1'-(4-fluorobenzyl)-3-methoxy-3H-spiro[[2]benzofuran-1,4'-piperidine] | 1167434-94-7

• 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'-(4-fluorobenzyl)-3-methoxy-3H-spiro[[2]benzofuran-1,4'-piperidine]
• 英文别名: 1'-[(4-fluorophenyl)methyl]-1-methoxyspiro[1H-2-benzofuran-3,4'-piperidine]
• CAS: 1167434-94-7
• 化学式: C₂₀H₂₂FNO₂
• 分子量: 327.399
• InChiKey: IZHIOJKJMMKWEY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1'-(4-fluorobenzyl)-3-methoxy-3H-spiro[[2]benzofuran-1,4'-piperidine] 在 三乙基硅烷 、 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 1.33h， 生成
  参考文献：
  名称：

  Synthesis of spirocyclic σ1 receptor ligands as potential PET radiotracers, structure–affinity relationships and in vitro metabolic stability

  摘要：

  Several 3H-spiro[[2] benzofuran-1,40-piperidines] bearing a p-fluorobenzyl residue at the N-atom and various substituents in position 3 of the benzofuran system were synthesized. The crucial reaction steps are the addition of a lithiated benzaldehyde derivative to the p-fluorobenzylpiperidone 5 and the BF3 center dot OEt2 catalyzed substitution of the methoxy group of 2a by various nucleophiles. Structure-affinity relationship studies revealed that compounds with two protons (2d), a methoxy group (2a), and a cyano group (2e) in position 3 possess subnanomolar sigma(1) affinity (K-i = 0.18 nM, 0.79 nM, 0.86 nM) and high selectivity against the sigma(2) subtype. The metabolites of 2a, 2d, and 2e, which were formed upon incubation with rat liver microsomes, were identified. Additionally, the rate of metabolic degradation of 2a, 2d, and 2e was determined and compared with the degradation rate of the non-fluorinated spirocyclic compound 1. For the synthesis of the potential PET tracers [F-18] 2a and [F-18]2e two different radiosynthetic approaches were followed. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.03.060
• 作为产物：
  描述：

  2-[1-(4-fluorobenzyl)-4-hydroxypiperidin-4-yl]benzaldehyde dimethyl acetal 在 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 反应 144.0h， 以54 mg的产率得到1'-(4-fluorobenzyl)-3-methoxy-3H-spiro[[2]benzofuran-1,4'-piperidine]
  参考文献：
  名称：

  Synthesis of spirocyclic σ1 receptor ligands as potential PET radiotracers, structure–affinity relationships and in vitro metabolic stability

  摘要：

  Several 3H-spiro[[2] benzofuran-1,40-piperidines] bearing a p-fluorobenzyl residue at the N-atom and various substituents in position 3 of the benzofuran system were synthesized. The crucial reaction steps are the addition of a lithiated benzaldehyde derivative to the p-fluorobenzylpiperidone 5 and the BF3 center dot OEt2 catalyzed substitution of the methoxy group of 2a by various nucleophiles. Structure-affinity relationship studies revealed that compounds with two protons (2d), a methoxy group (2a), and a cyano group (2e) in position 3 possess subnanomolar sigma(1) affinity (K-i = 0.18 nM, 0.79 nM, 0.86 nM) and high selectivity against the sigma(2) subtype. The metabolites of 2a, 2d, and 2e, which were formed upon incubation with rat liver microsomes, were identified. Additionally, the rate of metabolic degradation of 2a, 2d, and 2e was determined and compared with the degradation rate of the non-fluorinated spirocyclic compound 1. For the synthesis of the potential PET tracers [F-18] 2a and [F-18]2e two different radiosynthetic approaches were followed. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.03.060

文献信息

• Synthesis of spirocyclic σ1 receptor ligands as potential PET radiotracers, structure–affinity relationships and in vitro metabolic stability
  作者：Eva Große Maestrup、Christian Wiese、Dirk Schepmann、Achim Hiller、Steffen Fischer、Matthias Scheunemann、Peter Brust、Bernhard Wünsch

  DOI：10.1016/j.bmc.2009.03.060

  日期：2009.5

  Several 3H-spiro[[2] benzofuran-1,40-piperidines] bearing a p-fluorobenzyl residue at the N-atom and various substituents in position 3 of the benzofuran system were synthesized. The crucial reaction steps are the addition of a lithiated benzaldehyde derivative to the p-fluorobenzylpiperidone 5 and the BF3 center dot OEt2 catalyzed substitution of the methoxy group of 2a by various nucleophiles. Structure-affinity relationship studies revealed that compounds with two protons (2d), a methoxy group (2a), and a cyano group (2e) in position 3 possess subnanomolar sigma(1) affinity (K-i = 0.18 nM, 0.79 nM, 0.86 nM) and high selectivity against the sigma(2) subtype. The metabolites of 2a, 2d, and 2e, which were formed upon incubation with rat liver microsomes, were identified. Additionally, the rate of metabolic degradation of 2a, 2d, and 2e was determined and compared with the degradation rate of the non-fluorinated spirocyclic compound 1. For the synthesis of the potential PET tracers [F-18] 2a and [F-18]2e two different radiosynthetic approaches were followed. (C) 2009 Elsevier Ltd. All rights reserved.