tert-butyl 4-(cyclohexylamino)-1-(3-fluorophenyl)-2-oxo-1,3,8-triazaspiro[4.5]dec-3-ene-8-carboxylate | 885115-45-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: tert-butyl 4-(cyclohexylamino)-1-(3-fluorophenyl)-2-oxo-1,3,8-triazaspiro[4.5]dec-3-ene-8-carboxylate
• 英文别名: Tert-butyl 4-(cyclohexylamino)-1-(3-fluorophenyl)-2-oxo-1,3,8-triazaspiro[4.5]dec-3-ene-8-carboxylate；tert-butyl 4-cyclohexylimino-1-(3-fluorophenyl)-2-oxo-1,3,8-triazaspiro[4.5]decane-8-carboxylate
• CAS: 885115-45-7
• 化学式: C₂₄H₃₃FN₄O₃
• 分子量: 444.549
• InChiKey: ALWXJBQAEMOEJN-UHFFFAOYSA-N

物化性质

• 沸点：
  553.9±60.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(cyclohexylamino)-1-(3-fluorophenyl)-2-oxo-1,3,8-triazaspiro[4.5]dec-3-ene-8-carboxylate 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 0.5h， 以2.74 g的产率得到4-(cyclohexylammonio)-1-(3-fluorophenyl)-2-oxo-1,3-diaza-8-azoniaspiro[4.5]dec-3-ene dichloride
  参考文献：
  名称：

  Discovery and X-ray Crystallographic Analysis of a Spiropiperidine Iminohydantoin Inhibitor of β-Secretase

  摘要：

  A high-throughput screen at 100 microM inhibitor concentration for the BACE-1 enzyme revealed a novel spiropiperidine iminohydantoin aspartyl protease inhibitor template. An X-ray cocrystal structure with BACE-1 revealed a novel mode of binding whereby the inhibitor interacts with the catalytic aspartates via bridging water molecules. Using the crystal structure as a guide, potent compounds with good brain penetration were designed.

  DOI：

  10.1021/jm800914n
• 作为产物：
  描述：

  potassium cyanate 、 异氰环已烷 、 间氟苯胺盐酸盐 、 N-叔丁氧羰基-4-哌啶酮 以 甲醇 、 水 为溶剂， 反应 2.0h， 以1.92 g的产率得到tert-butyl 4-(cyclohexylamino)-1-(3-fluorophenyl)-2-oxo-1,3,8-triazaspiro[4.5]dec-3-ene-8-carboxylate
  参考文献：
  名称：

  Discovery and X-ray Crystallographic Analysis of a Spiropiperidine Iminohydantoin Inhibitor of β-Secretase

  摘要：

  A high-throughput screen at 100 microM inhibitor concentration for the BACE-1 enzyme revealed a novel spiropiperidine iminohydantoin aspartyl protease inhibitor template. An X-ray cocrystal structure with BACE-1 revealed a novel mode of binding whereby the inhibitor interacts with the catalytic aspartates via bridging water molecules. Using the crystal structure as a guide, potent compounds with good brain penetration were designed.

  DOI：

  10.1021/jm800914n

文献信息

• Spiropiperidine compounds useful as beta-secretase inhibitors for the treatment of alzheimer' s disease
  申请人：Barrow C. James

  公开号：US20070197571A1

  公开（公告）日：2007-08-23

  The present invention is directed to spiropiperidine compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.

  本发明涉及公式（I）的螺环哌啶化合物，它们是β-分泌酶酶的抑制剂，并且在治疗β-分泌酶酶参与的疾病，如阿尔茨海默病中有用。本发明还涉及包含这些化合物的制药组合物以及这些化合物和组合物在治疗β-分泌酶酶参与的疾病中的使用。
• Spiropiperidine compounds useful as beta-secretase inhibitors for the treatment of alzheimer's disease
  申请人：Merck, Sharp & Dohme Corp.

  公开号：US08114887B2

  公开（公告）日：2012-02-14

  The present invention is directed to spiropiperidine compounds of formula (I) which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.

  本发明涉及式(I)的螺环吡啶化合物，它们是β-分泌酶酶的抑制剂，并且在治疗β-分泌酶酶涉及的疾病，如阿尔茨海默病中有用。本发明还涉及包含这些化合物的制药组合物以及这些化合物和组合物在治疗β-分泌酶酶涉及的疾病中的应用。
• WO2006/44497
  申请人：——

  公开号：——

  公开（公告）日：——
• SPIROPIPERIDINE COMPOUNDS USEFUL AS BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHERMER S DISEASE
  申请人：Merck & Co., Inc.

  公开号：EP1804794A2

  公开（公告）日：2007-07-11
• US8114887B2
  申请人：——

  公开号：US8114887B2

  公开（公告）日：2012-02-14