4-{4-[3-hydroxy-2-methyl-4-(3-methylbutyryl)phenoxy]butoxy}benzonitrile | 664376-66-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-{4-[3-hydroxy-2-methyl-4-(3-methylbutyryl)phenoxy]butoxy}benzonitrile
• 英文别名: 4-{4-[3-hydroxy-2-methyl-4-(3-methyl-butyryl)-phenoxy]-butoxy}-benzonitrile；4-[4-[3-hydroxy-2-methyl-4-(3-methylbutanoyl)phenoxy]butoxy]benzonitrile
• CAS: 664376-66-3
• 化学式: C₂₃H₂₇NO₄
• 分子量: 381.472
• InChiKey: DBKPJNPEJIYDMX-UHFFFAOYSA-N

物化性质

• 沸点：
  582.6±50.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 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-[3-hydroxy-2-methyl-4-(3-methylbutyryl)phenoxy]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， 生成 1-(2-hydroxy-3-methyl-4-{4-[4-(2H-tetrazol-5-yl)-phenoxy]-butoxy}-phenyl)-3-methyl-butan-1-one
  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
• 作为产物：
  描述：

  异戊酰氯 在 三氯化铝 、 potassium carbonate 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 生成 4-{4-[3-hydroxy-2-methyl-4-(3-methylbutyryl)phenoxy]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

• Acetophenone potentiators of metabotropic glutamate receptors
  申请人：Cube V. Rowena

  公开号：US20050288346A1

  公开（公告）日：2005-12-29

  The present invention is directed to compounds which are potentiators of metabotropic glutamate receptors, including the mGluR2 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

  本发明涉及激活型代谢型谷氨酸受体的化合物，包括mGluR2受体，适用于治疗或预防与谷氨酸功能障碍相关的神经和精神障碍以及涉及代谢型谷氨酸受体的疾病。本发明还涉及包含这些化合物的制药组合物以及使用这些化合物和组合物预防或治疗涉及代谢型谷氨酸受体的疾病。
• [EN] ACETOPHENONE POTENTIATORS OF METABOTROPIC GLUTAMATE RECEPTORS<br/>[FR] POTENTIALISATEURS ACETOPHENONES DES RECEPTEURS METABOTROPIQUES DU GLUTAMATE
  申请人：MERCK & CO INC

  公开号：WO2004018386A3

  公开（公告）日：2004-11-25
• ACETOPHENONE POTENTIATORS OF METABOTROPIC GLUTAMATE RECEPTORS
  申请人：Merck & Co., Inc.

  公开号：EP1556038A2

  公开（公告）日：2005-07-27
• 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.