抗剂的化合物、其组合物及其制造和使用方法。
• MODULATORS OF RESISTANT ANDROGEN RECEPTOR
  申请人：Memorial Sloan-Kettering Cancer Center

  公开号：EP2911666A2

  公开（公告）日：2015-09-02
• US9365542B2
  申请人：——

  公开号：US9365542B2

  公开（公告）日：2016-06-14