4-((3H-spiro[2-benzofuran-1,4′-piperidine]-1′-yl)methyl)phenol | 1396802-70-2

• 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: 4-((3H-spiro[2-benzofuran-1,4′-piperidine]-1′-yl)methyl)phenol
• 英文别名: 4-(spiro[1H-2-benzofuran-3,4'-piperidine]-1'-ylmethyl)phenol
• CAS: 1396802-70-2
• 化学式: C₁₉H₂₁NO₂
• 分子量: 295.381
• InChiKey: MMGHAYFIVKJIMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-((3H-spiro[2-benzofuran-1,4′-piperidine]-1′-yl)methyl)phenol 在 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 、 氢氟酸 作用下， 以 水 、 乙腈 为溶剂， 反应 12.08h， 生成 C₂₁H₂₄⁽¹⁸⁾FNO₂
  参考文献：
  名称：

  Synthesis and Evaluation of Novel ¹⁸F-Labeled Spirocyclic Piperidine Derivatives as σ₁ Receptor Ligands for Positron Emission Tomography Imaging

  摘要：

  A series of spirocyclic piperidine derivatives were designed and synthesized as sigma(1) receptor ligands. In vitro competition binding assays showed that 1'-(4-(2-fluoroethoxy)benzyl)-3H-spiro[2-benzofuran-1,4'-pipericline] (19) possessed high sigma(1) receptor affinity (K-i = 0.79 nM) and excellent sigma(1)/sigma(2) subtype selectivity (350-fold) as well as high sigma(1)/VAChT selectivity (799-fold). The radiolabeled compound [F-18]19 was synthesized by substitution of the tosylate precursor 24 with [F-18]fluoride, with an isolated radiochemical yield of 35-60%, a radiochemical purity of >99%, and a specific activity of 30-55 GBq/mu mol. Biodistribution studies in imprinting control region mice indicated that [F-18] 19 displayed excellent initial brain uptake and slow washout. Ex vivo autoradiography in Sprague Dawley rats demonstrated high accumulation of the radiotracer in brain areas known to express high levels of sigma(1) receptors. Micro positron emission tomography imaging and blocking studies confirmed the specific binding of [F-18] 19 to sigma(1) receptors in vivo.

  DOI：

  10.1021/jm301734g
• 作为产物：
  描述：

  3H-螺[2-苯并呋喃-1,4'-哌啶] 、 对羟基苯甲醛 在 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 8.0h， 以69%的产率得到4-((3H-spiro[2-benzofuran-1,4′-piperidine]-1′-yl)methyl)phenol
  参考文献：
  名称：

  合成和评价18作为有前途的σF-标记的螺哌啶衍生物1个受体显像剂

  摘要：

  几个螺哌啶衍生物，设计并为σ合成1受体配体。体外竞争结合测定显示，与小取代基氟代类似物具有朝向σ高亲和力1受体和亚型选择性。特别是用于配体1' - （（6-（2-氟乙氧基）吡啶-3-基）甲基）-3- ħ -螺[2-苯并呋喃-1,4'-哌啶]（2），高σ 1个受体亲和力（ķ我 = 2.30 1nM）和高σ 1 /σ 2亚型选择性（以及高σ142倍）1 /倍234观察中VAChT选择性（）。[ 18楼] 2是在自制的自动合成模块中使用高效的一锅两步反应方法合成的，总的分离放射化学产率为8-10％，放射化学纯度高于99％，比活度为56- 78 GBq /μmol。[ 18 F] 2在ICR小鼠中的生物分布研究表明，高的初始大脑摄取和相对较快的冲刷。氟哌啶醇，化合物的给药1和[注射之前（微摩尔/ kg的3,5，或10）5分钟，以不同浓度的SA4503的18 F] 2显著降低在已知含有σ器官的放射性

  DOI：

  10.1016/j.bmc.2014.08.003

文献信息

• Synthesis and Evaluation of Novel ¹⁸F-Labeled Spirocyclic Piperidine Derivatives as σ₁ Receptor Ligands for Positron Emission Tomography Imaging
  作者：Yan Li、Xia Wang、Jinming Zhang、Winnie Deuther-Conrad、Fang Xie、Xiaojun Zhang、Jian Liu、Jinping Qiao、Mengchao Cui、Jörg Steinbach、Peter Brust、Boli Liu、Hongmei Jia

  DOI：10.1021/jm301734g

  日期：2013.5.9

  A series of spirocyclic piperidine derivatives were designed and synthesized as sigma(1) receptor ligands. In vitro competition binding assays showed that 1'-(4-(2-fluoroethoxy)benzyl)-3H-spiro[2-benzofuran-1,4'-pipericline] (19) possessed high sigma(1) receptor affinity (K-i = 0.79 nM) and excellent sigma(1)/sigma(2) subtype selectivity (350-fold) as well as high sigma(1)/VAChT selectivity (799-fold). The radiolabeled compound [F-18]19 was synthesized by substitution of the tosylate precursor 24 with [F-18]fluoride, with an isolated radiochemical yield of 35-60%, a radiochemical purity of >99%, and a specific activity of 30-55 GBq/mu mol. Biodistribution studies in imprinting control region mice indicated that [F-18] 19 displayed excellent initial brain uptake and slow washout. Ex vivo autoradiography in Sprague Dawley rats demonstrated high accumulation of the radiotracer in brain areas known to express high levels of sigma(1) receptors. Micro positron emission tomography imaging and blocking studies confirmed the specific binding of [F-18] 19 to sigma(1) receptors in vivo.
• Synthesis and evaluation of a 18F-labeled spirocyclic piperidine derivative as promising σ1 receptor imaging agent
  作者：Yuan-Yuan Chen、Xia Wang、Jin-Ming Zhang、Winnie Deuther-Conrad、Xiao-Jun Zhang、Yiyun Huang、Yan Li、Jia-Jun Ye、Meng-Chao Cui、Jörg Steinbach、Peter Brust、Bo-Li Liu、Hong-Mei Jia

  DOI：10.1016/j.bmc.2014.08.003

  日期：2014.10

  Several spirocyclic piperidine derivatives were designed and synthesized as σ1 receptor ligands. In vitro competition binding assays showed that the fluoroalkoxy analogues with small substituents possessed high affinity towards σ1 receptors and subtype selectivity. Particularly for ligand 1′-((6-(2-fluoroethoxy)pyridin-3-yl)methyl)-3H-spiro[2-benzofuran-1,4′-piperidine] (2), high σ1 receptor affinity

  几个螺哌啶衍生物，设计并为σ合成1受体配体。体外竞争结合测定显示，与小取代基氟代类似物具有朝向σ高亲和力1受体和亚型选择性。特别是用于配体1' - （（6-（2-氟乙氧基）吡啶-3-基）甲基）-3- ħ -螺[2-苯并呋喃-1,4'-哌啶]（2），高σ 1个受体亲和力（ķ我 = 2.30 1nM）和高σ 1 /σ 2亚型选择性（以及高σ142倍）1 /倍234观察中VAChT选择性（）。[ 18楼] 2是在自制的自动合成模块中使用高效的一锅两步反应方法合成的，总的分离放射化学产率为8-10％，放射化学纯度高于99％，比活度为56- 78 GBq /μmol。[ 18 F] 2在ICR小鼠中的生物分布研究表明，高的初始大脑摄取和相对较快的冲刷。氟哌啶醇，化合物的给药1和[注射之前（微摩尔/ kg的3,5，或10）5分钟，以不同浓度的SA4503的18 F] 2显著降低在已知含有σ器官的放射性