2-fluoro-3-(hex-5-yn-1-yloxy)pyridine | 1174914-26-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-fluoro-3-(hex-5-yn-1-yloxy)pyridine
• 英文别名: 2-fluoro-3-(hex-5-ynyloxy)pyridine；2-Fluoro-3-hex-5-ynoxypyridine
• CAS: 1174914-26-1
• 化学式: C₁₁H₁₂FNO
• 分子量: 193.221
• InChiKey: OKZVBWMVIUPPEW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-benzo[1,3]dioxol-5-yl-4-(3-(2-{2-[2-(2-azidoethoxy)ethoxy]ethoxy}ethoxy)-4,5-dimethoxybenzyl)-5-hydroxy-5-(4-methoxyphenyl)-5H-furan-2-one 、 2-fluoro-3-(hex-5-yn-1-yloxy)pyridine 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以84%的产率得到3-benzo[1,3]-dioxol-5-yl-4-[3-(2-{2-[2-(2-{4-[4-(2-fluoropyridin-3-yloxy)butyl]-1,2,3-triazol-1-yl}ethoxy)ethoxy]ethoxy}ethoxy)-4,5-dimethoxybenzyl]-5-hydroxy-5-(4-methoxyphenyl)-5H-furan-2-one
  参考文献：
  名称：

  正电子发射体层摄影术中内皮素A受体（放射性）配体的开发和评估

  摘要：

  内皮素（ET）受体的表达和功能在心血管疾病，肿瘤进展和肿瘤转移中异常。先前报道的基于非肽ET A受体拮抗剂PD 156707的用于正电子发射断层扫描（PET）的有前途的放射性配体显示出与心肌中靶标受体的特异性结合，但在胆汁和肠中高积累，这可能是由于其高亲脂性。在这项研究中，我们描述了一系列具有亲水结构单元的氟化衍生物的合成。所有化合物被评估为高亲和力ET甲受体配体（16，17，23 - 26，ķ我= 1.4−7.9 nM），并且具有比ET B受体更高的亚型选择性。[ 18 F] 3-苯并[1,3]二氧杂环戊烯-5-基-4- {3- [1-（2- {2- [2-（2-氟乙氧基）乙氧基]乙氧基}乙基）-1- ħ -合成了[1,2,3]三唑-4-基甲氧基] -4,5-二甲氧基苄基} -5-羟基-5-（4-甲氧基苯基）-5 H-呋喃-2-酮（[ 18 F] 17）作为该系列的放射性配体之一，在人血

  DOI：

  10.1021/jm101110w
• 作为产物：
  描述：

  3-(hex-5-ynyloxy)-2-nitropyridine 在 四丁基氟化铵 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以77%的产率得到2-fluoro-3-(hex-5-yn-1-yloxy)pyridine
  参考文献：
  名称：

  Radiosynthesis and bioconjugation of [¹⁸F]FPy5yne, a prosthetic group for the¹⁸F labeling of bioactive peptides

  摘要：

  一种基于18F的新型支架已被制备用于标记叠氮化修饰的多肽，以便在PET成像中使用。2-[18F]氟-3-(己-5-炔氧基)吡啶([18F]FPy5yne，[18F]-1)是通过有效的亲核杂环芳香族取代反应制备的，使用相应的2-硝基(2)或2-三甲基铵三氟甲磺酸盐吡啶(3)。从2中获得的[18F]FPy5yne的最佳放射化学产率为91%(射线TLC，15分钟，110°C，DMSO)。从3中获得的最佳放射化学产率为93%(射线TLC，15分钟，110°C，MeCN)。通过HPLC纯化的[18F]FPy5yne通过CuI介导的Huisgen [3+2]环加成反应与模型多肽N3–(CH2)4–CO–YKRI–OH连接，在铜稳定配体三(苄基三唑基甲基)胺(TBTA)和N,N-二异丙基乙胺(DIEA)的存在下。生物共轭物的放射化学产率平均为89%±8.6%(n=4)，通过放射HPLC判断。从轰击结束时获得的未衰减校正的最佳收集放射化学产率为5.8%(衰减校正后为18.7%)，总制备时间为160分钟。版权所有 © 2008 John Wiley & Sons, Ltd.

  DOI：

  10.1002/jlcr.1561

文献信息

• Inverse 1,2,3-Triazole-1-yl-ethyl Substituted Hydroxamates as Highly Potent Matrix Metalloproteinase Inhibitors: (Radio)synthesis, in Vitro and First in Vivo Evaluation
  作者：Verena Hugenberg、Burkhard Riemann、Sven Hermann、Otmar Schober、Michael Schäfers、Katrin Szardenings、Artem Lebedev、Umesh Gangadharmath、Hartmuth Kolb、Joseph Walsh、Wei Zhang、Klaus Kopka、Stefan Wagner

  DOI：10.1021/jm4006753

  日期：2013.9.12

  Noninvasive imaging and quantification of matrix metalloproteinase (MMP) activity in vivo are of great (pre)clinical interest. This can potentially be realized by using radiolabeled MMP inhibitors (MMPIs) as positron emission tomography (PET) imaging agents. Triazole-substituted MMPIs, discovered by our group, are highly potent inhibitors of MMP-2, -8, -9, and -13. The triazole ring and its position contribute significantly to the potency of the MMP inhibitor. To evaluate structure activity relationships (SARs) of the initially discovered triazole-substituted MMPIs, an additional CH2-group between the backbone of the molecule and the triazole core was inserted, and the triazole ring was "inversed" by switching the alkyne and azide groups. Similar to the original triazole-substituted hydroxamates, the inverse triazole MMPIs are excellent inhibitors with promising in vivo properties. Pharmacokinetic properties and metabolic stability of an F-18-labeled candidate in mice were investigated.
• A New Generation of Radiofluorinated Pyrimidine-2,4,6-triones as MMP-Targeted Radiotracers for Positron Emission Tomography
  作者：Daniela Schrigten、Hans-Jörg Breyholz、Stefan Wagner、Sven Hermann、Otmar Schober、Michael Schäfers、Günter Haufe、Klaus Kopka

  DOI：10.1021/jm201142w

  日期：2012.1.12

  Radiolabeled C-5-disubstituted pyrimidine-2,4,6-triones have recently been suggested by our group as a class of potent matrix metalloproteinase (MMP) targeted radiotracers that can noninvasively visualize activated MMPs by means of positron emission tomography (PET). MMPs belong to the zinc- and calcium-dependent endopeptidases which are involved in the proteolytic degradation of components of the extracellular matrix (ECM) but also are capable of processing and releasing bioactive molecules such as growth factors, proteinase inhibitors, and cytokines. Locally increased levels of activated MMPs modulate and contribute to the progression of various diseases, such as cancer, atherosclerosis, stroke, arthritis, and others. Therefore, activated MMPs are suitable biological targets for the specific and noninvasive visualization of aforementioned pathologies in vivo. On the basis of our recent results, we here describe a series of new fluorinated pyrimidine-2,4,6-triones of the second generation with maintained MAP inhibition potencies (IC50 = 4-605 nM), which are fine-tuned toward more hydrophilic versions, and show the improved biodistribution behavior of one selected radiofluorinated pyrimidine-2,4,6-trione by means of small-animal PET.