4-(4-(2-(2-fluoroethoxy))phenylpiperazin-1-yl)butan-1-amine | 1138217-76-1

• 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: 4-(4-(2-(2-fluoroethoxy))phenylpiperazin-1-yl)butan-1-amine
• 英文别名: 4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butan-1-amine；4-(2-(2-fluoroethoxy)phenyl)-1-piperazinebutanamine；4-[4-[2-(2-Fluoroethoxy)phenyl]piperazin-1-yl]butan-1-amine
• CAS: 1138217-76-1
• 化学式: C₁₆H₂₆FN₃O
• 分子量: 295.4
• InChiKey: NRRAQOQTPZTHLL-UHFFFAOYSA-N

物化性质

• 沸点：
  433.3±45.0 °C(predicted)
• 密度：
  1.082±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  41.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(3-噻吩基)苯甲酸 、 4-(4-(2-(2-fluoroethoxy))phenylpiperazin-1-yl)butan-1-amine 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 以62%的产率得到4-(thiophen-3-yl)-N-(4-(4-(2-(2-fluoroethoxy)phenyl)piperazin-1-yl)butyl)benzamide
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of Fluorine-Containing D₃ Dopamine Receptor Ligands

  摘要：

  A series of fluorine-containing N-(2-methoxyphenyl)piperazine and N-(2-fluoroethoxy)piperazine analogues were synthesized, and their affinities for human dopamine D-2, D-3, and D-4 receptors were determined. Radioligand binding studies identified five compounds, 18a, 20a, 20c, 20e, and 21e, which bind with high affinity at D-3 (K-i = 0.17-5 nM) and moderate to high selectivity for D-3 VS D-2 receptors (ranging from similar to 25-to 163-fold). These compounds were also evaluated for intrinsic activity at D-2 and D3 receptors using a forskolin-dependent adenylyl cyclase assay. This panel of compounds exhibits varying receptor subtype binding selectivity and intrinsic activity at D-2 VS D-3 receptors. These compounds may be useful for behavioral pharmacology studies on the role of D-2-like dopamine receptors in neuropsychiatric and neurological disorders. Furthermore, compound 20e, which has the highest binding affinity and selectivity for the D-3 receptor (K-i = 0.17 nM for D-3, 163-fold selectivity for D-3 VS D-2 receptors), represents a candidate fluorine-18 radiotracer for in vivo PET imaging studies on the regulation of D-3 receptor expression.

  DOI：

  10.1021/jm101323b
• 作为产物：
  描述：

  1-(2-羟基苯基)哌嗪 在 potassium carbonate 、 三乙胺 、 肼 作用下， 以 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 20.0h， 生成 4-(4-(2-(2-fluoroethoxy))phenylpiperazin-1-yl)butan-1-amine
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of Fluorine-Containing D₃ Dopamine Receptor Ligands

  摘要：

  A series of fluorine-containing N-(2-methoxyphenyl)piperazine and N-(2-fluoroethoxy)piperazine analogues were synthesized, and their affinities for human dopamine D-2, D-3, and D-4 receptors were determined. Radioligand binding studies identified five compounds, 18a, 20a, 20c, 20e, and 21e, which bind with high affinity at D-3 (K-i = 0.17-5 nM) and moderate to high selectivity for D-3 VS D-2 receptors (ranging from similar to 25-to 163-fold). These compounds were also evaluated for intrinsic activity at D-2 and D3 receptors using a forskolin-dependent adenylyl cyclase assay. This panel of compounds exhibits varying receptor subtype binding selectivity and intrinsic activity at D-2 VS D-3 receptors. These compounds may be useful for behavioral pharmacology studies on the role of D-2-like dopamine receptors in neuropsychiatric and neurological disorders. Furthermore, compound 20e, which has the highest binding affinity and selectivity for the D-3 receptor (K-i = 0.17 nM for D-3, 163-fold selectivity for D-3 VS D-2 receptors), represents a candidate fluorine-18 radiotracer for in vivo PET imaging studies on the regulation of D-3 receptor expression.

  DOI：

  10.1021/jm101323b

文献信息

• Synthesis and in vitro pharmacological evaluation of indolyl carboxylic amide analogues as D3 dopamine receptor selective ligands
  作者：Zhude Tu、Shihong Li、Aixiao Li、Michelle Taylor、David Ho、Maninder Malik、Robert R. Luedtke、Robert H. Mach

  DOI：10.1039/c3md00098b

  日期：——

  A series of substituted 1H-indolyl carboxylic acid amides that contain a N-(2-methoxyphenyl)piperazine or N-(2-fluoroethoxy)piperazine group were synthesized and their affinities for human dopamine D2, D3, and D4 receptors were determined. Two of these compounds, 14a and 14b, displayed high binding affinity at D3 (Ki = 0.18 and 0.4 nM, respectively), and selectivity for D3vs. D2 receptors (87-fold and 60-fold, respectively). These two compounds had low binding affinity at D4 receptors and σ receptor sites. The intrinsic activity of these compounds at D2 and D3 receptors was determined using a forskolin-dependent adenylyl cyclase inhibition assay; both 14a and 14b were found to be partial agonists. Furthermore, for compound 14a, the log D value of 2.85 suggested it has suitable lipophilicity for crossing the blood–brain-barrier.

  合成了一系列取代的1H-吲哚羧酸酰胺，这些化合物包含N-(2-甲氧基苯基)哌嗪或N-(2-氟乙氧基)哌嗪基团，并确定了它们对人类多巴胺D2、D3和D4受体的亲和力。其中两个化合物，14a和14b，在D3受体上显示出高结合亲和力（Ki分别为0.18和0.4 nM），并且在D3与D2受体之间具有选择性（分别为87倍和60倍）。这两个化合物在D4受体和σ受体位点的结合亲和力较低。通过使用依赖于福斯可林的腺苷酸酰化酶抑制测定，确定了这些化合物在D2和D3受体上的内在活性；发现14a和14b都是部分激动剂。此外，对于化合物14a，其log D值为2.85，表明其具有适合穿越血脑屏障的脂溶性。
• Synthesis and Pharmacological Evaluation of Fluorine-Containing D₃ Dopamine Receptor Ligands
  作者：Zhude Tu、Shihong Li、Jinquan Cui、Jinbin Xu、Michelle Taylor、David Ho、Robert R. Luedtke、Robert H. Mach

  DOI：10.1021/jm101323b

  日期：2011.3.24

  A series of fluorine-containing N-(2-methoxyphenyl)piperazine and N-(2-fluoroethoxy)piperazine analogues were synthesized, and their affinities for human dopamine D-2, D-3, and D-4 receptors were determined. Radioligand binding studies identified five compounds, 18a, 20a, 20c, 20e, and 21e, which bind with high affinity at D-3 (K-i = 0.17-5 nM) and moderate to high selectivity for D-3 VS D-2 receptors (ranging from similar to 25-to 163-fold). These compounds were also evaluated for intrinsic activity at D-2 and D3 receptors using a forskolin-dependent adenylyl cyclase assay. This panel of compounds exhibits varying receptor subtype binding selectivity and intrinsic activity at D-2 VS D-3 receptors. These compounds may be useful for behavioral pharmacology studies on the role of D-2-like dopamine receptors in neuropsychiatric and neurological disorders. Furthermore, compound 20e, which has the highest binding affinity and selectivity for the D-3 receptor (K-i = 0.17 nM for D-3, 163-fold selectivity for D-3 VS D-2 receptors), represents a candidate fluorine-18 radiotracer for in vivo PET imaging studies on the regulation of D-3 receptor expression.