(E)-3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone oxime

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (E)-3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone oxime
• 英文别名: (NE)-N-[3-[2-(6-methylpyridin-2-yl)ethynyl]cyclohex-2-en-1-ylidene]hydroxylamine
• 化学式: C₁₄H₁₄N₂O
• 分子量: 226.278
• InChiKey: UWOHEEOCHCCCNH-JQIJEIRASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  45.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone oxime 、 2,6-二氟吡啶 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 2.0h， 以45%的产率得到(E)-3-((6-methylpyridin-2-yl)ethynyl)cyclohex-2-enone O-6-fluoropyridin-2-yl oxime
  参考文献：
  名称：

  Structure−Activity Relationships of Fluorinated (E)-3-((6-Methylpyridin-2-yl)ethynyl)cyclohex-2-enone-O-methyloxime (ABP688) Derivatives and the Discovery of a High Affinity Analogue as a Potential Candidate for Imaging Metabotropic Glutamate Recepors Subtype 5 (mGluR5) with Positron Emission Tomography (PET)

  摘要：

  The metabotropic glutamate receptor subtype 5 (mGluR5) is recognized to be involved in numerous brain disorders. In an effort to obtain a fluorine-18 labeled analogue of the mGluR5 PET tracer [C-11]ABP688, 13 novel ligands based on the core structure of ABP688 were synthesized. Molecules in which the methyl group at the oxime functionality of ABP688 was replaced by fluorobenzonitriles, fluoropyridines, and fluorinated oxygen containing alkyl side chains were investigated. Substituents at the oxime functionality are well tolerated and resulted in five candidates with K-i values below 10 nM. The most promising candidate, (E)-3-(pyridin-2-ylethynyl)cyclohex-2-enone-O-2-(2-fluoroethoxy)-ethyloxime (38, K-i = 3.8 nM), was radiolabeled with fluorine-18. Scatchard analysis of [F-18]38 which modeled best for two sites pointed to high binding affinity (K-D1 = 0.61 +/- 0.19 nM and K-D2 = 13.73 +/- 4.69 nM) too. These data strongly suggest the further evaluation of [F-18]38 as a candidate for imaging the mGluR5.

  DOI：

  10.1021/jm901850k
• 作为产物：
  描述：

  2-乙炔-6-甲基吡啶 在 bis-triphenylphosphine-palladium(II) chloride 吡啶 、 copper(l) iodide 、 盐酸羟胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 (E)-3-(6-methylpyridin-2-ylethynyl)cyclohex-2-enone oxime
  参考文献：
  名称：

  ABP688, a novel selective and high affinity ligand for the labeling of mGlu5 receptors: Identification, in vitro pharmacology, pharmacokinetic and biodistribution studies

  摘要：

  [C-11]ABP688 (2) has recently been demonstrated to be a useful PET tracer for in vivo imaging of the metabotropic glutamate receptors type 5 (mGluR5) in rodents. We describe here the identification and preclinical profiling of ABP688 and its tritiated version [H-3]ABP688, and show that its high affinity (K-d = 2 nM), selectivity, and pharmacokinetic properties fulfill all requirements for development as a PET tracer for clinical imaging of the mGlu5 receptor. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.038

文献信息

• [EN] PYRIDYLACETYLENES FOR USE AS RADIOTRACERS AND IMAGING AGENTS<br/>[FR] PYRIDYLACETYLENES A UTILISER COMME RADIO-INDICATEURS ET AGENTS D'IMAGERIE
  申请人：NOVARTIS AG

  公开号：WO2005030723A1

  公开（公告）日：2005-04-07

  The present invention relates to novel pyridylacetylene derivatives of formula I, their Preparation, their use as radiotracers/markers and compositions containing them.

  本发明涉及一种新型的具有化学式I的吡啶基乙炔衍生物，其制备方法，作为放射示踪剂/标记物的用途以及含有它们的组合物。
• Radiosynthesis of the diastereomerically pure (<i>E</i> )-[¹¹ C]ABP688
  作者：Hussein Bdair、I-Huang Tsai、Kelly Smart、Chawki Benkelfat、Marco Leyton、Alexey Kostikov

  DOI：10.1002/jlcr.3802

  日期：2019.10

  We report an efficient protocol for the radiosynthesis of diastereomerically pure (E)-[11C]ABP688, a positron emission tomography (PET) tracer for metabotropic glutamate type 5 (mGlu5) receptor imaging. The protocol reliably provides sterile and pyrogen-free formulation of (E)-[11C]ABP688 suitable for preclinical and clinical PET imaging with >99% diastereomeric excess (d.e.), >99% overall radiochemical purity (RCP), 14.9 ± 4.3% decay-corrected radiochemical yield (RCY), and 148.86 ± 79.8 GBq/μmol molar activity in 40 minutes from the end of bombardment.

  我们报告了一种用于代谢谷氨酸 5 型（mGlu5）受体成像的正电子发射断层扫描（PET）示踪剂--非对映纯(E)-[11C]ABP688 的高效放射合成方案。该方案能可靠地提供无菌、无热原的(E)-[11C]ABP688制剂，适用于临床前和临床PET成像，非对映过量（d.e.）>99%，总体放射化学纯度（RCP）>99%，衰变校正放射化学产率（RCY）为14.9 ± 4.3%，轰击结束后40分钟内摩尔活度为148.86 ± 79.8 GBq/μmol。
• Pyridylacetylenes for Use as Radiotracers and Imaging Agents
  申请人：Gasparini Fabrizio

  公开号：US20090010838A1

  公开（公告）日：2009-01-08

  The present invention relates to novel pyridylacetylene derivatives of formula I their preparation, their use as radio-traces/markers and compositions containing them.

  本发明涉及一种新型的式I的吡啶基乙炔衍生物，它们的制备方法、它们作为放射性示踪剂/标记剂的用途以及包含它们的组合物。
• PYRIDYLACETYLENES FOR USE AS RADIOTRACERS AND IMAGING AGENTS
  申请人：Novartis AG

  公开号：EP1670762B1

  公开（公告）日：2012-12-05
• US8674110B2
  申请人：——

  公开号：US8674110B2

  公开（公告）日：2014-03-18