4-benzyl-2-((naphth-1-yloxy)methyl)morpholine | 56220-64-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-benzyl-2-((naphth-1-yloxy)methyl)morpholine
• 英文别名: 4-benzyl-2-naphthalen-1-yloxymethyl-morpholine；4-benzyl-2-(naphth-1-yloxymethyl)-morpholine；4-Benzyl-2-(naphthalen-1-yloxymethyl)morpholine
• CAS: 56220-64-5
• 化学式: C₂₂H₂₃NO₂
• 分子量: 333.43
• InChiKey: GXHGLWRBBFTPFW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-benzyl-2-((naphth-1-yloxy)methyl)morpholine 以60%的产率得到
  参考文献：
  名称：

  GREEMWOOD D. T.; MALLION K. B.; TODD A. H.; TURNER R. W., J. MED. CHEM. , 1975, 18, NO 6, 573-577

  摘要：

  DOI：
• 作为产物：
  描述：

  4-benzyl-6-naphthalen-1-yloxymethyl-morpholin-3-one 、 氢化铝锂 以30%的产率得到
  参考文献：
  名称：

  GREEMWOOD D. T.; MALLION K. B.; TODD A. H.; TURNER R. W., J. MED. CHEM. , 1975, 18, NO 6, 573-577

  摘要：

  DOI：

文献信息

• Morpholine derivatives
  申请人：Imperial Chemical Industries Limited

  公开号：US03959273A1

  公开（公告）日：1976-05-25

  The disclosure relates to new 2-aryloxymethylmorpholine derivatives which possess antidepressant properties, and to processes for the manufacture of the said morpholine derivatives, to pharmaceutical compositions containing them, and to a method of preventing or relieving depression in warm-blooded animals including man. Typical of the morpholine derivatives disclosed is 2-(o-ethoxyphenoxymethyl)morpholine.

  本发明涉及新的2-芳氧甲基吗啡啶衍生物，具有抗抑郁作用，并涉及制造所述吗啡啶衍生物的过程，包含它们的制药组合物以及一种预防或缓解包括人在内的温血动物抑郁症的方法。所披露的吗啡啶衍生物的典型代表是2-(o-乙氧基苯氧甲基)吗啡啶。
• Development of the First Generation of Disulfide-Based Subtype-Selective and Potent Covalent Pyruvate Dehydrogenase Kinase 1 (PDK1) Inhibitors
  作者：Yifu Liu、Zuoquan Xie、Dan Zhao、Jin Zhu、Fei Mao、Shuai Tang、Hui Xu、Cheng Luo、Meiyu Geng、Min Huang、Jian Li

  DOI：10.1021/acs.jmedchem.6b01245

  日期：2017.3.23

  Pyruvate dehydrogenase kinases (PDKs) are overexpressed in most cancer cells and are responsible for aberrant glucose metabolism. We previously described bis(4-morpholinyl thiocarbonyl)-disulfide (JX06, 16) as the first covalent inhibitor of PDK1. Here, on the basis of the scaffold of 16, we identify two novel types of disulfide-based PDK1 inhibitors. The most potent analogue, 3a, effectively inhibits PDK1 both at the molecular (k(mact)/K-i = 4.17 x 10(3) M-1 s(-1)) and the cellular level (down to 0.1 mu M). In contrast to 16, 3a is a potent and subtype-selective inhibitor of PDK1 with >40-fold selectivity for PDK2-4. 3a also significantly alters glucose metabolic pathways in A549 cells by decreasing ECAR and increasing ROS. Moreover, in the xenograft models, 3a shows significant antitumor activity with no negative effect to the mice weight. Collectively, these data demonstrate that 3a may be an excellent lead compound for the treatment of cancer as a first-generation subtype-selective and covalent PDK1 inhibitor.