1H-咪唑-1-丙醇 | 150196-34-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1H-咪唑-1-丙醇
• 中文别名: 1-(2'-硝基-1'-咪唑基)-2-O-吡喃-3-O甲苯磺酰-丙二醇
• 英文名称: NITTP
• 英文别名: 3-(2-nitro-1H-imidazol-1-yl)-2-((tetrahydro-2H-pyran-2-yl)oxy)propyl 4-methylbenzenesulfonate；1-(2'-nitro-1'-imidazolyl)-2-O-tetrahydropyranyl-3-O-toluenesulfonyl propanediol；[3-(2-nitroimidazol-1-yl)-2-(oxan-2-yloxy)propyl] 4-methylbenzenesulfonate
• CAS: 150196-34-2
• 化学式: C₁₈H₂₃N₃O₇S
• 分子量: 425.463
• InChiKey: ADKHTOXGXAAZSE-UHFFFAOYSA-N

物化性质

• 熔点：
  105-107 °C
• 沸点：
  659.1±65.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  134
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1H-咪唑-1-丙醇 在 溶剂黄146 、 cesium fluoride 作用下， 以 四氢呋喃 、 2-甲基-2-丁醇 、 水 为溶剂， 反应 7.0h， 生成 氟甲氧甲基硝基咪唑乙醇
  参考文献：
  名称：

  Preliminary research on 1-(4-bromo-2-nitroimidazol-1-yl)-3-[ 18 F]fluoropropan-2-ol as a novel brain hypoxia PET tracer in a rodent model of stroke

  摘要：

  The synthesis of the new radiotracer precursor 4-Br-NITTP and the radiolabeling of the new tracer 1-(4-bromo-2-nitroimidazol-1-yl)-3-[F-18]fluoropropan-2-ol (4-Br-[F-18]FMISO) is reported. The cyclic voltammetry behaviour, neuronal cell toxicity, transport through the brain endothelial cell monolayer, in vivo PET imaging and preliminary calculations of the tracer uptake for a rodent model of stroke were studied for the new compound and the results were compared to those obtained with [F-18]FMISO, the current gold standard PET hypoxia tracer. The new PET brain hypoxia tracer is more easily reduced, has higher ClogP than [F-18]FMISO and it diffuses more rapidly through brain endothelial cells. The new compound is non-toxic to neuronal cells and it allows the in vivo mapping of stroke in mice with higher sensitivity. 4-Br-[F-18]FMISO is a good candidate for further development in ischemic stroke. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.06.023
• 作为产物：
  描述：

  2-((1,3-dibromopropan-2-yl)oxy)tetrahydro-2H-pyran 在 吡啶 、 氨 、 四丁基碘化铵 、 potassium carbonate 、 caesium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 1H-咪唑-1-丙醇
  参考文献：
  名称：

  [18F]-氟咪唑标记前体的新合成

  摘要：

  [18F]-氟米尼唑是最广泛用于肿瘤缺氧成像的放射性药物。[18F]-氟咪唑的前体是从 1,3-二溴-2-丙醇通过 5 个步骤从可用材料和简单的纯化步骤制备的。该合成的总产率为18%。版权所有 © 2005 John Wiley & Sons, Ltd.

  DOI：

  10.1002/jlcr.1001

文献信息

• A New Class of S_N2 Reactions Catalyzed by Protic Solvents:  Facile Fluorination for Isotopic Labeling of Diagnostic Molecules
  作者：Dong Wook Kim、Doo-Sik Ahn、Young-Ho Oh、Sungyul Lee、Hee Seup Kil、Seung Jun Oh、Sang Ju Lee、Jae Seung Kim、Jin Sook Ryu、Dae Hyuk Moon、Dae Yoon Chi

  DOI：10.1021/ja0646895

  日期：2006.12.1

  Aprotic solvents are usually preferred for the SN2 reactions, because nucleophilicity and hence SN2 reactivity are severely retarded by the influence of the partial positive charge of protic solvents. In this work, we introduce a remarkable effect of using tertiary alcohols as a reaction medium for nucleophilic fluorination with alkali metal fluorides. In this novel synthetic method, the nonpolar protic

  SN2 反应通常优选非质子溶剂，因为质子溶剂的部分正电荷的影响严重阻碍了亲核性和 SN2 反应性。在这项工作中，我们介绍了使用叔醇作为碱金属氟化物亲核氟化反应介质的显着效果。在这种新的合成方法中，非极性质子叔醇在没有任何催化剂的情况下显着增强了氟离子的亲核性，大大提高了亲核氟化的速率并减少了副产物（如烯烃、醇或醚）与使用偶极非质子溶剂的常规方法相比。
• A New and Improved Synthesis of the Precursor of the Hypoxia Marker [¹8F]-FMISO
  作者：Julio Álvarez-Builla、Elena Nieto、Ramón Alajarín、Ignacio Larrañaga、Elena Gorospe、Miguel Pozo

  DOI：10.1055/s-0030-1258269

  日期：2010.11

  A new synthetic approach to the precursor of the hypoxia marker [¹8F]-FMISO has been developed. Three different tosylation methods were studied for the preparation of the key intermediate. The overall yield is markedly higher than the yields reported for previous syntheses. The precursor was used to prepare [¹8F]-FMISO and the results were comparable to those obtained when a commercial precursor was used.

  第 V 组金属化合物与三氧化硫的反应
• Azeotropic drying-free aliphatic radiofluorination to produce PET radiotracers in a mixed organic solvent system
  作者：Young-Do Kwon、Jeongmin Son、Mijin Yun、Joong-Hyun Chun

  DOI：10.1016/j.tetlet.2018.06.033

  日期：2018.7

  in various organic solvents for subsequent radiofluorination. Herein, we report the azeotropic drying-free radiofluorination of aliphatic substrates and demonstrate the viability of hydrated [18F]fluoride ions in a mixed organic solvent system for obtaining useful radiochemical yields (RCYs). This practical and simple method has demonstrated general applicability to the production of established PET

  研究了混合有机溶剂体系中有效的脂肪族放射性氟化。此方法避免了大多数氟18正电子发射断层扫描（PET）放射性示踪剂的制备过程中通常需要的耗时的[ 18 F]氟化物干燥步骤。从具有相转移剂的QMA（季铵阴离子交换）盒中洗脱的[ 18 F]氟离子直接混合在各种有机溶剂中，用于随后的放射性氟化。本文中，我们报告了脂肪族底物的共沸无干燥放射性氟化，并证明了水合[ 18混合有机溶剂系统中的F]氟离子，以获得有用的放射化学产率（RCY）。这种实用，简单的方法已证明具有普遍的适用性，可用于既定的PET示踪剂的生产以及早期潜在放射性示踪剂的快速评估和化学优化。
• In Vivo Ester Hydrolysis as a New Approach in Development of Positron Emission Tomography Tracers for Imaging Hypoxia
  作者：Lifang Zhang、Xinyue Yao、Jianhua Cao、Haiyan Hong、Aili Zhang、Ruiyue Zhao、Yan Zhang、Zhihao Zha、Yajing Liu、Jinping Qiao、Lin Zhu、Hank F. Kung

  DOI：10.1021/acs.molpharmaceut.8b01131

  日期：2019.3.4

  condition, while 2-[18F]fluoropropionic acid (2-[18F]FPA) displayed no difference. Biodistribution studies in mice bearing EMT-6 tumor showed that [18F]5, [18F]8, and 2-[18F]FPA displayed similar tumor and major organ uptakes. Tumor uptake values for all three agents were higher than those of [18F]FMISO, respectively ( P < 0.05). This is likely due to a rapid in vivo hydrolysis of [18F]5 and [18F]8 to their

  缺氧是与肿瘤不受控制的生长有关的重要生化和生理状况。测量肿瘤组织中的缺氧可能有助于表征肿瘤进展和监测药物治疗。[18F] FMISO是使用正电子发射断层扫描（PET）对缺氧组织成像的最广泛使用的放射性示踪剂。然而，它在低氧组织中的摄取相对较低，这导致PET图像中目标与背景的对比度较低。为了克服这些缺点，使用了两种新型的2-氟丙酸酯，硝基咪唑衍生物2-氟丙酸2-（2-硝基-咪唑-1-基）-乙基酯（FNPFT，[19F] 5）和2-氟丙酸2-制备并测试了（2-甲基-5-硝基-咪唑-1-基）-乙基酯（FMNPFT，[19F] 8）。[18F] 5和[18F] 8的放射性标记在45分钟内完成（放射化学纯度> 95％，[18F] 5的经衰变校正的放射化学产率为11±2％，[18F] 8的放射性化学产率为13± 2％，n = 5）。使用EMT-6肿瘤细胞进行的体外细胞摄取研究表明，放射性示踪剂[18F]
• Preparation of fluorine-18-labelled fluoromisonidazole using two different synthesis methods
  作者：Eeva-Liisa Kämäräinen、Teija Kyllönen、Outi Nihtilä、Heikki Björk、Olof Solin

  DOI：10.1002/jlcr.795

  日期：2004.1

  18F-labelled fluoromisonidazole [1H-1-(3-[18F]fluoro-2-hydroxypropyl)-2-nitroimida-zole; ([18F]FMISO)] is used as an in vivo marker of hypoxic cells in tumours and ischaemic areas of the heart and the brain. The compound plays an important role in evaluating the oxygenation status in tumours during radiotherapy. In this paper, we report experiments carried out in our laboratory in synthesizing [18F]FMISO using two different methods. The first method (I) for the [18F]FMISO synthesis was the fluorination of (2R)-(−)-glycidyl tosylate to [18F]epifluorohydrin. The subsequent nucleophilic ring opening, achieved with 2-nitroimidazole, leads to labelled FMISO. The second method (II) was the fluorination of the protected precursor 1-(2′-nitro-1′-imidazolyl)-2-O-tetrahydropyranyl-3-O-toluenesulphonyl-propanediol, followed by a rapid removal of the protecting group. With the first method, the radiochemical yield was about 10% at the end of the synthesis (EOS), and the radiochemical purity was over 99%. The radiochemical yield in the second method was 21% (EOS) on an average, and the radiochemical purity was over 97%. When an automated commercial synthesis module was used with method II, slightly better and more reproducible yields were achieved. The improvement in the synthesis yield with the automated apparatus will be valuable when working with high activities, and therefore it is under further development. Copyright © 2003 John Wiley & Sons, Ltd.

  18F 标记的氟咪唑[1H-1-(3-[18F]氟-2-羟基丙基)-2-硝基咪唑；（[18F]FMISO）]被用作肿瘤以及心脏和大脑缺血区域缺氧细胞的体内标记物。该化合物在放疗期间评估肿瘤氧合状态方面发挥着重要作用。本文报告了我们实验室使用两种不同方法合成 [18F]FMISO 的实验。合成[18F]FMISO的第一种方法（I）是将(2R)-(-)-缩水甘油对甲苯磺酸盐氟化为[18F]环氟醇。随后用 2-硝基咪唑进行亲核开环，得到标记的 FMISO。第二种方法（II）是将受保护的前体 1-（2′-硝基-1′-咪唑基）-2-O-四氢吡喃基-3-O-甲苯磺酰基丙二醇氟化，然后迅速去除保护基。采用第一种方法，合成结束时的放射化学收率（EOS）约为 10%，放射化学纯度超过 99%。第二种方法的放射化学收率平均为 21%（EOS），放射化学纯度超过 97%。在第二种方法中使用自动商业合成模块时，产量略高，且可重复性更好。使用自动化设备提高合成产量对高活性工作很有价值，因此正在进一步开发中。Copyright © 2003 John Wiley & Sons, Ltd. All Rights Reserved.