1'-benzyl-3-(fluoromethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine] | 1355357-51-5

• 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-3-(fluoromethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]
• 英文别名: WMS-1850；1'-benzyl-1-(fluoromethyl)spiro[1H-2-benzofuran-3,4'-piperidine]
• CAS: 1355357-51-5
• 化学式: C₂₀H₂₂FNO
• 分子量: 311.399
• InChiKey: XTXVTJGNOBELJF-UHFFFAOYSA-N

物化性质

• 沸点：
  442.0±45.0 °C(Predicted)
• 密度：
  1.18±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1'-benzyl-3-(fluoromethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine] 在 potassium [¹⁸F]fluoride 、 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 0.42h， 生成 [18F]1'-benzyl-3-(fluoromethyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]
  参考文献：
  名称：

  设计用于正电子发射断层成像的（无线电）氟化σ1受体配体同源系列的硅胶，电化学，体外和体内代谢的比较

  摘要：

  σ的成像1种受体在脑中由氟化的放射性示踪剂将用于σ的验证1个受体的药物靶标，以及用于在中枢神经系统疾病的鉴别诊断。4个同源的生物转化氟化PET示踪剂1'-苄基-3-（ω-氟到ω氟丁基）-3 ħ -螺[2]苯并呋喃-1,4'-哌啶]（[ 18 F] 1 - 4）被调查了。在使用快速代谢（FAME）软件，电化学氧化，在体外研究用大鼠肝微粒体硅的研究，在体内代谢研究的PET示踪剂的应用后[ 18 F] 1 - 4对小鼠进行。液相色谱和质谱联用（HPLC–MS）分析可以对非放射性代谢物进行结构鉴定。放射性HPLC和radio-TLC提供了有关未改变的母体放射性示踪剂及其放射性代谢物的信息。Radiometabolites均未的[应用后脑中发现18 F] 2 - 4，但肝脏，血浆和尿样品含有几个radiometabolites。少于2％的[ 18 F] 4注射剂量到达大脑，使得[ 18 F] 4较[

  DOI：

  10.1002/cmdc.201600366
• 作为产物：
  描述：

  1''-Benzylspiro[1,3-dihydroisobenzofuran-1,4''-(hexahydropyridine)]-3-ylmethanol 在 二乙胺基三氟化硫 作用下， 以 二氯甲烷 为溶剂， 以70%的产率得到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

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.
• Comparison of in Silico, Electrochemical, in Vitro and in Vivo Metabolism of a Homologous Series of (Radio)fluorinated σ₁Receptor Ligands Designed for Positron Emission Tomography
  作者：Christian Wiese、Eva Große Maestrup、Fabian Galla、Dirk Schepmann、Achim Hiller、Steffen Fischer、Friedrich-Alexander Ludwig、Winnie Deuther-Conrad、Cornelius K. Donat、Peter Brust、Lars Büter、Uwe Karst、Bernhard Wünsch

  DOI：10.1002/cmdc.201600366

  日期：2016.11.7

  metabolizer (FAME) software, electrochemical oxidations, in vitro studies with rat liver microsomes, and in vivo metabolism studies after application of the PET tracers [18F]1–4 to mice were performed. Combined liquid chromatography and mass spectrometry (HPLC–MS) analysis allowed structural identification of non‐radioactive metabolites. Radio‐HPLC and radio‐TLC provided information about the presence

  σ的成像1种受体在脑中由氟化的放射性示踪剂将用于σ的验证1个受体的药物靶标，以及用于在中枢神经系统疾病的鉴别诊断。4个同源的生物转化氟化PET示踪剂1'-苄基-3-（ω-氟到ω氟丁基）-3 ħ -螺[2]苯并呋喃-1,4'-哌啶]（[ 18 F] 1 - 4）被调查了。在使用快速代谢（FAME）软件，电化学氧化，在体外研究用大鼠肝微粒体硅的研究，在体内代谢研究的PET示踪剂的应用后[ 18 F] 1 - 4对小鼠进行。液相色谱和质谱联用（HPLC–MS）分析可以对非放射性代谢物进行结构鉴定。放射性HPLC和radio-TLC提供了有关未改变的母体放射性示踪剂及其放射性代谢物的信息。Radiometabolites均未的[应用后脑中发现18 F] 2 - 4，但肝脏，血浆和尿样品含有几个radiometabolites。少于2％的[ 18 F] 4注射剂量到达大脑，使得[ 18 F] 4较[