2-[18F]fluoroethyl triflate | 124840-53-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: 2-[18F]fluoroethyl triflate
• 英文别名: [¹⁸F]fluoroethyl triflate；2-(18F)fluoranylethyl trifluoromethanesulfonate
• CAS: 124840-53-5
• 化学式: C₃H₄F₄O₃S
• 分子量: 195.124
• InChiKey: BATWFDBKHDIXSM-NUTRPMROSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  51.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-[18F]fluoroethyl triflate 、 Hydroxy-diphenyl-acetic acid (R)-piperidin-3-yl ester 以 乙腈 为溶剂， 反应 0.03h， 生成 (R)-hydroxydiphenylacetic acid N-(2-[18]fluoroethyl)piperidin-3-yl ester
  参考文献：
  名称：

  Synthesis, ¹⁸F-Labeling, and Biological Evaluation of Piperidyl and Pyrrolidyl Benzilates as in Vivo Ligands for Muscarinic Acetylcholine Receptors

  摘要：

  A series of 31 compounds based on the piperidyl or pyrrolidyl benzilate scaffold were prepared from methyl benzilate and 4-piperidinol, (R)-(+)-3-piperidinol, or (R)-(+)-3-pyrrolidinol. Amine substituents included alkyl and aralkyl groups. In vitro K-i values ranged from 0.05 nM to > 100 nM. (R)-N-( 2-Fluoroethyl)-3-piperidyl benzilate (3-FEPB, 22, K-i = 12.1 nM) and N-(2-fluoroethyl)-4-piperidyl benzilate (4-FEPB, 8, K-i = 1.83 nM) were selected for radiolabeling with fluorine-18. Using alkylation with 2-[F-18]fluoroethyl triflate, 3-[F-18]FEPB (42) and 4-[F-18]-FEPB (43) were produced in 7-9% radiochemical yield and >97% radiochemical purity. For in vivo studies, retention was moderate in mouse brain for 42; however, blocking with scopolamine showed that uptake was not muscarinic cholinergic receptor-mediated. Conversely, 43 exhibited high, receptor-mediated retention in mouse brain, with significant; clearance after 1 h. These results suggest that 43 could have applications as an in vivo probe for measuring endogenous acetylcholine levels.

  DOI：

  10.1021/jm000305o
• 作为产物：
  描述：

  甲磺酸,三氟-,1,2-乙二基酯 在 potassium [¹⁸F]fluoride 、 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 乙腈 为溶剂， 反应 2.0h， 生成 2-[18F]fluoroethyl triflate
  参考文献：
  名称：

  两种正电子标记的一氧化氮合酶抑制剂S- [11C]甲基异硫脲和S-（2- [18F]氟乙基）异硫脲的合成和评价，作为潜在的正电子发射断层显像示踪剂。

  摘要：

  为了开发一种示踪剂以利用正电子发射断层扫描技术在体内探测诱导型一氧化氮合酶（iNOS）的示踪剂，我们合成并评估了两种发射正电子的iNOS选择性抑制剂：S- [11C]甲基异硫脲（1b）和S-（ 2- [18F]氟乙基）-异硫脲（3b）。在进行氟18标记之前，制备了非放射性氟衍生物S-（2-氟乙基）异硫脲（3a），并确定其对iNOS的选择性比内皮NOS（eNOS）高9倍。通过标记的前体（11CH3I或18FCH2CH2OTf）与硫脲的S-烷基化反应，可以实现高放射化学纯度和高比活度的两种化合物的放射化学合成。体外模型，J774巨噬细胞系，用于评估在细胞水平上对iNOS诱导反应的放射性标记iNOS抑制剂的摄取。观察到在受刺激的iNOS水平上，这两种标记化合物的细胞摄取增加，并且在受控的体外条件下被阻断。报告了这两种化合物的亲脂性（log P o / w），稳定性和组织生物分布数据。血清稳定性研

  DOI：

  10.1021/jm960481q

文献信息

• Synthesis, radiolabeling and evaluation of novel amine guanidine derivatives as potential positron emission tomography tracers for the ion channel of the N-methyl-d-aspartate receptor
  作者：Pieter J. Klein、Marion Chomet、Athanasios Metaxas、Johannes A.M. Christiaans、Esther Kooijman、Robert C. Schuit、Adriaan A. Lammertsma、Bart N.M. van Berckel、Albert D. Windhorst

  DOI：10.1016/j.ejmech.2016.04.022

  日期：2016.8

  N-Methyl-d-Aspartate receptor (NMDAR) is involved in many neurological and psychiatric disorders including Alzheimer's disease and schizophrenia. The aim of this study was to develop a positron emission tomography (PET) ligand to assess the bio-availability of the NMDAR ion channel in vivo. A series of tri-N-substituted diarylguanidines was synthesized and their in vitro binding affinities for the NMDAR ion channel

  的Ñ -甲基- d -天冬氨酸受体（NMDAR）参与许多神经障碍和精神障碍，包括阿尔茨海默氏病和精神分裂症。这项研究的目的是开发一种正电子发射断层扫描（PET）配体，以评估NMDAR离子通道在体内的生物利用度。合成了一系列的三-N-取代的二芳基胍，并在大鼠前脑膜级分中评估了它们对NMDAR离子通道的体外结合亲和力。化合物21，23和26与任一碳-11或氟-18并放射性标记体外在Wistar大鼠中进行了生物分布和代谢物研究。生物分布研究表明，尤其是在额叶前额皮层中摄取较高，而在小脑中摄取最低。但是，用MK-801进行预处理不会降低对放射性标记配体的吸收。另外，所有三个配体均显示出快速的新陈代谢。
• [EN] RADIOLABELED MONOACYLGLYCEROL LIPASE OCCUPANCY PROBE<br/>[FR] SONDE DE PRÉSENCE DE MONOACYLGLYCÉROL LIPASE RADIOMARQUÉE
  申请人：ABIDE THERAPEUTICS INC

  公开号：WO2017143283A1

  公开（公告）日：2017-08-24

  Provided herein are monoacylglycerol lipase (MGLL) occupancy probes comprising a MGLL inhibitor containing a positron emission tomography (PET) tracer radionuclide. Also provided are methods of assessing MGLL enzyme occupancy of a MGLL inhibitor using the radiolabeled occupancy probes described herein.

  本文提供了一种包含单酰基甘油酶（MGLL）占位探针的MGLL抑制剂，其中包含正电子发射断层扫描（PET）示踪剂放射性核素。还提供了利用本文描述的放射性标记占位探针评估MGLL抑制剂对MGLL酶占位的方法。
• Synthesis and Evaluation of New Fluorine-18 Labeled Verapamil Analogs To Investigate the Function of P-Glycoprotein in the Blood–Brain Barrier
  作者：Renske M. Raaphorst、Gert Luurtsema、Robert C. Schuit、Esther J. M. Kooijman、Philip H. Elsinga、Adriaan A. Lammertsma、Albert D. Windhorst

  DOI：10.1021/acschemneuro.7b00086

  日期：2017.9.20

  blood–brain barrier. (R)-[11C]Verapamil is widely used as a PET tracer to investigate its function in patients with epilepsy, Alzheimer’s disease, and other neurodegenerative diseases. Currently it is not possible to use this successful tracer in clinics without a cyclotron, because of the short half-life of carbon-11. We developed two new fluorine-18 labeled (R)-verapamil analogs, with the benefit of a longer

  P-糖蛋白是位于血脑屏障中的外排转运蛋白。（R）-[ 11 C]维拉帕米被广泛用作PET示踪剂，以研究其在癫痫，阿尔茨海默氏病和其他神经退行性疾病患者中的功能。由于碳11的半衰期短，目前无法在没有回旋加速器的诊所中使用这种成功的示踪剂。我们开发了两个新的氟18标记的（R）-维拉帕米类似物，具有更长的半衰期。（R）-N- [ 18 F]氟乙基维拉帕米（[ 18 F] 1）和（R）-O- [ 18已经描述了F]氟乙基去甲维拉帕米（[ 18 F] 2）。[ 18 F] 1是在（R）-去甲拉帕米与从溴乙基甲苯磺酸盐和三硫酸银柱中获得的挥发性[ 18 F]氟乙基三氟甲磺酸盐的反应中获得的，其放射化学产率为2.7％±1.2％。[ 18 F] 2通过前体13的直接氟化进行了放射性标记，需要用TFA进行最终的Boc脱保护，其放射化学产率为17.2％±9.9％。两种示踪剂，[ 18 F] 1和[ 18 F]
• Multiple Applications of a Novel Biarsenical Imaging Probe in Fluorescence and PET Imaging of Melanoma
  作者：Mikhail Kondrashov、Samuel P. S. Svensson、Peter Ström、Andreas Westermark、Hanna Jacobson-Ingemyr、Akihiro Takano、Lenke Tari、Miklós Tóth、Minying Cai、Victor J. Hruby、Magnus Schou

  DOI：10.1021/acs.bioconjchem.0c00671

  日期：2021.3.17

  biarsenical peptide labeling probe was synthesized and labeled with the radioactive isotopes 11C and 18F. The utility of this probe was demonstrated by installing each of these isotopes into a melanocortin 1 receptor (MC1R) binding peptide, which targets melanoma tumors. Its applicability was further showcased by subsequent in vitro imaging in cells as well as in vivo imaging in melanoma xenograft mice

  合成了一种新的荧光双砷肽标记探针，并用放射性同位素11 C 和18 F 进行标记。通过将这些同位素中的每一种安装到黑色素皮质素 1 受体 (MC1R) 结合肽中，证明了该探针的效用，该肽靶向黑色素瘤肿瘤。随后通过荧光和正电子发射断层扫描在细胞中进行体外成像以及在黑色素瘤异种移植小鼠体内成像，进一步展示了其适用性。
• How to increase the reactivity of [18F]fluoroethyl bromide: [18F]fluoroethylation of amine, phenol and amide functional groups with [18F]FEtBr, [18F]FEtBr/NaI and [18F]FEtOTf
  作者：Ming-Rong Zhang、Kenji Furutsuka、Yuichiro Yoshida、Kazutoshi Suzuki

  DOI：10.1002/jlcr.703

  日期：2003.5

  [18F]Fluoroethyl bromide ([18F]FEtBr) is a useful synthetic precursor to synthesize 18F-labeled compounds. However, the lower reactivity of [18F]FEtBr with amine, phenol and amide functional groups than that of [11C]CH3I partly limits its wide application in the synthesis of [18F]fluoroethylated compounds. The aim of this study was to increase the reactivity of [18F]FEtBr with various nucleophilic substrates for PET tracers containing amine, phenol and amide moieties. The present strategies included (1) adding NaI into the reaction mixture of [18F]FEtBr and substrate, where [18F]FEtI is reversibly formed and becomes more reactive; (2) converting [18F]FEtBr into much more reactive [18F]FEtOTf, similar to conversion of [11C]CH3I into [11C]CH3OTf. By these efforts, the [18F]fluoroethylation efficiency of various substrates containing amine, phenol and amide groups with [18F]FEtBr/NaI and [18F]FEtOTf was significantly improved, compared with the corresponding reaction efficiency with [18F]FEtBr. Copyright © 2003 John Wiley & Sons, Ltd.

  [18F]氟乙基溴 ([18F]FEtBr) 是合成 18F 标记化合物的有用合成前体。然而，[18F]FEtBr与胺、酚和酰胺官能团的反应活性低于[11C]CH3I，部分限制了其在[18F]氟乙基化化合物合成中的广泛应用。本研究的目的是提高 [18F]FEtBr 与各种亲核底物的反应性，用于含有胺、苯酚和酰胺部分的 PET 示踪剂。目前的策略包括（1）将NaI添加到[18F]FEtBr和底物的反应混合物中，其中[18F]FEtI可逆地形成并变得更具反应性； (2) 将[ 18F]FEtBr 转化为更具反应性的[ 18F]FEtOTf ，类似于将[ 11C]CH3I 转化为[ 11C]CH3OTf 。通过这些努力，与[18F]FEtBr的相应反应效率相比，[18F]FEtBr/NaI和[18F]FEtOTf对各种含有胺、酚和酰胺基团的底物的[18F]氟乙基化效率显着提高。版权所有 © 2003 约翰·威利父子有限公司