3'-benzyloxy-spiro{8-azabicyclo[3.2.1]octane-3,5'(4'H)isoxazole}

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: 3'-benzyloxy-spiro{8-azabicyclo[3.2.1]octane-3,5'(4'H)isoxazole}
• 英文别名: (1'S,5'R)-3-phenylmethoxyspiro[4H-1,2-oxazole-5,3'-8-azabicyclo[3.2.1]octane]
• 化学式: C₁₆H₂₀N₂O₂
• 分子量: 272.347
• InChiKey: PPJDSTGGORILAA-MZBDJJRSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  42.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3'-benzyloxy-spiro{8-azabicyclo[3.2.1]octane-3,5'(4'H)isoxazole} 在 10% Pd/C 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 6.0h， 生成 3'-oxo-8-methyl-spiro{8-azabicyclo[3.2.1]octane-3,5'-isoxazolidine}
  参考文献：
  名称：

  A novel spirocyclic tropanyl-Δ2-isoxazoline derivative enhances citalopram and paroxetine binding to serotonin transporters as well as serotonin uptake

  摘要：

  A group of spirocyclic tropanyl-Delta(2)-isoxazolines was synthesized exploiting the 1,3-dipolar cycloaddition of nitrite oxides to olefins. Their interaction with the dopamine and serotonin transporters (DAT and SERT, respectively) was evaluated through binding experiments. The majority of the compounds had no inhibitory effects (IC50 >> 10 mu M), while some had an IC50 value in the range 5-10 mu M (8a-c, 10b and 11c on DAT, 12b on SERT). Unexpectedly, one of the tertiary amines under investigation, that is 3'-methoxy-8-methyl-spiro{8-azabicyclo[3.2.1]octane-3,5'(4'H)-isoxazole 7a, was able to enhance at a concentration of 10 mu M both [H-3]citalopram and [H-3]paroxetine binding to SERT in rat brain homogenate (up to 25%, due to an increase of B-max) and [H-3]serotonin uptake (up to 30%) in cortical synaptosomes. This peculiar pharmacological profile of 7a suggests it binds to an allosteric site on SERT, and positions derivative 7a as a very useful tool to investigate SERT machinery. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.004
• 作为产物：
  描述：

  tert-butyl 3'-benzyloxy-spiro{8-azabicyclo[3.2.1]octane-3,5'(4'H)-isoxazole}-8-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以58%的产率得到3'-benzyloxy-spiro{8-azabicyclo[3.2.1]octane-3,5'(4'H)isoxazole}
  参考文献：
  名称：

  A novel spirocyclic tropanyl-Δ2-isoxazoline derivative enhances citalopram and paroxetine binding to serotonin transporters as well as serotonin uptake

  摘要：

  A group of spirocyclic tropanyl-Delta(2)-isoxazolines was synthesized exploiting the 1,3-dipolar cycloaddition of nitrite oxides to olefins. Their interaction with the dopamine and serotonin transporters (DAT and SERT, respectively) was evaluated through binding experiments. The majority of the compounds had no inhibitory effects (IC50 >> 10 mu M), while some had an IC50 value in the range 5-10 mu M (8a-c, 10b and 11c on DAT, 12b on SERT). Unexpectedly, one of the tertiary amines under investigation, that is 3'-methoxy-8-methyl-spiro{8-azabicyclo[3.2.1]octane-3,5'(4'H)-isoxazole 7a, was able to enhance at a concentration of 10 mu M both [H-3]citalopram and [H-3]paroxetine binding to SERT in rat brain homogenate (up to 25%, due to an increase of B-max) and [H-3]serotonin uptake (up to 30%) in cortical synaptosomes. This peculiar pharmacological profile of 7a suggests it binds to an allosteric site on SERT, and positions derivative 7a as a very useful tool to investigate SERT machinery. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.004

文献信息

• A novel spirocyclic tropanyl-Δ2-isoxazoline derivative enhances citalopram and paroxetine binding to serotonin transporters as well as serotonin uptake
  作者：Clelia Dallanoce、Mara Canovi、Carlo Matera、Tiziana Mennini、Marco De Amici、Marco Gobbi、Carlo De Micheli

  DOI：10.1016/j.bmc.2012.09.004

  日期：2012.11

  A group of spirocyclic tropanyl-Delta(2)-isoxazolines was synthesized exploiting the 1,3-dipolar cycloaddition of nitrite oxides to olefins. Their interaction with the dopamine and serotonin transporters (DAT and SERT, respectively) was evaluated through binding experiments. The majority of the compounds had no inhibitory effects (IC50 >> 10 mu M), while some had an IC50 value in the range 5-10 mu M (8a-c, 10b and 11c on DAT, 12b on SERT). Unexpectedly, one of the tertiary amines under investigation, that is 3'-methoxy-8-methyl-spiro8-azabicyclo[3.2.1]octane-3,5'(4'H)-isoxazole 7a, was able to enhance at a concentration of 10 mu M both [H-3]citalopram and [H-3]paroxetine binding to SERT in rat brain homogenate (up to 25%, due to an increase of B-max) and [H-3]serotonin uptake (up to 30%) in cortical synaptosomes. This peculiar pharmacological profile of 7a suggests it binds to an allosteric site on SERT, and positions derivative 7a as a very useful tool to investigate SERT machinery. (C) 2012 Elsevier Ltd. All rights reserved.