(Z)-3-(pyridin-2-ylethynyl)cyclohex-2-enone oxime | 1224432-93-2

• 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: (Z)-3-(pyridin-2-ylethynyl)cyclohex-2-enone oxime
• 英文别名: (NZ)-N-[3-(2-pyridin-2-ylethynyl)cyclohex-2-en-1-ylidene]hydroxylamine
• CAS: 1224432-93-2
• 化学式: C₁₃H₁₂N₂O
• 分子量: 212.251
• InChiKey: ZWBSNTSHJZOYAE-SQFISAMPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 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：

  (Z)-3-(pyridin-2-ylethynyl)cyclohex-2-enone oxime 在 四丁基氟化铵 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 4.5h， 生成 (Z)-3-(pyridin-2-ylethynyl)cyclohex-2-enone O-(3-(2-hydroxyethoxy)propyl)oxime
  参考文献：
  名称：

  Synthesis and In Vitro Evaluation of E- and Z-Geometrical Isomers of PSS232 as Potential Metabotropic Glutamate Receptors Subtype 5 (mGlu5) Binders

  摘要：

  Based on the core structure of [C-11]-ABP688, our group developed a novel fluorine-18 labeled PET radiotracer, (E)-[F-18]-PSS232, with significantly improved in vivo properties compared to the earlier fluorine-18 derivative [F-18]-FDEGPECO. The synthetic approach used to obtain PSS232 and the radiolabeling precursor mesylate is disclosed as well as the evaluation of the two geometrical isomers of PSS232. In vitro displacement assays showed higher binding affinity of the E-geometrical isomer (1 nM vs 15 nM, for Z-isomer), which was, for this reason, selected for radiolabeling. One-step radiolabeling conditions (K-222/F-18(-), DMSO, 95 degrees C, 10 min) to synthesize (E)-[F-18]- PSS232 from the mesylate via nucleophilic substitution are described. At ambient temperature, (E)-[F-18]-PSS232, with log D-7.4 value of 2.0, was chemically stable over six hours in the presence of sodium ascorbate as a radical scavenger.

  DOI：

  10.1055/s-0033-1338843
• 作为产物：
  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

文献信息

• Synthesis and In Vitro Evaluation of E- and Z-Geometrical Isomers of PSS232 as Potential Metabotropic Glutamate Receptors Subtype 5 (mGlu5) Binders
  作者：Selena Milicevic Sephton、Simon Ametamey、Linjing Mu、Martina Dragic、Stefanie Krämer、Roger Schibli

  DOI：10.1055/s-0033-1338843

  日期：——

  Based on the core structure of [C-11]-ABP688, our group developed a novel fluorine-18 labeled PET radiotracer, (E)-[F-18]-PSS232, with significantly improved in vivo properties compared to the earlier fluorine-18 derivative [F-18]-FDEGPECO. The synthetic approach used to obtain PSS232 and the radiolabeling precursor mesylate is disclosed as well as the evaluation of the two geometrical isomers of PSS232. In vitro displacement assays showed higher binding affinity of the E-geometrical isomer (1 nM vs 15 nM, for Z-isomer), which was, for this reason, selected for radiolabeling. One-step radiolabeling conditions (K-222/F-18(-), DMSO, 95 degrees C, 10 min) to synthesize (E)-[F-18]- PSS232 from the mesylate via nucleophilic substitution are described. At ambient temperature, (E)-[F-18]-PSS232, with log D-7.4 value of 2.0, was chemically stable over six hours in the presence of sodium ascorbate as a radical scavenger.
• 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.