3H-spiro[[2]benzofuran-1,4'-piperidine]-3-carbonitrile | 1167435-02-0

• 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: 3H-spiro[[2]benzofuran-1,4'-piperidine]-3-carbonitrile
• CAS: 1167435-02-0
• 化学式: C₁₃H₁₄N₂O
• 分子量: 214.267
• InChiKey: AYZFHFORHJTYJF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.86
• 重原子数：
  16.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  45.05
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3H-spiro[[2]benzofuran-1,4'-piperidine]-3-carbonitrile 、 对氟苯甲醛 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 以20%的产率得到1'-(4-fluorobenzyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]-3-carbonitrile
  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：

  1'-Benzyl-3H-spiro[isobenzofuran-1,4'-piperidine]-3-carbonitrile 在 10% palladium on carbon 、 甲酸铵 作用下， 以 甲醇 为溶剂， 反应 8.0h， 生成 3H-spiro[[2]benzofuran-1,4'-piperidine]-3-carbonitrile
  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