[(1'-benzyl-3H-spiro[[2]benzofuran-1,4'-piperidin]-3-yl)]-methyl tosylate | 1355357-58-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: [(1'-benzyl-3H-spiro[[2]benzofuran-1,4'-piperidin]-3-yl)]-methyl tosylate
• 英文别名: (1'-benzylspiro[1H-2-benzofuran-3,4'-piperidine]-1-yl)methyl 4-methylbenzenesulfonate
• CAS: 1355357-58-2
• 化学式: C₂₇H₂₉NO₄S
• 分子量: 463.598
• InChiKey: LNSDBQZKTBJDIA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [(1'-benzyl-3H-spiro[[2]benzofuran-1,4'-piperidin]-3-yl)]-methyl tosylate 在 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 作用下， 以 二甲基亚砜 为溶剂， 反应 0.33h， 生成 [18F]1'-benzyl-3-(fluoromethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]
  参考文献：
  名称：

  Synthesis, radiofluorination and pharmacological evaluation of a fluoromethyl spirocyclic PET tracer for central σ1 receptors and comparison with fluoroalkyl homologs

  摘要：

  The spirocyclicr1 receptor ligand 1 (1'-benzyl-3-(fluoromethyl)-3H-spiro[[2] benzofuran-1,4'-piperidine]) was prepared in four steps starting from methoxy derivative 5. Due to its high sigma(1) affinity (K-i = 0.74 nM) and selectivity against several other relevant targets, 1 was investigated as F-18-labeled PET tracer and its biological properties were compared with those of homologous fluoroalkyl derivatives 2-4. The fluoromethyl derivative 1 was faster metabolized in vitro than homologs 2-4. In contrast to the radiosynthesis of [F-18]2-4, the nucleophilic substitution of the tosylate 15 using the K[F-18]F-K-222-carbonate complex required heating to 150 degrees C in DMSO to achieve high labeling efficiencies. Whereas radiometabolites of [F-18]2-4 were not detected in vivo in the brain of mice, two radiometabolites of [F-18]1 were found. Analysis of ex vivo autoradiography images provided rather low target-to-nontarget ratio for [F-18]1 compared with [F-18]2-4. [F-18]1 showed a fast uptake in the brain, which decreased continuously over time. The brain-to-plasma ratio of the radiotracer [F-18]1 was only exceeded by the fluoroethyl tracer [F-18]2. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.002
• 作为产物：
  描述：

  1'-tert-butyl 3-ethyl 1'H,3H-spiro[2-benzofuran-1,4'-piperidine]-1',3-dicarboxylate 在 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 [(1'-benzyl-3H-spiro[[2]benzofuran-1,4'-piperidin]-3-yl)]-methyl tosylate
  参考文献：
  名称：

  Synthesis, radiofluorination and pharmacological evaluation of a fluoromethyl spirocyclic PET tracer for central σ1 receptors and comparison with fluoroalkyl homologs

  摘要：

  The spirocyclicr1 receptor ligand 1 (1'-benzyl-3-(fluoromethyl)-3H-spiro[[2] benzofuran-1,4'-piperidine]) was prepared in four steps starting from methoxy derivative 5. Due to its high sigma(1) affinity (K-i = 0.74 nM) and selectivity against several other relevant targets, 1 was investigated as F-18-labeled PET tracer and its biological properties were compared with those of homologous fluoroalkyl derivatives 2-4. The fluoromethyl derivative 1 was faster metabolized in vitro than homologs 2-4. In contrast to the radiosynthesis of [F-18]2-4, the nucleophilic substitution of the tosylate 15 using the K[F-18]F-K-222-carbonate complex required heating to 150 degrees C in DMSO to achieve high labeling efficiencies. Whereas radiometabolites of [F-18]2-4 were not detected in vivo in the brain of mice, two radiometabolites of [F-18]1 were found. Analysis of ex vivo autoradiography images provided rather low target-to-nontarget ratio for [F-18]1 compared with [F-18]2-4. [F-18]1 showed a fast uptake in the brain, which decreased continuously over time. The brain-to-plasma ratio of the radiotracer [F-18]1 was only exceeded by the fluoroethyl tracer [F-18]2. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.002

文献信息

• Synthesis, radiofluorination and pharmacological evaluation of a fluoromethyl spirocyclic PET tracer for central σ1 receptors and comparison with fluoroalkyl homologs
  作者：Aurélie Maisonial、Eva Große Maestrup、Christian Wiese、Achim Hiller、Dirk Schepmann、Steffen Fischer、Winnie Deuther-Conrad、Jörg Steinbach、Peter Brust、Bernhard Wünsch

  DOI：10.1016/j.bmc.2011.11.002

  日期：2012.1

  The spirocyclicr1 receptor ligand 1 (1'-benzyl-3-(fluoromethyl)-3H-spiro[[2] benzofuran-1,4'-piperidine]) was prepared in four steps starting from methoxy derivative 5. Due to its high sigma(1) affinity (K-i = 0.74 nM) and selectivity against several other relevant targets, 1 was investigated as F-18-labeled PET tracer and its biological properties were compared with those of homologous fluoroalkyl derivatives 2-4. The fluoromethyl derivative 1 was faster metabolized in vitro than homologs 2-4. In contrast to the radiosynthesis of [F-18]2-4, the nucleophilic substitution of the tosylate 15 using the K[F-18]F-K-222-carbonate complex required heating to 150 degrees C in DMSO to achieve high labeling efficiencies. Whereas radiometabolites of [F-18]2-4 were not detected in vivo in the brain of mice, two radiometabolites of [F-18]1 were found. Analysis of ex vivo autoradiography images provided rather low target-to-nontarget ratio for [F-18]1 compared with [F-18]2-4. [F-18]1 showed a fast uptake in the brain, which decreased continuously over time. The brain-to-plasma ratio of the radiotracer [F-18]1 was only exceeded by the fluoroethyl tracer [F-18]2. (C) 2011 Elsevier Ltd. All rights reserved.