7-{2-[2-(2-[18F]fluoroethoxy)ethoxy]ethoxy}-1-methyl-9H-β-carboline | 1118607-62-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: 7-{2-[2-(2-[18F]fluoroethoxy)ethoxy]ethoxy}-1-methyl-9H-β-carboline
• 英文别名: 7-[2-[2-(2-(18F)fluoranylethoxy)ethoxy]ethoxy]-1-methyl-9H-pyrido[3,4-b]indole
• CAS: 1118607-62-7
• 化学式: C₁₈H₂₁FN₂O₃
• 分子量: 331.376
• InChiKey: JRVWNJFRMVDDMB-AWDFDDCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  56.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  哈尔酚 在 potassium [¹⁸F]fluoride 、 四丁基氟化铵 、 potassium carbonate 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 作用下， 以 四氢呋喃 、 二甲基亚砜 、 丙酮 、 乙腈 为溶剂， 反应 3.08h， 生成 7-{2-[2-(2-[18F]fluoroethoxy)ethoxy]ethoxy}-1-methyl-9H-β-carboline
  参考文献：
  名称：

  Selective binding to monoamine oxidase A: In vitro and in vivo evaluation of 18F-labeled β-carboline derivatives

  摘要：

  In this study we synthesized four different F-18-labeling precursors for the visualization of the monoamino oxidase A using harmol derivatives. Whereas two are for prosthetic group labeling using [F-18]fluoro-d(2)-methyl tosylate and 2-[F-18]fluoroethyl-tosylate, the other three precursors are for direct nucleophilic F-18-labeling. Additionally the corresponding reference compounds were synthesized. The syntheses of [F-18]fluoro-d(2)-methyl-harmol and 2-[F-18] fluoroethyl-harmol were carried out using harmol as starting material. For direct nucleophilic F-18-labeling of the tracers carrying oligoethyled spacers (PEG), a toluenesulfonyl leaving group was employed. The radiolabeling, purification and formulation for each tracer was optimized and evaluated in vitro and in vivo. Stability tests in human serum showed that all tracers were stable over the observation period of 60 min. mu PET studies using of the synthesized tracers revealed that the tracers carrying PEG spacers showed no sufficient brain uptake. Consequently, the F-18-fuoro alkylated tracers [F-18] fluoro-d2-methyl-harmol and 2-[F-18]fluoroethyl-harmol were further evaluated showing SUVs in the brain of 1.0 +/- 0.2 g/mL and 3.4 +/- 0.5 g/mL after 45 min, respectively. In blockade studies the selectivity and specificity of both tracers were demonstrated. However, for [F-18]fluoro-d(2)-methyl-harmol a rapid washout from the brain was also observed. In vitro binding assays revealed that 2-[F-18] fluoroethyl-harmol (IC50 = 0.54 +/- 0.06 nM) has a higher affinity than the F-18-fluoro-d(2)-methylated ligand (IC50 = 12.2 +/- 0.6 nM), making 2-[F-18] fluoroethyl-harmol superior to the other evaluated compounds and a promising tracer for PET imaging of the MAO A. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.11.040

文献信息

• Synthesis andin vitro evaluation of18F-β-carboline alkaloids as PET ligands
  作者：Elisabeth Blom、Farhad Karimi、Olof Eriksson、Håkan Hall、Bengt Långström

  DOI：10.1002/jlcr.1519

  日期：2008.5

  A one-step 18F-labelling strategy was used to prepare four 18F-labelled analogues of 7-methoxy-1-methyl-9H-β-carboline (harmine): 7-(2-[18F]fluoroethoxy)-1-methyl-9H-β-carboline (5), 7-(3-[18F]fluoro-propoxy)-1-methyl-9H-β-carboline (6), 7-[2-(2-[18F]fluoroethoxy)ethoxy]-1-methyl-9H-β-carboline (7), and 7-2-[2-(2-[18F]fluoroethoxy)ethoxy]-ethoxy}-1-methyl-9H-β-carboline (8). These were synthesized as potential positron emission tomography ligands for monoamine oxidase A (MAO-A). A solution of pure labelled compound in buffer was obtained in <70 min from end of radionuclide production, with a decay-corrected yield of up to 23%. The average specific binding to MAO-A in rat brain, determined by autoradiography experiments, was highest for compounds 7 and 8 (89±2 and 96±1%, respectively), which was obtained at <1 nM radioligand concentration. Copyright © 2008 John Wiley & Sons, Ltd.

  采用一步 18F 标记策略制备了四种 18F 标记的 7-甲氧基-1-甲基-9H-β-咔啉（harmine）类似物：7-(2-[18F]fluoroethoxy)-1-methyl-9H-β-carboline (5), 7-(3-[18F]fluoro-propoxy)-1-methyl-9H-β-carboline (6), 7-[2-(2-[18F]fluoroethoxy)ethoxy]-1-methyl-9H-β-carboline (7), and 7-2-[2-(2-[18F]fluoroethoxy)ethoxy]-ethoxy}-1-methyl-9H-β-carboline (8).这些化合物是作为单胺氧化酶 A（MAO-A）的潜在正电子发射断层扫描配体合成的。从放射性核素生产结束算起，在 70 分钟内就能得到缓冲液中的纯标记化合物溶液，衰变校正产率高达 23%。通过自显影实验测定，化合物 7 和 8 与大鼠大脑中 MAO-A 的平均特异性结合率最高（分别为 89±2% 和 96±1%），在放射性配体浓度小于 1 nM 时即可获得。Copyright © 2008 John Wiley & Sons, Ltd. All Rights Reserved.
• Selective binding to monoamine oxidase A: In vitro and in vivo evaluation of 18F-labeled β-carboline derivatives
  作者：Hanno Schieferstein、Markus Piel、Friderike Beyerlein、Hartmut Lüddens、Nicole Bausbacher、Hans-Georg Buchholz、Tobias L. Ross、Frank Rösch

  DOI：10.1016/j.bmc.2014.11.040

  日期：2015.2

  In this study we synthesized four different F-18-labeling precursors for the visualization of the monoamino oxidase A using harmol derivatives. Whereas two are for prosthetic group labeling using [F-18]fluoro-d(2)-methyl tosylate and 2-[F-18]fluoroethyl-tosylate, the other three precursors are for direct nucleophilic F-18-labeling. Additionally the corresponding reference compounds were synthesized. The syntheses of [F-18]fluoro-d(2)-methyl-harmol and 2-[F-18] fluoroethyl-harmol were carried out using harmol as starting material. For direct nucleophilic F-18-labeling of the tracers carrying oligoethyled spacers (PEG), a toluenesulfonyl leaving group was employed. The radiolabeling, purification and formulation for each tracer was optimized and evaluated in vitro and in vivo. Stability tests in human serum showed that all tracers were stable over the observation period of 60 min. mu PET studies using of the synthesized tracers revealed that the tracers carrying PEG spacers showed no sufficient brain uptake. Consequently, the F-18-fuoro alkylated tracers [F-18] fluoro-d2-methyl-harmol and 2-[F-18]fluoroethyl-harmol were further evaluated showing SUVs in the brain of 1.0 +/- 0.2 g/mL and 3.4 +/- 0.5 g/mL after 45 min, respectively. In blockade studies the selectivity and specificity of both tracers were demonstrated. However, for [F-18]fluoro-d(2)-methyl-harmol a rapid washout from the brain was also observed. In vitro binding assays revealed that 2-[F-18] fluoroethyl-harmol (IC50 = 0.54 +/- 0.06 nM) has a higher affinity than the F-18-fluoro-d(2)-methylated ligand (IC50 = 12.2 +/- 0.6 nM), making 2-[F-18] fluoroethyl-harmol superior to the other evaluated compounds and a promising tracer for PET imaging of the MAO A. (C) 2014 Elsevier Ltd. All rights reserved.