1-(3-(2-fluoroethoxy)phenyl)piperazine | 1265157-04-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 1-(3-(2-fluoroethoxy)phenyl)piperazine
• 英文别名: 1-[3-(2-Fluoroethoxy)phenyl]-piperazine；1-[3-(2-fluoroethoxy)phenyl]piperazine
• CAS: 1265157-04-7
• 化学式: C₁₂H₁₇FN₂O
• 分子量: 224.278
• InChiKey: KSXIEEVJEHRVSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  24.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methanesulfonic acid 4-(2-oxo-2,3-dihydro-1H-indol-3-yl)butyl ester 、 1-(3-(2-fluoroethoxy)phenyl)piperazine 在 sodium carbonate 作用下， 以 neat (no solvent) 为溶剂， 反应 1.0h， 生成 ENL20
  参考文献：
  名称：

  Development and Evaluation of Two Potential 5-HT₇ Receptor PET Tracers: [¹⁸F]ENL09 and [¹⁸F]ENL10

  摘要：

  The latest addition to the serotonin (5-HT) receptor family is the 5-HT7 receptor (5-HT7R). This receptor has gained interest as a drug target due to its involvement in various disorders such as depression or schizophrenia. There is currently no clinically validated positron emission tomography (PET) tracer for the 5-HT7R available. But, the (arylpiperazinyl-butyl)oxindole scaffold provides a promising lead structure for this purpose. Here, we synthesized 12 (arylpiperazinyl-butyl)oxindole derivatives and in vitro affinity screening identified two structures with suitable affinity and selectivity to be radiolabeled and tested as 5-HT7R selective PET tracers. Next, the radiolabeled products [F-18]ENL09 and [F-18]ENL10 were evaluated as PET tracers in rats. Both tracers were found to be P-gp substrates, but after P-gp inhibition the brain uptake showed a regional distribution in line with the known 5-HT7R distribution. The [F-18]ENL10 brain binding was displaceable with a 5-HT7R selective ligand, whereas [F-18]ENL09 was not. We find that [F-18]ENL10 is a promising 5-HT7R selective PET tracer candidate that should be investigated in higher species.

  DOI：

  10.1021/acschemneuro.9b00132
• 作为产物：
  描述：

  1-(3-羟基苯基)-哌嗪-4-羧酸叔丁酯 在 potassium carbonate 、 三氟乙酸 、 sodium iodide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 生成 1-(3-(2-fluoroethoxy)phenyl)piperazine
  参考文献：
  名称：

  Novel indole-based sigma-2 receptor ligands: synthesis, structure–affinity relationship and antiproliferative activity

  摘要：

  小说sigma-2 配体1b在DU145细胞中诱导G1期细胞周期停滞并显示抗增殖活性。

  DOI：

  10.1039/c5md00079c

文献信息

• Synthesis of novel WAY 100635 derivatives containing a norbornene group and radiofluorination of [¹⁸F]AH1.MZ as a serotonin 5-HT_1Areceptor antagonist for molecular imaging
  作者：Matthias M. Herth、Vasko Kramer、Frank Rösch

  DOI：10.1002/jlcr.1589

  日期：2009.5.30

  5-HT1A receptors are involved in a variety of psychiatric disorders and in vivo molecular imaging of the 5-HT1A status represents an important approach to analyze and treat these disorders. We report herein the synthesis of three new fluoroethylated 5-HT1A ligands (AH1.MZ, AH2.MZ and AH3.MZ) as arylpiperazine derivatives containing a norbornene group. AH1.MZ (Ki= 4.2 nM) and AH2.MZ (Ki=30 nM) showed reasonable in vitro affinities to the 5-HT1A receptor, whereas AH3.MZ appeared to be non-affine toward the 5-HT1A receptor. The receptor profile of AH1.MZ and AH2.MZ showed selectivity within the 5-HT system. 18F-labelling via [18F]FETos to [18F]AH1.MZ was carried out in radiochemical yields of >70%. The final formulation of injectable solutions including [18F]FETos synthon synthesis, radiosynthesis and semi-preparative high-performance liquid chromatography (HPLC) separation took no longer than 130 min and provided [18F]AH1.MZ with a purity of  >98% as indicated by analytical HPLC analyses. Copyright © 2009 John Wiley & Sons, Ltd.

  5-HT1A受体参与多种精神疾病，活体分子影像学中5-HT1A状态的检测是分析和治疗这些疾病的重要方法。本文报道了三种新的含氟乙基的5-HT1A配体（AH1.MZ、AH2.MZ和AH3.MZ）的合成，它们是含有降冰片烯基团的苯基哌嗪衍生物。AH1.MZ（Ki=4.2nM）和AH2.MZ（Ki=30nM）对5-HT1A受体表现出合理的体外亲和力，而AH3.MZ似乎对5-HT1A受体没有亲和力。AH1.MZ和AH2.MZ的受体特征显示在5-HT系统内的选择性。通过[18F]FETos对[18F]AH1.MZ进行18F标记的放射化学产率>70%。注射液的最终配方包括[18F]FETos前体合成、放射合成和半制备高效液相色谱（HPLC）分离，整个过程不超过130分钟，并通过分析HPLC分析表明[18F]AH1.MZ的纯度>98%。版权所有 © 2009 John Wiley & Sons, Ltd.
• Development and Evaluation of Two Potential 5-HT₇ Receptor PET Tracers: [¹⁸F]ENL09 and [¹⁸F]ENL10
  作者：Elina Tampio L’Estrade、Mengfei Xiong、Vladimir Shalgunov、Fraser G. Edgar、Balázs Volk、Simone L. Baerentzen、Mikael Palner、Maria Erlandsson、Tomas Ohlsson、Gitte M. Knudsen、Matthias M. Herth

  DOI：10.1021/acschemneuro.9b00132

  日期：2019.9.18

  The latest addition to the serotonin (5-HT) receptor family is the 5-HT7 receptor (5-HT7R). This receptor has gained interest as a drug target due to its involvement in various disorders such as depression or schizophrenia. There is currently no clinically validated positron emission tomography (PET) tracer for the 5-HT7R available. But, the (arylpiperazinyl-butyl)oxindole scaffold provides a promising lead structure for this purpose. Here, we synthesized 12 (arylpiperazinyl-butyl)oxindole derivatives and in vitro affinity screening identified two structures with suitable affinity and selectivity to be radiolabeled and tested as 5-HT7R selective PET tracers. Next, the radiolabeled products [F-18]ENL09 and [F-18]ENL10 were evaluated as PET tracers in rats. Both tracers were found to be P-gp substrates, but after P-gp inhibition the brain uptake showed a regional distribution in line with the known 5-HT7R distribution. The [F-18]ENL10 brain binding was displaceable with a 5-HT7R selective ligand, whereas [F-18]ENL09 was not. We find that [F-18]ENL10 is a promising 5-HT7R selective PET tracer candidate that should be investigated in higher species.
• Novel indole-based sigma-2 receptor ligands: synthesis, structure–affinity relationship and antiproliferative activity
  作者：Fang Xie、Torsten Kniess、Christin Neuber、Winnie Deuther-Conrad、Constantin Mamat、Brian P. Lieberman、Boli Liu、Robert H. Mach、Peter Brust、Jörg Steinbach、Jens Pietzsch、Hongmei Jia

  DOI：10.1039/c5md00079c

  日期：——

  Novel sigma-2 ligand 1b induced G₁ phase cell cycle arrest in DU145 cells and displayed antiproliferative activity.

  小说sigma-2 配体1b在DU145细胞中诱导G1期细胞周期停滞并显示抗增殖活性。