1-(3-isopropoxybenzyl)-2-methylpiperidin-4-one | 921599-67-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(3-isopropoxybenzyl)-2-methylpiperidin-4-one
• 英文别名: 2-methyl-1-[(3-propan-2-yloxyphenyl)methyl]piperidin-4-one
• CAS: 921599-67-9
• 化学式: C₁₆H₂₃NO₂
• 分子量: 261.364
• InChiKey: IYEPPIPZMXTNTA-UHFFFAOYSA-N

物化性质

• 沸点：
  378.3±27.0 °C(Predicted)
• 密度：
  1.046±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-isopropoxybenzyl)-2-methylpiperidin-4-one 在 氯化亚砜 、 二乙胺 作用下， 以 甲醇 、 正己烷 、 氯仿 、 醋酸异丙酯 为溶剂， 反应 19.0h， 生成 (5R,7S)-4-(cyclohexylamino)-1-(3-fluorophenyl)-8-(3-isopropoxybenzyl)-7-methyl-1,3,8-triazaspiro[4.5]dec-3-en-2-one
  参考文献：
  名称：

  Methyl-substitution of an iminohydantoin spiropiperidine β-secretase (BACE-1) inhibitor has a profound effect on its potency

  摘要：

  The IC50 of a beta-secretase (BACE-1) lead compound was improved similar to 200-fold from 11 mu M to 55 nM through the addition of a single methyl group. Computational chemistry, small molecule NMR, and protein crystallography capabilities were used to compare the solution conformation of the ligand under varying pH conditions to its conformation when bound in the active site. Chemical modification then explored available binding pockets adjacent to the ligand. A strategically placed methyl group not only maintained the required pKa of the piperidine nitrogen and filled a small hydrophobic pocket, but more importantly, stabilized the conformation best suited for optimized binding to the receptor. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.06.082
• 作为产物：
  描述：

  3-氰基苯酚 在 氢气 、 碳酸氢钠 、 caesium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 20.0 ℃ 、275.8 kPa 条件下， 反应 19.0h， 生成 1-(3-isopropoxybenzyl)-2-methylpiperidin-4-one
  参考文献：
  名称：

  Methyl-substitution of an iminohydantoin spiropiperidine β-secretase (BACE-1) inhibitor has a profound effect on its potency

  摘要：

  The IC50 of a beta-secretase (BACE-1) lead compound was improved similar to 200-fold from 11 mu M to 55 nM through the addition of a single methyl group. Computational chemistry, small molecule NMR, and protein crystallography capabilities were used to compare the solution conformation of the ligand under varying pH conditions to its conformation when bound in the active site. Chemical modification then explored available binding pockets adjacent to the ligand. A strategically placed methyl group not only maintained the required pKa of the piperidine nitrogen and filled a small hydrophobic pocket, but more importantly, stabilized the conformation best suited for optimized binding to the receptor. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.06.082

文献信息

• Spiropiperidine beta-secretase inhibitors for the treatment of Alzheimer's disease
  申请人：Coburn A. Craig

  公开号：US20070021454A1

  公开（公告）日：2007-01-25

  The present invention is directed to spiropiperidine compounds of formula (I) and tautomers thereof, 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）及其互变异构体的螺环吡啶化合物，这些化合物是β-分泌酶酶的抑制剂，并且在治疗β-分泌酶酶参与的疾病，如阿尔茨海默病方面是有用的。本发明还涉及包括这些化合物的制药组合物以及在治疗β-分泌酶酶参与的这些疾病中使用这些化合物和组合物的用途。
• Spiropiperidine beta-secretase inhibitors for the treatment of alzheimer's disease
  申请人：Merck, Sharp & Dohme Corp.

  公开号：US08211904B2

  公开（公告）日：2012-07-03

  The present invention is directed to spiropiperidine compounds of formula (I) and tautomers thereof, 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)的螺环吡啶化合物及其互变异构体，其为β-分泌酶酶抑制剂，可用于治疗涉及β-分泌酶酶的疾病，如阿尔茨海默病。本发明还涉及包含这些化合物的制药组合物以及将这些化合物和组合物用于治疗涉及β-分泌酶酶的疾病的用途。
• Spiropiperidine beta-secretase inhibitors for the treatment of Alzheimer's Disease
  申请人：Egbertson Melissa S.

  公开号：US20100298342A1

  公开（公告）日：2010-11-25

  The present invention is directed to spiropiperidine compounds of formula (I) and tautomers thereof, 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)的螺环吡啶化合物及其互变异构体，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药物组合物以及这些化合物和组合物在治疗β-分泌酶酶参与的这些疾病中的使用。
• WO2007/11810
  申请人：——

  公开号：——

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

  公开号：EP1910364A2

  公开（公告）日：2008-04-16