(Z)-3-ethynylcyclohex-2-enoneoxime | 1224432-91-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (Z)-3-ethynylcyclohex-2-enoneoxime
• 英文别名: (NZ)-N-(3-ethynylcyclohex-2-en-1-ylidene)hydroxylamine
• CAS: 1224432-91-0
• 化学式: C₈H₉NO
• 分子量: 135.166
• InChiKey: ATEYTJIOVWQNSV-HJWRWDBZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  32.6
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-溴吡啶 、 (Z)-3-ethynylcyclohex-2-enoneoxime 在 copper(l) iodide 、 四(三苯基膦)钯 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以85%的产率得到(Z)-3-(pyridin-2-ylethynyl)cyclohex-2-enone 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：

  3-ethynyl-2-cyclohexen-1-one 在 hydroxylamine hydrate 作用下， 以 吡啶 为溶剂， 反应 16.5h， 生成 (Z)-3-ethynylcyclohex-2-enoneoxime 、 (E)-3-ethynylcyclohex-2-enoneoxime
  参考文献：
  名称：

  Development of [18F]-PSS223 as a PET Tracer for Imaging of Metabotropic Glutamate Receptor Subtype 5 (mGluR5)

  摘要：

  代谢型谷氨酸受体亚型5（mGluR5）在大脑中的生理和病理过程中的参与已经得到证实，因此mGluR5已经成为一个重要的药物靶点。[11C]-ABP688是迄今为止临床上最成功的mGluR5正电子发射断层扫描（PET）示踪剂，它可以可视化和定量mGluR5。由于碳-11的半衰期较短，[11C]-ABP688的临床应用仅限于设有现场环流加速器和氟-18（半衰期110分钟）类似物更为实用。基于[11C]-ABP688的结构基元，制备了一种新的衍生物[18F]-PSS223，并评估其作为PET示踪剂在体内外成像mGluR5的效果。我们的结果显示有利的体外结合特性；然而[18F]-PSS223的快速脱氟作用不允许在大鼠脑中可视化mGluR5。

  DOI：

  10.2533/chimia.2012.201

文献信息

• Fluorinated pyridylacetylene derivatives as tracers
  申请人：Eidgenössische Technische Hochschule Zürich (ETH)

  公开号：EP2671872A1

  公开（公告）日：2013-12-11

  The invention relates to a novel compound of formula (I) wherein F is 19F or 18F, in free base or acid addition salt form. In its radioactive form with 18F, the compound is useuful as a marker for radioimaging of brain and peripheral nervous system tissues or other tissues containing mGlu5 receptors in vitro or in vivo.

  这项发明涉及一种化合物，其化学式为（I） 其中F为19F或18F，以自由碱基或酸盐形式存在。在其放射性形式中，使用含有18F的化合物作为大脑和外周神经系统组织或其他体内或体外含有mGlu5受体的组织的放射成像标记物。
• Development of [18F]-PSS223 as a PET Tracer for Imaging of Metabotropic Glutamate Receptor Subtype 5 (mGluR5)
  作者：Selena Milicevic Sephton、Patrick Dennler、Dominique S. Leutwiler、Linjing Mu、Roger Schibli、Stefanie D. Krämer、Simon M. Ametamey

  DOI：10.2533/chimia.2012.201

  日期：——

  Involvement of metabotropic glutamate receptor subtype 5 (mGluR5) in physiological and pathophysiological processes in the brain has been demonstrated, and hence mGluR5 has emerged as an important drug target. [11C]-ABP688 is clinically the most successful mGluR5 positron emission tomography (PET) tracer to date and it allows visualization and quantification of mGluR5. Due to the short half-life of carbon-11, clinical use of [11C]-ABP688 is limited to facilities with an on-site cyclotron and a fluorine-18 (half-life 110 min) analogue would be more practical. Based on the [11C]-ABP688 structural motif, a novel derivative [18F]-PSS223 was prepared and evaluated as a PET tracer for imaging of mGluR5 in vitro and in vivo. Our results show favourable in vitro binding properties; however rapid defluorination of [18F]-PSS223 does not allow visualization of mGluR5 in the rat brain.

  代谢型谷氨酸受体亚型5（mGluR5）在大脑中的生理和病理过程中的参与已经得到证实，因此mGluR5已经成为一个重要的药物靶点。[11C]-ABP688是迄今为止临床上最成功的mGluR5正电子发射断层扫描（PET）示踪剂，它可以可视化和定量mGluR5。由于碳-11的半衰期较短，[11C]-ABP688的临床应用仅限于设有现场环流加速器和氟-18（半衰期110分钟）类似物更为实用。基于[11C]-ABP688的结构基元，制备了一种新的衍生物[18F]-PSS223，并评估其作为PET示踪剂在体内外成像mGluR5的效果。我们的结果显示有利的体外结合特性；然而[18F]-PSS223的快速脱氟作用不允许在大鼠脑中可视化mGluR5。
• Structure−Activity Relationships of Fluorinated (<i>E</i>)-3-((6-Methylpyridin-2-yl)ethynyl)cyclohex-2-enone-<i>O</i>-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)
  作者：Cindy A. Baumann、Linjing Mu、Sinja Johannsen、Michael Honer、Pius A. Schubiger、Simon M. Ametamey

  DOI：10.1021/jm901850k

  日期：2010.5.27

  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.