fluoromethyl-d2 4-methylbenzenesulfonate | 1180485-67-9

• 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: fluoromethyl-d2 4-methylbenzenesulfonate
• 英文别名: [Dideuterio(fluoro)methyl] 4-methylbenzenesulfonate
• CAS: 1180485-67-9
• 化学式: C₈H₉FO₃S
• 分子量: 206.206
• InChiKey: RFCGZPLGJZELOK-NCYHJHSESA-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：

  fluoromethyl-d2 4-methylbenzenesulfonate 、 拉罗替尼 在 potassium tert-butylate 、 四丁基氟化铵 作用下， 以 乙腈 为溶剂， 反应 21.17h， 以29.2%的产率得到
  参考文献：
  名称：

  一种烷氧基取代的拉曲替尼化合物及其制备方法和用途

  摘要：

  本发明涉及一种烷氧基取代的拉曲替尼化合物及其制备方法和用途，包括放射性原子或非放射性原子标记的拉曲替尼，其中放射性原子包括11C、3H、18F，非放射性原子包括12C、2H、19F。与现有技术相比，本发明烷氧基拉曲替尼类似物是一种新型的TRK PET探针，具有TRK特异性，借助于PET(Positron emission tomography)非浸入性显像技术，具有在活体内分子水平上实现药物分子生理生化功能、药理学过程的可视化和定量化评估。

  公开号：

  CN112174967A
• 作为产物：
  描述：

  silver(I) 4-methylbenzenesulfonate 在 六甘醇 、 cesium fluoride 作用下， 以 乙腈 为溶剂， 反应 3.5h， 生成 fluoromethyl-d2 4-methylbenzenesulfonate
  参考文献：
  名称：

  Re-exploring the N-phenylpicolinamide derivatives to develop mGlu4 ligands with improved affinity and in vitro microsomal stability

  摘要：

  In recent years, mGlu(4) has received great attention and research effort because of the potential benefits of mGlu(4) activation in treating numerous brain disorders, such as Parkinson's disease (PD). Many positive allosteric modulators of mGlu(4) have been developed. To better understand the role of mGlu(4) in healthy and disease conditions, we are interested in developing an mGlu(4) selective radioligand for in vivo studies. Thus, we had synthesized and studied [C-11]2 as a PET tracer for mGlu(4), which demonstrated some promising features as a PET radioligand as well as the limitation need to be improved. In order to develop an mGlu(4) ligand with enhanced affinity and improved metabolic stability, we have modified, synthesized and evaluated a series of new N-phenylpicolinamide derivatives. The SAR study has discovered a number of compounds with low nM affinity to mGlu(4). The dideuteriumfluoromethoxy modified compound 24 is identified as a very promising mGlu(4) ligand, which has demonstrated enhanced affinity, improved in vitro microsomal stability, good selectivity and good permeability. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.031
• 作为试剂：
  描述：

  N-(2-hydroxybenzyl)-N-(4-phenoxypyridin-3-yl)acetamide 在 fluoromethyl-d2 4-methylbenzenesulfonate 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 24.0h， 以28%的产率得到
  参考文献：
  名称：

  [ 18 F]氟甲基-PBR28及其氘代类似物在神经炎症大鼠模型中的临床前比较研究

  摘要：

  我们设计并合成了氘取代的[ 18 F]氟甲基-PBR28（[ 18 F] 1 - d 2）作为一种新型的转运蛋白18 kDa（TSPO）靶向放射性配体，具有增强的体内稳定性。从体外结合亲和力，亲脂性和体内活性方面研究了[ 18 F]氟甲基-PBR28（[ 18 F] 1）与它的氘代类似物（[ 18 F] 1 - d 2）的比较研究。稳定。此外，通过在相同的LPS诱发的神经炎症大鼠模型中比较PET成像数据，确定了两种放射性配体的准确性。两种芳氧基苯胺类似物均表现出相似的亲脂性和对TSPO的体外亲和力。然而，在离体生物分布研究中，[ 18 F] 1 - d 2提供的股骨摄取明显低于[ 18 F] 1（注射后2 h为1.5±1.2 vs. 4.1±1.7％ID / g）。[ 18楼] 1 - d 2 在LPS诱发的急性神经炎症大鼠模型中，脂蛋白也选择性地聚集在炎性病变中，具有特异性结合的放射性配

  DOI：

  10.1016/j.bmcl.2018.07.011

文献信息

• HPLC-free <i>in situ</i>¹⁸F-fluoromethylation of bioactive molecules by azidation and MTBD scavenging
  作者：Yingqing Lu、Ji Young Choi、Sang Eun Kim、Byung Chul Lee

  DOI：10.1039/c9cc04901k

  日期：——

  Sequential usage of azide and MTBD, which generates pure [¹⁸F]fluoromethyl tosylate and scavenges unreacted desmethyl precursors, provided an efficient HPLC-free strategy for the radio-synthesis of ¹⁸F-fluoromethylated compounds.

  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。
• [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。
• Development of 2-(2-(3-(4-([¹⁸F]Fluoromethoxy-<i>d</i>₂)phenyl)-7-methyl-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione for Positron-Emission-Tomography Imaging of Phosphodiesterase 10A in the Brain
  作者：Wakana Mori、Tomoteru Yamasaki、Masayuki Fujinaga、Masanao Ogawa、Yiding Zhang、Akiko Hatori、Lin Xie、Katsushi Kumata、Hidekatsu Wakizaka、Yusuke Kurihara、Takayuki Ohkubo、Nobuki Nengaki、Ming-Rong Zhang

  DOI：10.1021/acs.jmedchem.8b01366

  日期：2019.1.24

  disorders. 2-(2-(3-(4-([18F]Fluoroethoxy)phenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)ethyl)-4-isopropoxyisoindoline-1,3-dione ([18F]MNI-659, [18F]5) is a useful positron-emission-tomography (PET) ligand for imaging of PDE10A in the human brain. However, the radiolabeled metabolite of [18F]5 can accumulate in the brain. In this study, using [18F]5 as a lead compound, we designed four new 18F-labeled ligands

  磷酸二酯酶10A（PDE10A）是新近确定的中枢神经系统疾病的治疗靶标。2-（2-（3-（4-（[ 18 F]氟乙氧基）苯基）-4-氧代-3,4-二氢喹唑啉-2-基）乙基）-4-异丙氧基异吲哚啉-1,3-二酮（[ 18 F] MNI-659，[ 18 F] 5）是用于在人脑中对PDE10A成像的有用的正电子发射断层扫描（PET）配体。但是，[ 18 F] 5的放射性标记代谢物会在大脑中积聚。在这项研究中，我们以[ 18 F] 5为先导化合物，设计了四个新的18 F标记的配体（[ 18 F] 6 – 9）找到比[ 18 F] 5更合适的一种。其中，2-（2-（3-（4-（[[ 18 F]氟甲氧基-d 2）苯基）-4-氧代-3,4-二氢喹唑啉-2-基）乙基）-4-异丙氧基异吲哚啉-1， 3-二酮（[ 18 F] 9）对PDE10A表现出高的体外结合亲和力（K i = 2.9 nM）和合适的亲脂性（log
• 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
• Synthesis, Ex Vivo Evaluation, and Radiolabeling of Potent 1,5-Diphenylpyrrolidin-2-one Cannabinoid Subtype-1 Receptor Ligands as Candidates for In Vivo Imaging
  作者：Sean R. Donohue、Joseph H. Krushinski、Victor W. Pike、Eyassu Chernet、Lee Phebus、Amy K. Chesterfield、Christian C. Felder、Christer Halldin、John M. Schaus

  DOI：10.1021/jm800416m

  日期：2008.9.25

  We have reported that [methyl-C-11] (3R,5R)-5-(3-methoxyphenyl)-3-[(R)-1-phenylethylamino]-1-(4-trifluoromethylphenyl)pyrrolidin-2-one ([C-11]8, [C-11]MePPEP) binds with high selectivity to cannabinoid type-l (CB1) receptors in monkey brain in vivo. We now describe the synthesis of 8 and four analogues, namely, the 4-fluorophenyl (16, FMePPEP), 3-fluoromethoxy (20, FMPEP), 3-fluoromethoxy-d(2) (21, FMPEP-d(2)), and 3-fluoroethoxy analogues (22, FEPEP), and report their activity in an ex vivo model designed to identify compounds suitable for use as positron emission tomography (PET) ligands. These ligands exhibited high, selective potency at CB I receptors in vitro (K-b < 1 nM). Each ligand (30 mu g/kg, iv) was injected into rats under baseline and pretreatment conditions (3, rimonabant, 10 mg/kg, iv) and quantified at later times in frontal cortex ex vivo with liquid chromatography-mass spectrometry (LC-MS) detection. Maximal ligand uptakes were high (22.6-48.0 ng/g). Under pretreatment, maximal brain uptakes were greatly reduced (6.5 - 17.3 ng/g). Since each ligand readily entered brain and bound with high selectivity to CB 1 receptors, we then established and here describe methods for producing [C-11]8, [C-11] 16, and [[F-18]20-22 in adequate activities for evaluation as candidate PET radioligands in vivo.