4-(2-phenylethoxy)phthalonitrile | 1333116-79-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-(2-phenylethoxy)phthalonitrile
• 英文别名: 4-(2-Phenylethoxy)benzene-1,2-dicarbonitrile
• CAS: 1333116-79-2
• 化学式: C₁₆H₁₂N₂O
• 分子量: 248.284
• InChiKey: VXCBZZRQTKCOPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  56.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-phenylethoxy)phthalonitrile 在 sodium ethanolate 、 硝酸 作用下， 以 乙醇 为溶剂， 反应 2.5h， 以10%的产率得到5-(2-phenylethoxy)phthalimide
  参考文献：
  名称：

  Inhibition of monoamine oxidase by C5-substituted phthalimide analogues

  摘要：

  Literature reports that isatin as well as C5- and C6-substituted isatin analogues are reversible inhibitors of human monoamine oxidase (MAO) A and B. In general, C5- and C6-substitution of isatin leads to enhanced binding affinity to both MAO isozymes compared to isatin and in most instances result in selective binding to the MAO-B isoform. Crystallographic and modeling studies suggest that the isatin ring binds to the substrate cavities of MAO-A and -B and is stabilized by hydrogen bond interactions between the NH and the C2 carbonyl oxygen of the dioxoindolyl moiety and water molecules present in the substrate cavities of MAO-A and -B. Based on these observations and the close structural resemblances between isatin and its phthalimide isomer, a series of phthalimide analogues were synthesized and evaluated as MAO inhibitors. While phthalimide and N-aryl-substituted phthalimides were found to be weak MAO inhibitors, phthalimide homologues containing C5 substituents were potent reversible inhibitors of recombinant human MAO-B with IC(50) values ranging from 0.007 to 2.5 mu M and moderately potent reversible inhibitors of recombinant human MAO-A with IC(50) values ranging from 0.22 to 9.0 mu M. By employing molecular docking the importance of hydrogen bonding between the active sites of MAO-A and -B and the phthalimide inhibitors are highlighted. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.06.070
• 作为产物：
  描述：

  4-硝基邻苯二甲腈 、 苯乙醇 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 48.0h， 以24%的产率得到4-(2-phenylethoxy)phthalonitrile
  参考文献：
  名称：

  C4取代的邻苯二甲腈对单胺氧化酶的抑制作用

  摘要：

  最近有报道称，一系列C5取代的邻苯二甲酰亚胺是重组人单胺氧化酶（MAO）B的强效可逆抑制剂。建模研究表明，邻苯二甲酰亚胺环与MAO-B底物腔的极性区域形成许多极性相互作用，而C5侧链延伸至范德华相互作用，并通过范德华相互作用与酶进入腔的疏水区相互作用。与两个腔体的相互作用似乎是高亲和力结合的要求。在本研究中，我们已经研究了一系列C4取代的邻苯二甲腈作为潜在的人MAO抑制剂的类似物。发现邻苯二甲腈是高度有效的可逆MAO-B抑制剂，大多数类似物的IC 50均高数值在低nM范围内。邻苯二甲腈也与人MAO-A相互作用，尽管与MAO-B相比具有较低的结合亲和力。模型研究表明，邻苯二甲腈与MAO-B的高结合亲和力可能至少部分取决于腈官能团与酶底物腔之间极性相互作用的形成。对苯甲腈同系物系列的检查确定，对于相应的苯甲腈部分，邻苯二甲腈部分对MAO-B的抑制作用最佳，而与C4取代的苯甲腈相比，C3取代的苯

  DOI：

  10.1016/j.bioorg.2011.10.003

文献信息

• Monoamine oxidase inhibition by C4-substituted phthalonitriles
  作者：Clarina I. Manley-King、Jacobus J. Bergh、Jacobus P. Petzer

  DOI：10.1016/j.bioorg.2011.10.003

  日期：2012.2

  studies suggested that the phthalimide ring forms numerous polar interactions with the polar region of the MAO-B substrate cavity while the C5 side chain extends to, and interacts via Van der Waals interactions with the hydrophobic regions of the enzyme entrance cavity. Interactions with both cavities appear to be requirements for high affinity binding. In the present study we have examined an analogs series

  最近有报道称，一系列C5取代的邻苯二甲酰亚胺是重组人单胺氧化酶（MAO）B的强效可逆抑制剂。建模研究表明，邻苯二甲酰亚胺环与MAO-B底物腔的极性区域形成许多极性相互作用，而C5侧链延伸至范德华相互作用，并通过范德华相互作用与酶进入腔的疏水区相互作用。与两个腔体的相互作用似乎是高亲和力结合的要求。在本研究中，我们已经研究了一系列C4取代的邻苯二甲腈作为潜在的人MAO抑制剂的类似物。发现邻苯二甲腈是高度有效的可逆MAO-B抑制剂，大多数类似物的IC 50均高数值在低nM范围内。邻苯二甲腈也与人MAO-A相互作用，尽管与MAO-B相比具有较低的结合亲和力。模型研究表明，邻苯二甲腈与MAO-B的高结合亲和力可能至少部分取决于腈官能团与酶底物腔之间极性相互作用的形成。对苯甲腈同系物系列的检查确定，对于相应的苯甲腈部分，邻苯二甲腈部分对MAO-B的抑制作用最佳，而与C4取代的苯甲腈相比，C3取代的苯
• Inhibition of monoamine oxidase by C5-substituted phthalimide analogues
  作者：Clarina I. Manley-King、Jacobus J. Bergh、Jacobus P. Petzer

  DOI：10.1016/j.bmc.2011.06.070

  日期：2011.8

  Literature reports that isatin as well as C5- and C6-substituted isatin analogues are reversible inhibitors of human monoamine oxidase (MAO) A and B. In general, C5- and C6-substitution of isatin leads to enhanced binding affinity to both MAO isozymes compared to isatin and in most instances result in selective binding to the MAO-B isoform. Crystallographic and modeling studies suggest that the isatin ring binds to the substrate cavities of MAO-A and -B and is stabilized by hydrogen bond interactions between the NH and the C2 carbonyl oxygen of the dioxoindolyl moiety and water molecules present in the substrate cavities of MAO-A and -B. Based on these observations and the close structural resemblances between isatin and its phthalimide isomer, a series of phthalimide analogues were synthesized and evaluated as MAO inhibitors. While phthalimide and N-aryl-substituted phthalimides were found to be weak MAO inhibitors, phthalimide homologues containing C5 substituents were potent reversible inhibitors of recombinant human MAO-B with IC(50) values ranging from 0.007 to 2.5 mu M and moderately potent reversible inhibitors of recombinant human MAO-A with IC(50) values ranging from 0.22 to 9.0 mu M. By employing molecular docking the importance of hydrogen bonding between the active sites of MAO-A and -B and the phthalimide inhibitors are highlighted. (C) 2011 Elsevier Ltd. All rights reserved.