ethane-1,2-diyl-d4 bis(4-methylbenzenesulfonate) | 164936-35-0

• 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: ethane-1,2-diyl-d4 bis(4-methylbenzenesulfonate)
• 英文别名: [1,1,2,2-tetradeuterio-2-(p-tolylsulfonyloxy)ethyl] 4-methylbenzenesulfonate；[1,1,2,2-tetradeuterio-2-(4-methylphenyl)sulfonyloxyethyl] 4-methylbenzenesulfonate
• CAS: 164936-35-0
• 化学式: C₁₆H₁₈O₆S₂
• 分子量: 374.416
• InChiKey: LZIPBJBQQPZLOR-AREBVXNXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethane-1,2-diyl-d4 bis(4-methylbenzenesulfonate) 在 Rh/Al₂O₃ 氢气 、 potassium carbonate 作用下， 以 乙醇 、 乙腈 为溶剂， 40.0 ℃ 、4.14 MPa 条件下， 反应 260.0h， 生成
  参考文献：
  名称：

  Buchanan, G. W.; Moghimi, A.; Reynolds, V. M., Canadian Journal of Chemistry, 1995, vol. 73, # 4, p. 566 - 572

  摘要：

  DOI：
• 作为产物：
  描述：

  氘代乙二醇-d6 、 对甲苯磺酰氯 在 吡啶 作用下， 以76%的产率得到ethane-1,2-diyl-d4 bis(4-methylbenzenesulfonate)
  参考文献：
  名称：

  Synthesis and Evaluation of Two ¹⁸F-Labeled 6-Iodo-2-(4‘-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine Derivatives as Prospective Radioligands for β-Amyloid in Alzheimer's Disease

  摘要：

  This study evaluated F-18-labeled IMPY [6-iodo-2-(4'-N,N-dimethylamino)phenylimidazo[1,2-a]pyridine] derivatives as agents for imaging beta-amyloid plaque with positron emission tomography (PET). The precursor for radiolabeling and reference compounds was synthesized in up to five steps from commercially accessible starting materials. One of the two N-methyl groups of IMPY was substituted with either a 3-fluoropropyl (FPM-IMPY) or a 2-fluoroethyl (FEM-IMPY) group. FPM-IMPY and FEM-IMPY were found to have moderate affinity for Abeta-aggregates with K-i = 27 +/- 8 and 40 +/- 5 nM, respectively. A "one-pot" method for F-18-2-fluoroethylation and F-18-3-fluoropropylation of the precursor was developed. The overall decay-corrected radiochemical yields were 26-51%. In PET experiments with normal mouse, high uptake of activity was obtained in the brain after iv injection of each probe: 6.4% ID/g for [F-18]FEM-IMPY at 1.2 min, and 5.7% ID/g for [F-18]FPM-IMPY at 0.8 min. These values were similar to those of [I-123/I-123]IMPY (7.2% ID/g at 2 min). Polar and nonpolar radioactive metabolites were observed in both plasma and brain homogenates after injection of [F-18]FEM or [F-18]FPM-IMPY. In contrast to the single-exponential washout of [I-123/I-123]IMPY, the washouts of brain activity for the two fluorinated analogues were biphasic, with an initial rapid phase over 20 min and a subsequent much slower phase. Residual brain activity at 2 h, which may represent polar metabolites trapped in the brain, was 4.5% ID/g for [F-18] FEM-IMPY and 2.1% ID/g for [F-18]FPM-IMPY. Substantial skull uptake of [F-18]fluoride was also clearly observed. With a view to slow the metabolism of [F-18]FEM-IMPY, an analogue was prepared with deuteriums substituted for the four ethyl hydrogens. However, D-4-[F-18]FEM-IMPY showed the same brain uptake and clearance as the protio analogue. Metabolism of the [F-18]FEM-IMPY was appreciably slower in rhesus monkey than in mouse. Autoradiography of postmortem brain sections of human Alzheimer's disease patients with [F-18]FEM-IMPY showed high displaceable uptake in gray matter and low nonspecific binding in the white matter. This study demonstrates that the IMPY derivatives have favorable in vivo brain pharmacokinetics and a moderate affinity for imaging beta-amyloid plaques; however, further improvements are needed to reduce radioactive metabolites, increase binding affinity, and reduce lipophilicity.

  DOI：

  10.1021/jm030477w

文献信息

• [EN] RADIOLABELED COMPOUNDS AND THEIR USE AS RADIOTRACERS FOR QUANTITATIVE IMAGING OF PHOSPHODIESTERASE (PDE10A) IN MAMMALS<br/>[FR] COMPOSÉS RADIOMARQUÉS ET LEUR UTILISATION EN TANT QUE RADIOTRACEURS POUR L'IMAGERIE QUANTITATIVE DE LA PHOSPHODIESTÉRASE (PDE10A) CHEZ LES MAMMIFÈRES
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2013027845A1

  公开（公告）日：2013-02-28

  The present invention provides radiolabeled compounds useful as radiotracers for quantitative imaging of PDE10A in mammals. The compound of the present invention is represented by the formula (I): wherein each symbols are as defined in the specification.

  本发明提供了用作哺乳动物中PDE10A定量成像的放射标记化合物，该化合物由以下公式（I）表示：其中每个符号如规范中定义。
• Synthesis of³H,²H₄, and¹⁴C-MK 3814 (preladenant)
  作者：D. Hesk、S. Borges、R. Dumpit、S. Hendershot、D. Koharski、P. McNamara、S. Ren、S. Saluja、V. Truong、K. Voronin

  DOI：10.1002/jlcr.3490

  日期：2017.4

  MK 3814 is a potent and selective antagonist of the A2a receptor. A2a receptor antagonists have the potential for the treatment of Parkinson disease. Three distinct isotopically labelled forms of MK 3814 were synthesized. [3H]MK 3814 was prepared for a preliminary absorption, distribution, metabolism, and excretion data (ADME) evaluation of the compound and [14C]MK 3814 for more definitive ADME work, including an absorption, metabolism, and excretion study in man. In addition, [2H4]MK 3814 was prepared as an internal standard for a liquid chromatography mass spectrometry bioanalytical method. This paper discusses the synthesis of 3 isotopically labelled forms of MK 3814.

  MK 3814 是一种有效的选择性 A2a 受体拮抗剂。 A2a 受体拮抗剂具有治疗帕金森病的潜力。合成了三种不同同位素标记形式的 MK 3814。 [3H]MK 3814 用于化合物的初步吸收、分布、代谢和排泄数据 (ADME) 评估，[14C]MK 3814 用于更明确的 ADME 工作，包括人体吸收、代谢和排泄研究。此外，制备了[2H4]MK 3814作为液相色谱质谱生物分析方法的内标。本文讨论了 MK 3814 3 种同位素标记形式的合成。
• Improved in vivo PET imaging of the adenosine A2A receptor in the brain using [18F]FLUDA, a deuterated radiotracer with high metabolic stability
  作者：Thu Hang Lai、Magali Toussaint、Rodrigo Teodoro、Sladjana Dukić-Stefanović、Daniel Gündel、Friedrich-Alexander Ludwig、Barbara Wenzel、Susann Schröder、Bernhard Sattler、Rareş-Petru Moldovan、Björn H. Falkenburger、Osama Sabri、Winnie Deuther-Conrad、Peter Brust

  DOI：10.1007/s00259-020-05164-4

  日期：2021.8

  The adenosine A_2A receptor has emerged as a therapeutic target for multiple diseases, and thus the non-invasive imaging of the expression or occupancy of the A_2A receptor has potential to contribute to diagnosis and drug development. We aimed at the development of a metabolically stable A_2A receptor radiotracer and report herein the preclinical evaluation of [¹⁸F]FLUDA, a deuterated isotopologue of [¹⁸F]FESCH.

  [¹⁸F]FLUDA was synthesized by a two-step one-pot approach and evaluated in vitro by autoradiographic studies as well as in vivo by metabolism and dynamic PET/MRI studies in mice and piglets under baseline and blocking conditions. A single-dose toxicity study was performed in rats.

  [¹⁸F]FLUDA was obtained with a radiochemical yield of 19% and molar activities of 72–180 GBq/μmol. Autoradiography proved A_2A receptor–specific accumulation of [¹⁸F]FLUDA in the striatum of a mouse and pig brain. In vivo evaluation in mice revealed improved stability of [¹⁸F]FLUDA compared to that of [¹⁸F]FESCH, resulting in the absence of brain-penetrant radiometabolites. Furthermore, the radiometabolites detected in piglets are expected to have a low tendency for brain penetration. PET/MRI studies confirmed high specific binding of [¹⁸F]FLUDA towards striatal A_2A receptor with a maximum specific-to-non-specific binding ratio in mice of 8.3. The toxicity study revealed no adverse effects of FLUDA up to 30 μg/kg, ~ 4000-fold the dose applied in human PET studies using [¹⁸F]FLUDA.

  The new radiotracer [¹⁸F]FLUDA is suitable to detect the availability of the A_2A receptor in the brain with high target specificity. It is regarded ready for human application.

  摘要 目的：腺苷A2A受体已成为多种疾病的治疗靶点，因此非侵入性成像A2A受体的表达或占位有潜力为诊断和药物开发做出贡献。我们旨在开发一种代谢稳定的A2A受体放射性示踪剂，并在此处报告[18F]FLUDA的临床前评估，它是[18F]FESCH的氘同位素。 方法：[18F]FLUDA通过两步一锅法合成，并通过体外放射自显影研究以及小鼠和仔猪的代谢和动态PET / MRI研究在基线和阻断条件下进行体内评估。在大鼠中进行了单剂量毒性研究。 结果：[18F]FLUDA的放射化学收率为19％，摩尔活性为72-180 GBq /μmol。自显影证明了小鼠和猪脑中[18F]FLUDA在纹状体中的A2A受体特异性积累。小鼠体内评估显示[18F]FLUDA的稳定性优于[18F]FESCH，导致无脑可渗透放射性代谢物。此外，仔猪检测到的放射性代谢物预计具有较低的大脑穿透倾向。PET / MRI研究证实[18F]FLUDA对纹状体A2A受体具有高度特异性结合，小鼠的最大特异性结合比为8.3。毒性研究显示[18F]FLUDA在30 μg / kg（约为人类PET研究中应用的剂量的4000倍）时没有不良影响。 结论：新的放射性示踪剂[18F]FLUDA适用于检测大脑中A2A受体的可用性，具有高度的靶点特异性。它被认为已准备好应用于人体。
• Synthesis and Biological Evaluation of [18F]FECNT-d4 as a Novel PET Agent for Dopamine Transporter Imaging
  作者：Shanshan Cao、Jie Tang、Chunyi Liu、Yi Fang、Linyang Ji、Yingjiao Xu、Zhengping Chen

  DOI：10.1007/s11307-021-01603-2

  日期：2021.10

  Purpose The dopamine transporter (DAT) is a marker of the occurrence and development of Parkinson’s disease (PD) and other diseases with nigrostriatal degeneration. 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl)nortropane ([18F]FECNT), an 18F-labelled tropane derivative, was reported to be a useful positron-emitting probe for DAT. However, the rapid formation of brain-penetrating radioactive

  目的 多巴胺转运蛋白（DAT）是帕金森病（PD）和其他伴有黑质纹状体变性的疾病发生和发展的标志物。2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-[ 18 F]-fluoroethyl)nortropane ([ 18 F]FECNT)，一种18 F 标记的托烷衍生物，据报道是一种有用的正电子发射探测 DAT。然而，在使用 [ 18 F]FECNT的 PET 研究中，快速形成可穿透大脑的放射性代谢物阻碍了 DAT 的正确定量。氘取代的类似物在减少代谢物方面表现出更好的体内稳定性。本研究旨在合成一种氘取代的 DAT 放射性示踪剂，[ 18 F]FECNT- d4、对其作为体内DAT示踪剂的性质进行初步考察。 程序 通过一步放射性标记反应获得配体[ 18 F]FECNT- d 4 。亲脂性通过摇瓶法测量。[ 18 F]FECNT- d 4的结合特性通过大鼠体外结合测定、生物分布和
• Automated radiosynthesis of the adenosine A _2A receptor‐targeting radiotracer [ ¹⁸ F]FLUDA
  作者：Thu Hang Lai、Barbara Wenzel、Rareş‐Petru Moldovan、Peter Brust、Klaus Kopka、Rodrigo Teodoro

  DOI：10.1002/jlcr.3970

  日期：2022.5.30

  [18 F]FLUDA is a selective radiotracer for in vivo imaging of the adenosine A2A receptor (A2A R) by positron emission tomography (PET). Promising preclinical results obtained by neuroimaging of mice and piglets suggest the translation of [18 F]FLUDA to human PET studies. Thus, we report herein a remotely controlled automated radiosynthesis of [18 F]FLUDA using a GE TRACERlab FX2 N radiosynthesizer

  [18 F]FLUDA 是一种选择性放射性示踪剂，用于通过正电子发射断层扫描 (PET) 对腺苷 A2A 受体 (A2A R) 进行体内成像。通过小鼠和仔猪的神经影像学获得的有希望的临床前结果表明 [18 F] FLUDA 可用于人类 PET 研究。因此，我们在此报告了使用 GE TRACERlab FX2 N 放射合成仪对 [18 F]FLUDA 进行远程控制的自动放射合成。该放射性示踪剂采用一锅二步放射性氟化法获得，放射化学收率9±1%，放射化学纯度≥99%，合成结束时摩尔活度在69-333 GBq/μmol范围内。在大约的总合成时间内。95 分钟（n = 16）。总而言之，我们成功地建立了一种可靠且可重复的 [18 F] FLUDA 自动化生产程序。