[¹⁸F]fluoro-d₂-methyl tosylate | 1454889-24-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [¹⁸F]fluoro-d₂-methyl tosylate
• 英文别名: [Dideuterio(fluoranyl)methyl] 4-methylbenzenesulfonate；[dideuterio(fluoranyl)methyl] 4-methylbenzenesulfonate
• CAS: 1454889-24-7
• 化学式: C₈H₉FO₃S
• 分子量: 205.208
• InChiKey: RFCGZPLGJZELOK-HZYDYNLBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  51.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  哈尔酚 、 [¹⁸F]fluoro-d₂-methyl tosylate 在 sodium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 0.33h， 生成 [¹⁸F]fluoro-d₂-methylharmol
  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
• 作为产物：
  描述：

  silver(I) 4-methylbenzenesulfonate 在 K_2.2.2/K¹⁸F 作用下， 以 水 、 乙腈 为溶剂， 反应 16.25h， 生成 [¹⁸F]fluoro-d₂-methyl tosylate
  参考文献：
  名称：

  HPLC-free in situ¹⁸F-fluoromethylation of bioactive molecules by azidation and MTBD scavenging

  摘要：

  使用叠氮和MTBD的顺序使用，生成纯[18F]氟甲基对甲苯磺酰基，并清除未反应的去甲基前体，为18F-氟甲基化合物的无HPLC合成提供了高效策略。

  DOI：

  10.1039/c9cc04901k

文献信息

• [EN] MODULATORS OF METABOTROPIC GLUTAMATE RECEPTOR 4<br/>[FR] MODULATEURS DU RÉCEPTEUR DU GLUTAMATE MÉTABOTROPIQUE 4
  申请人：MASSACHUSETTS GEN HOSPITAL

  公开号：WO2020146515A1

  公开（公告）日：2020-07-16

  The present application provides picolinamide compounds that can be used as allosteric positron emission tomography ("PET") imaging probes. Methods of using these compounds for treating a neurodegenerative disease are also provided.

  本申请提供了可以用作变构位置发射断层扫描（PET）成像探针的吡啶甲酰胺化合物。同时还提供了利用这些化合物治疗神经退行性疾病的方法。
• Synthesis and Characterization of Fluorine-18-Labeled <i>N</i>-(4-Chloro-3-((fluoromethyl-<i>d</i>₂)thio)phenyl)picolinamide for Imaging of mGluR4 in Brain
  作者：Junfeng Wang、Xiying Qu、Timothy M. Shoup、Gengyang Yuan、Sepideh Afshar、Chuzhi Pan、Aijun Zhu、Ji-Kyung Choi、Hye Jin Kang、Pekka Poutiainen、Georges El Fakhri、Zhaoda Zhang、Anna-Liisa Brownell

  DOI：10.1021/acs.jmedchem.0c00201

  日期：2020.3.26

  characterized [18F]-N-(4-chloro-3-((fluoromethyl-d2)thio)phenyl)-picolinamide ([18F]15) as a potential ligand for the positron emission tomography (PET) imaging of mGluR4 in the brain. Radioligand [18F]15 displays central nervous system drug-like properties, including mGluR4 affinity, potent mGluR4 PAM activity, and selectivity against other mGluRs, as well as sufficient metabolic stability. Radiosynthesis was

  我们合成并表征了[18F]-N-(4-氯-3-((氟甲基-d2)硫代)苯基)-吡啶甲酰胺([18F]15)作为正电子发射断层扫描(PET)成像的潜在配体大脑中的 mGluR4。放射性配体 [18F]15 显示出中枢神经系统药物样特性，包括 mGluR4 亲和力、有效的 mGluR4 PAM 活性、针对其他 mGluR 的选择性以及足够的代谢稳定性。放射合成分两步进行。 [18F]15 的放射化学产率为 11.6 ± 2.9%（n = 7，衰减校正），纯度为 99%，摩尔活度为 84.1 ± 11.8 GBq/μmol。离体生物分布研究表明 [18F]15 在所有研究组织中可逆结合，包括脑、肝、心、肺和肾。雄性 Sprague Dawley 大鼠的 PET 成像研究表明，[18F]15 在已知表达 mGluR4 的大脑区域积聚。用未标记的 mGluR4 PAM 化合物 13（甲硫基类似物）和
• Identification and<i>in vivo</i>evaluation of a fluorine-18 rolipram analogue, [¹⁸F]MNI-617, as a radioligand for PDE4 imaging in mammalian brain
  作者：David Thomae、Thomas J. Morley、Hsiaoju S. Lee、Olivier Barret、Cristian Constantinescu、Caroline Papin、Ronald M. Baldwin、Gilles D. Tamagnan、David Alagille

  DOI：10.1002/jlcr.3389

  日期：2016.5.15

  R-(-)-rolipram. Herein we describe a small series of rolipram analogs that contain fluoro- or iodo-substituents that could be used as fluorine-18 PET or iodine-123 SPECT PDE4 radiotracers. This series was evaluated with an in vitro binding assay and a 4-(fluoromethyl) derivative of rolipram, MNI-617, was identified, with a five-fold increase in affinity for PDE4 (Kd = 0.26 nM) over R-(-)-rolipram (Kd = 1.6 nM)

  磷酸二酯酶 (PDE) 4 是中枢神经系统 (CNS) 中最普遍的 PDE，可催化细胞内 cAMP（二级信使）的水解。通过治疗性抑制 PDE4，可以稳定细胞内 cAMP 水平，并且可以改善精神和神经退行性疾病的症状，包括抑郁症、记忆力减退和帕金森氏病。靶向 PDE4 的放射性示踪剂可用于研究 PDE4 密度和功能，并以非侵入性方式在体内评估新的 PDE4 疗法，正如使用碳 11 标记的 PDE4 抑制剂 R-(-)-咯利普兰所显示的那样。在此，我们描述了一系列含有氟或碘取代基的咯利普兰类似物，可用作氟 18 PET 或碘 123 SPECT PDE4 放射性示踪剂。该系列通过体外结合测定进行评估，并鉴定出咯利普兰的 4-（氟甲基）衍生物 MNI-617，其对 PDE4 的亲和力（Kd = 0.26 nM）比 R-(-) 增加了 5 倍-咯利普兰 (Kd = 1.6 nM)。氘类似物 d2 -[(18)
• Automated synthesis and purification of [¹⁸F]fluoro-[<i>di-deutero</i>]methyl tosylate
  作者：Friederike Beyerlein、Markus Piel、Sabine Höhnemann、Frank Rösch

  DOI：10.1002/jlcr.3043

  日期：2013.6.15

  Automated synthetic procedures of [18F]fluoro-[di-deutero]methyl tosylate on a GE TRACERlab FX F-N module and a non-commercial synthesis module have been developed. The syntheses included azeotropic drying of the [18F]fluoride, nucleophilic 18F-fluorination of bis(tosyloxy)-[di-deutero]methane, HPLC purification and subsequent formulation of the synthesized [18F]fluoro-[di-deutero]methyl tosylate (d2-[18F]FMT) in organic solvents. Automation shortened the total synthesis time to 50 min, resulting in an average radiochemical yield of about 50% and high radiochemical purity (>98%). The possible application of this procedure to commercially available synthesis modules might be of significance for the production of deuterated 18F-fluoromethylated imaging probes in the future. Copyright © 2013 John Wiley & Sons, Ltd.

  在 GE TRACERlab FX F-N 模块和非商业合成模块上开发了[18F]氟-[二-deutero]甲基对甲苯磺酸盐的自动合成程序。合成过程包括[18F]氟化物的共沸干燥、双（对甲苯磺酰氧基）-[二-deutero]甲烷的亲核 18F 氟化、HPLC 纯化以及随后在有机溶剂中配制合成的[18F]氟-[二-deutero]甲基对甲苯磺酸盐（d2-[18F]FMT）。自动化将总合成时间缩短至 50 分钟，平均放射化学收率约为 50%，放射化学纯度高（>98%）。将这一程序应用于市售的合成模块可能对未来生产氚代 18F 氟甲基化成像探针具有重要意义。Copyright © 2013 John Wiley & Sons, Ltd. All Rights Reserved.
• Detailed radiosynthesis of [ ¹⁸ F]mG4P027 as a positron emission tomography radiotracer for mGluR4
  作者：Junfeng Wang、Sung‐Hyun Moon、Michael B. Cleary、Timothy M. Shoup、Georges El Fakhri、Zhaoda Zhang、Anna‐Liisa Brownell

  DOI：10.1002/jlcr.4011

  日期：2023.2

  We report here the detailed radiosynthesis of [18F]mG4P027, a metabotropic glutamate receptor 4 (mGluR4) PET radiotracer, which showed superior properties to the currently reported mGluR4 radiotracers. The radiosynthesis in the automated system has been challenging, therefore we disclose here the major limiting factors for the synthesis via step-by-step examination. And we hope this thorough study

  我们在此报告了 [ 18 F] mG4P027的详细放射合成，这是一种代谢型谷氨酸受体 4 (mGluR4) PET 放射性示踪剂，其显示出优于目前报道的 mGluR4 放射性示踪剂的特性。自动化系统中的放射合成一直具有挑战性，因此我们在此通过逐步检查公开了合成的主要限制因素。我们希望这项彻底的研究将有助于其未来的自动化供人类使用。