1'-(4-fluorobenzyl)-3-(3-fluoropropyl)-3H-spiro[[2]benzofuran-1,4'-piperidine] | 1189530-53-7

• 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-(3-fluoropropyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]
• 英文别名: 1'-[(4-fluorophenyl)methyl]-1-(3-fluoropropyl)spiro[1H-2-benzofuran-3,4'-piperidine]
• CAS: 1189530-53-7
• 化学式: C₂₂H₂₅F₂NO
• 分子量: 357.443
• InChiKey: VCRRGVDRNWQLNT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-(3-fluoropropyl)-3H-spiro[[2]benzofuran-1,4'-piperidine] 、 4-氟氯苄 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 以71%的产率得到1'-(4-fluorobenzyl)-3-(3-fluoropropyl)-3H-spiro[[2]benzofuran-1,4'-piperidine]
  参考文献：
  名称：

  Evaluation of Spirocyclic 3-(3-Fluoropropyl)-2-benzofurans as σ₁ Receptor Ligands for Neuroimaging with Positron Emission Tomography

  摘要：

  A series of various N-substituted 3-(3-fluoropropyl)-3H-spiro[[2]benzofuran-1,4'-piperidines] (7) has been synthesized. In receptor binding studies, the N-benzyl derivative 7a (WMS-1813) revealed extraordinarily high sigma(1) receptor affinity (K-i = 1.4 nM) and excellent sigma(1)/sigma(2) Selectivity (>600fold). In vitro biotransformation of 7a with rat liver microsomes led to three main metabolites. N-Debenzylation was inhibited by introduction of an N-phenylethyl residue (7g). The PET tracer [F-18]7a was synthesized by nucleophilic substitution of the tosylate 13 with K[F-18]F-K222-carbonate complex. The decay corrected radiochemical yield of [F-18]7a was 35-48% with a radiochemical purity of >99.5% and a specific activity of 150-238 GBq/mu mol. The radiotracer properties were evaluated in female CD-1 mice by organ distribution and ex vivo brain autoradiography. The radiotracer uptake in the brain was fast and sufficient, with values of similar to 4% injected dose per gram. Target specificity of [F-18]7a was validated in blocking studies by preapplication of haloperidol, and significant reduction in the uptake of radioactivity was observed in the brain and peripheral organs expressing sigma(1) receptors.

  DOI：

  10.1021/jm900909e

文献信息

• Evaluation of Spirocyclic 3-(3-Fluoropropyl)-2-benzofurans as σ₁ Receptor Ligands for Neuroimaging with Positron Emission Tomography
  作者：Eva Große Maestrup、Steffen Fischer、Christian Wiese、Dirk Schepmann、Achim Hiller、Winnie Deuther-Conrad、Jörg Steinbach、Bernhard Wünsch、Peter Brust

  DOI：10.1021/jm900909e

  日期：2009.10.8

  A series of various N-substituted 3-(3-fluoropropyl)-3H-spiro[[2]benzofuran-1,4'-piperidines] (7) has been synthesized. In receptor binding studies, the N-benzyl derivative 7a (WMS-1813) revealed extraordinarily high sigma(1) receptor affinity (K-i = 1.4 nM) and excellent sigma(1)/sigma(2) Selectivity (>600fold). In vitro biotransformation of 7a with rat liver microsomes led to three main metabolites. N-Debenzylation was inhibited by introduction of an N-phenylethyl residue (7g). The PET tracer [F-18]7a was synthesized by nucleophilic substitution of the tosylate 13 with K[F-18]F-K222-carbonate complex. The decay corrected radiochemical yield of [F-18]7a was 35-48% with a radiochemical purity of >99.5% and a specific activity of 150-238 GBq/mu mol. The radiotracer properties were evaluated in female CD-1 mice by organ distribution and ex vivo brain autoradiography. The radiotracer uptake in the brain was fast and sufficient, with values of similar to 4% injected dose per gram. Target specificity of [F-18]7a was validated in blocking studies by preapplication of haloperidol, and significant reduction in the uptake of radioactivity was observed in the brain and peripheral organs expressing sigma(1) receptors.