6-(4-[4-[¹⁸F]fluoro-3-hydroxybenzyl]piperazine-1-yl)benzodioxin | 1350900-77-4

• 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: 6-(4-[4-[¹⁸F]fluoro-3-hydroxybenzyl]piperazine-1-yl)benzodioxin
• 英文别名: 5-[[4-(2,3-dihydro-1,4-benzodioxin-6-yl)piperazin-1-yl]methyl]-2-(18F)fluoranylphenol
• CAS: 1350900-77-4
• 化学式: C₁₉H₂₁FN₂O₃
• 分子量: 343.387
• InChiKey: SXICCGPFVRVNMD-LRFGSCOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  45.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  6-氨基-1,4-苯并二氧杂环 在 甲酸铵 、 sodium cyanoborohydride 、 钯 作用下， 以 甲醇 、 乙二醇 、 溶剂黄146 、 二甲基亚砜 为溶剂， 反应 0.38h， 生成 6-(4-[4-[¹⁸F]fluoro-3-hydroxybenzyl]piperazine-1-yl)benzodioxin
  参考文献：
  名称：

  用氟 18 标记苯二恶英哌嗪作为多巴胺 D4 受体选择性成像的前瞻性放射性配体

  摘要：

  D(4) 受体对研究和临床应用具有很高的兴趣，但对合适的放射配体提出了很高的要求，以使其成为有用的调查工具。因此，寻找适合体内成像的足够放射性配体仍在进行中。潜在的精神安定药物 6-(4-[4-fluorobenzyl]piperazin-1-yl)benzodioxin 对 D(4) 受体显示出高亲和力和选择性。通过添加亲水性部分对这种先导结构进行衍生化，以降低其亲脂性，这导致了三个新的假定多巴胺受体 D(4) 配体。给出了以令人满意的产率获得的标准化合物和相应标记前体的合成的综合描述。此外，还比较了通过直接 (18) F 标记和累积合成进行的放射合成。

  DOI：

  10.1002/jlcr.3074

文献信息

• Evaluation of ¹⁸F-Labeled Benzodioxine Piperazine-Based Dopamine D₄ Receptor Ligands: Lipophilicity as a Determinate of Nonspecific Binding
  作者：Fabian Kügler、Wiebke Sihver、Johannes Ermert、Harald Hübner、Peter Gmeiner、Olaf Prante、Heinz H. Coenen

  DOI：10.1021/jm200762g

  日期：2011.12.22

  Derivatization of the putative neuroleptic 1-(2,3-dihydrobenzo[1,4]dioxin-6-yl)-4-(4-fluorobenzyl)-piperazine (3a) led to a series of new dopamine receptor D-4 ligands displaying high affinity (K-i = 1.1-15 nM) and D-2/D-4 subtype selectivities of about 800-6700. These ligands were labeled with the short-lived positron emitter fluorine-18 and analyzed for their potential application for imaging studies by positron emission tomography (PET). In vitro autoradiography was used to determine their nonspecific binding behavior as a result of their structural and thus physicochemical properties. The biodistribution, in vivo stability, and brain uptake of the most promising D-4 radioligand candidate were determined. This proved to be 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-4-((6-fluoropyridin-3-yl)methyl)piperazine ([F-18]3d), which revealed an excellent binding pattern with a high selectivity and limited nonspecific binding in vitro. This analogue also exhibited a high stability and an extremely high brain uptake in vivo with specific binding in hippocampus, cortex, colliculus, and cerebellum as determined by ex vivo autoradiography. Thus, [F-18]3d appears as a suitable D-4 radioligand for in vivo imaging, encouraging continued evaluation by PET studies.
• Labeling of benzodioxin piperazines with fluorine-18 as prospective radioligands for selective imaging of dopamine D₄receptors
  作者：Fabian Kügler、Johannes Ermert、Heinz H. Coenen

  DOI：10.1002/jlcr.3074

  日期：2013.10

  lipophilicity what led to three new putative dopamine receptor D(4) ligands. A comprehensive description of the syntheses of standard compounds and corresponding labeling precursors is given which were obtained in satisfactory yields. Furthermore, the radiosyntheses by direct (18) F-labeling and build-up synthesis were compared. All derivatives of 6-(4-[4-fluorobenzyl]-piperazin-1-yl)benzodioxin were

  D(4) 受体对研究和临床应用具有很高的兴趣，但对合适的放射配体提出了很高的要求，以使其成为有用的调查工具。因此，寻找适合体内成像的足够放射性配体仍在进行中。潜在的精神安定药物 6-(4-[4-fluorobenzyl]piperazin-1-yl)benzodioxin 对 D(4) 受体显示出高亲和力和选择性。通过添加亲水性部分对这种先导结构进行衍生化，以降低其亲脂性，这导致了三个新的假定多巴胺受体 D(4) 配体。给出了以令人满意的产率获得的标准化合物和相应标记前体的合成的综合描述。此外，还比较了通过直接 (18) F 标记和累积合成进行的放射合成。