4-azonan-1-ylbenzoic acid | 918129-38-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-azonan-1-ylbenzoic acid
• 英文别名: 4-(Azonan-1-yl)benzoic acid；4-(azonan-1-yl)benzoic acid
• CAS: 918129-38-1
• 化学式: C₁₅H₂₁NO₂
• 分子量: 247.337
• InChiKey: NAIWUWVVURQVRL-UHFFFAOYSA-N

物化性质

• 沸点：
  427.5±28.0 °C(Predicted)
• 密度：
  1.087±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-azonan-1-ylbenzoic acid 在 lithium hydroxide monohydrate 、 双氧水 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.5h， 生成 (2R)-2-[[3-[[[4-(azonan-1-yl)benzoyl]amino]methyl]-4-propoxyphenyl]methyl]-3-phenylpropanoic acid
  参考文献：
  名称：

  Molecular dynamics study-guided identification of cyclic amine structures as novel hydrophobic tail components of hPPARγ agonists

  摘要：

  We previously reported that a α-benzylphenylpropanoic acid-type hPPARγ-selective agonist with a piperidine ring as the hydrophobic tail part (3) exhibited sub-micromolar-order hPPARγ agonistic activity. In order to enhance the activity, we planned to carry out structural development based on information obtained from the X-ray crystal structure of hPPARγ ligand binding domain (LBD) complexed with 3. However, the shape and/or nature of the binding pocket surrounding the piperidine ring of 3 could not be precisely delineated because the structure of the omega loop of the LBD was poorly defined. Therefore, we constructed and inserted a plausible omega loop by means of molecular dynamics simulation. We then used the reconstructed LBD structure to design new mono-, bi- and tricyclic amine-bearing compounds that might be expected to show greater binding affinity for the LBD. Here, we describe synthesis and evaluation of α-benzylphenylpropanoic acid derivatives 8. As expected, most of the newly synthesized compounds exhibited more potent hPPARγ agonistic activity and greater hPPARγ binding affinity than 3. Some of these compounds also showed comparable aqueous solubility to 3.

  DOI：

  10.1016/j.bmcl.2014.06.023
• 作为产物：
  描述：

  2,2,2,4'-四氟苯乙酮 在 sodium hydroxide 、 三乙胺 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 4-azonan-1-ylbenzoic acid
  参考文献：
  名称：

  一种制备 4-氮取代苯甲酸的实用方法

  摘要：

  描述了一种有效且实用的制备 4-氮取代苯甲酸的方法。我们的方法包括 2,2,2,4'-四氟苯乙酮与胺的芳香取代，然后是苯甲酸的卤仿反应。在该方法中，即使对于亲核性较低的 7-、8-和 9-元胺 1 当量。使用时，相应的苯甲酸以中等至极好的收率获得。由于包括纯化在内的实验步骤简单，该方法适用于大规模合成。

  DOI：

  10.1246/cl.2006.1090

文献信息

• A Practical Method for the Preparation of 4-Nitrogen-substituted Benzoic Acids
  作者：Tsuyoshi Shinozuka、Akira Nakao、Keiji Saito、Satoru Naito

  DOI：10.1246/cl.2006.1090

  日期：2006.10

  efficient and practical method for the preparation of 4-nitrogen-substituted benzoic acids is described. Our method consists of the aromatic substitution of 2,2,2,4'-tetrafluoroacetophenone with amines, followed by haloform reaction to the benzoic acids. In this method, even though for the less nucleophilic 7-, 8-, and 9-membered amines 1 equiv. was used, corresponding benzoic acids were obtained in moderate

  描述了一种有效且实用的制备 4-氮取代苯甲酸的方法。我们的方法包括 2,2,2,4'-四氟苯乙酮与胺的芳香取代，然后是苯甲酸的卤仿反应。在该方法中，即使对于亲核性较低的 7-、8-和 9-元胺 1 当量。使用时，相应的苯甲酸以中等至极好的收率获得。由于包括纯化在内的实验步骤简单，该方法适用于大规模合成。
• Molecular dynamics study-guided identification of cyclic amine structures as novel hydrophobic tail components of hPPARγ agonists
  作者：Yuta Tanaka、Kanae Gamo、Takuji Oyama、Masao Ohashi、Minoru Waki、Kenji Matsuno、Nobuyasu Matsuura、Hiroaki Tokiwa、Hiroyuki Miyachi

  DOI：10.1016/j.bmcl.2014.06.023

  日期：2014.8

  We previously reported that a α-benzylphenylpropanoic acid-type hPPARγ-selective agonist with a piperidine ring as the hydrophobic tail part (3) exhibited sub-micromolar-order hPPARγ agonistic activity. In order to enhance the activity, we planned to carry out structural development based on information obtained from the X-ray crystal structure of hPPARγ ligand binding domain (LBD) complexed with 3. However, the shape and/or nature of the binding pocket surrounding the piperidine ring of 3 could not be precisely delineated because the structure of the omega loop of the LBD was poorly defined. Therefore, we constructed and inserted a plausible omega loop by means of molecular dynamics simulation. We then used the reconstructed LBD structure to design new mono-, bi- and tricyclic amine-bearing compounds that might be expected to show greater binding affinity for the LBD. Here, we describe synthesis and evaluation of α-benzylphenylpropanoic acid derivatives 8. As expected, most of the newly synthesized compounds exhibited more potent hPPARγ agonistic activity and greater hPPARγ binding affinity than 3. Some of these compounds also showed comparable aqueous solubility to 3.