[18F]-3-benzyloxy-4-fluorobenzaldehyde | 347176-77-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: [18F]-3-benzyloxy-4-fluorobenzaldehyde
• 英文别名: 4-(18F)fluoranyl-3-phenylmethoxybenzaldehyde
• CAS: 347176-77-6
• 化学式: C₁₄H₁₁FO₂
• 分子量: 229.24
• InChiKey: SJTDGEBYNOHSTC-HUYCHCPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [18F]-3-benzyloxy-4-fluorobenzaldehyde 在 ammonium formate 、 钯 作用下， 生成
  参考文献：
  名称：

  Evaluation of ¹⁸F-Labeled Benzodioxine Piperazine-Based Dopamine D₄ Receptor Ligands: Lipophilicity as a Determinate of Nonspecific Binding

  摘要：

  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.

  DOI：

  10.1021/jm200762g
• 作为产物：
  描述：

  3-benzyloxy-4-N,N-dimethylaminobenzaldehyde 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 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 7.0h， 生成 [18F]-3-benzyloxy-4-fluorobenzaldehyde
  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

• Synthesis of high-specific-radioactivity 4- and 6-[18F]fluorometaraminol- PET tracers for the adrenergic nervous system of the heart
  作者：Oliver Langer、Frédéric Dollé、Héric Valette、Christer Halldin、Françoise Vaufrey、Chantal Fuseau、Christine Coulon、Michéle Ottaviani、Kjell Någren、Michel Bottlaender、Bernard Maziére、Christian Crouzel

  DOI：10.1016/s0968-0896(00)00286-8

  日期：2001.3

  enantiomers. Secondly, the corresponding 6-fluoro analogues, fluorine-18-labeled 6-fluorometaraminol (6-[18F]FMR or (1R,2S)-2-amino-1-(2-[18F]fluoro-5-hydroxyphenyl)-1-propanol) and its three other enantiomers, were prepared in an analogous way. Typically, 0.48-0.55 GBq of 4-[18F]FMR and 0.14-0.15 GBq of 6-[18F]FMR could be obtained after 120-160 min total synthesis time, with a specific radioactivity of

  先前已发现氟18（t（1/2）109.8分钟）和碳11（t（1/2）20.4分钟）标记的去甲肾上腺素类似物可用于正电子发射断层扫描（PET）放射性配体以作图心脏的肾上腺神经末梢。间氨基（（1R，2S）-2-氨基-1-（3-羟基苯基）-1-丙醇）是去甲肾上腺素的代谢稳定结构类似物，对去甲肾上腺素转运蛋白和囊泡单胺转运蛋白具有高亲和力。本文介绍了高比放射性标记的新的正氨基发射正电子发射断层照相术卤代类似物的放射合成。首先，用氟18标记的4-氟甲基戊胺（4- [18F] FMR或（1R，2S）-2-氨基-1-（4- [18F]氟-3-羟基苯基）-1-丙醇）及其三个其他立体异构体是根据以下关键步骤制备的：（a）相应的无载体添加的标记的氟苯甲醛与硝基乙烷的缩合，以及（b）非对映体产物混合物的HPLC（C18和手性）拆分为四个单独的对映体。其次，相应的6-氟类似物，氟-18标记的6-氟甲基氨基（6- [18F]
• Synthesis and bioevaluation of [18F]4-fluoro-m-hydroxyphenethylguanidine ([18F]4F-MHPG): A novel radiotracer for quantitative PET studies of cardiac sympathetic innervation
  作者：Keun Sam Jang、Yong-Woon Jung、Phillip S. Sherman、Carole A. Quesada、Guie Gu、David M. Raffel

  DOI：10.1016/j.bmcl.2013.01.106

  日期：2013.3

  A new cardiac sympathetic nerve imaging agent, [F-18]4-fluoro-m-hydroxyphenethylguanidine ([F-18]4F-MHPG), was synthesized and evaluated. The radiosynthetic intermediate [F-18]4-fluoro-m-tyramine ([F-18]4F-MTA) was prepared and then sequentially reacted with cyanogen bromide and NH4Br/NH4OH to afford [F-18]4F-MHPG. Initial bioevaluations of [F-18]4F-MHPG (biodistribution studies in rats and kinetic studies in the isolated rat heart) were similar to results previously reported for the carbon-11 labeled analog [C-11]4F-MHPG. The neuronal uptake rate of [F-18]4F-MHPG into the isolated rat heart was 0.68 ml/min/g wet and its retention time in sympathetic neurons was very long (T-1/2 > 13 h). A PET imaging study in a nonhuman primate with [F-18]4F-MHPG provided high quality images of the heart, with heart-to-blood ratios at 80-90 min after injection of 5-to-1. These initial kinetic and imaging studies of [F-18]4F-MHPG suggest that this radiotracer may allow for more accurate quantification of regional cardiac sympathetic nerve density than is currently possible with existing neuronal imaging agents. (C) 2013 Elsevier Ltd. All rights reserved.
• Langer; Dolle; Halldin, Journal of labelled compounds and radiopharmaceuticals, 1999, vol. 42, # SUPPL. 1, p. S504-S506
  作者：Langer、Dolle、Halldin、Vaufrey、Coulon、Fuseau、Bottlaender、Crouzel

  DOI：——

  日期：——
• 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。
• 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.