3-(fluoromethyl)-1'-(1-phenylethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine] | 1355357-56-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异香豆素
• 英文名称: 3-(fluoromethyl)-1'-(1-phenylethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]
• 英文别名: 1-(fluoromethyl)-1'-(1-phenylethyl)spiro[1H-2-benzofuran-3,4'-piperidine]
• CAS: 1355357-56-0
• 化学式: C₂₁H₂₄FNO
• 分子量: 325.426
• InChiKey: HFZMUQSGLRRVPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1''-Benzylspiro[1,3-dihydroisobenzofuran-1,4''-(hexahydropyridine)]-3-ylmethanol 在 甲醇 、 二乙胺基三氟化硫 、 palladium 10% on activated carbon 、 甲酸铵 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 3-(fluoromethyl)-1'-(1-phenylethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine] 、 1'-(4-fluorobenzyl)-3-methyl-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

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.