4-[4-(4-acetyl-3-hydroxy-2-propylphenoxy)butoxy]benzonitrile | 847987-60-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[4-(4-acetyl-3-hydroxy-2-propylphenoxy)butoxy]benzonitrile
• CAS: 847987-60-4
• 化学式: C₂₂H₂₅NO₄
• 分子量: 367.445
• InChiKey: DDUDDLIPSQQZHE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  79.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[4-(4-acetyl-3-hydroxy-2-propylphenoxy)butoxy]benzonitrile 在 叠氮基三甲基硅烷 、 二正丁基氧化锡 作用下， 以 甲苯 为溶剂， 反应 16.0h， 以6.09 g的产率得到1-[2-hydroxy-3-propyl-4-[4-[4-(2H-tetrazol-5-yl)phenoxy]butoxy]phenyl]ethanone
  参考文献：
  名称：

  Phenyl-tetrazolyl Acetophenones:  Discovery of Positive Allosteric Potentiatiors for the Metabotropic Glutamate 2 Receptor

  摘要：

  Herein we disclose the discovery of a new class of positive allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2), phenyl-tetrazolyl acetophenones, e.g. 1-(2-hydroxy-3-propyl-4-{4-[4-(2H-tetrazol-5-yl)phenoxy]butoxy}phenyl) ethanone (4). These potentiators were shown to have no effect in the absence of glutamate as well as no effect at mGlu3 or the other mGlu receptors. The compounds were also evaluated in rodent models with potential relevance for schizophrenia, and 4 was shown to have activity in the inhibition of ketamine-induced norepinephrine release and ketamine-induced hyperactivity. This represents the first example of the efficacy of mGlu2 receptor potentiators in these models.

  DOI：

  10.1021/jm040088h
• 作为产物：
  描述：

  2-正丙基间苯二酚 在 三氯化铝 、 potassium carbonate 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 生成 4-[4-(4-acetyl-3-hydroxy-2-propylphenoxy)butoxy]benzonitrile
  参考文献：
  名称：

  Allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2). Part 1: Identification and synthesis of phenyl-tetrazolyl acetophenones

  摘要：

  We have identified and synthesized a series of aryl-tetrazoyl acetophenones as positive allosteric potentiators of the metabotropic glutamate receptor 2. Structure activity relationship studies directed toward improving the potency and level of potentiation led to the discovery of 22 (EC50 = 93 nM, 128% potentiation). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.020

文献信息

• Allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2). Part 1: Identification and synthesis of phenyl-tetrazolyl acetophenones
  作者：Anthony B. Pinkerton、Rowena V. Cube、John H. Hutchinson、Blake A. Rowe、Hervé Schaffhauser、Xiumin Zhao、Lorrie P. Daggett、Jean-Michel Vernier

  DOI：10.1016/j.bmcl.2004.08.020

  日期：2004.11

  We have identified and synthesized a series of aryl-tetrazoyl acetophenones as positive allosteric potentiators of the metabotropic glutamate receptor 2. Structure activity relationship studies directed toward improving the potency and level of potentiation led to the discovery of 22 (EC50 = 93 nM, 128% potentiation). (C) 2004 Elsevier Ltd. All rights reserved.
• Phenyl-tetrazolyl Acetophenones:  Discovery of Positive Allosteric Potentiatiors for the Metabotropic Glutamate 2 Receptor
  作者：Anthony B. Pinkerton、Jean-Michel Vernier、Hervé Schaffhauser、Blake A. Rowe、Una C. Campbell、Dana E. Rodriguez、Daniel S. Lorrain、Christopher S. Baccei、Lorrie P. Daggett、Linda J. Bristow

  DOI：10.1021/jm040088h

  日期：2004.8.1

  Herein we disclose the discovery of a new class of positive allosteric potentiators of the metabotropic glutamate receptor 2 (mGlu2), phenyl-tetrazolyl acetophenones, e.g. 1-(2-hydroxy-3-propyl-4-4-[4-(2H-tetrazol-5-yl)phenoxy]butoxy}phenyl) ethanone (4). These potentiators were shown to have no effect in the absence of glutamate as well as no effect at mGlu3 or the other mGlu receptors. The compounds were also evaluated in rodent models with potential relevance for schizophrenia, and 4 was shown to have activity in the inhibition of ketamine-induced norepinephrine release and ketamine-induced hyperactivity. This represents the first example of the efficacy of mGlu2 receptor potentiators in these models.