(Z)-3-(pyridin-2-ylethynyl)cyclohex-2-enone O-(3-(2-fluoroethoxy)propyl)oxime | 1451015-38-5

• 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 O-(3-(2-fluoroethoxy)propyl)oxime
• 英文别名: (Z)-N-[3-(2-fluoroethoxy)propoxy]-3-(2-pyridin-2-ylethynyl)cyclohex-2-en-1-imine
• CAS: 1451015-38-5
• 化学式: C₁₈H₂₁FN₂O₂
• 分子量: 316.375
• InChiKey: PTUVTYFBBKVLPM-UZYVYHOESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  43.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-((tert-butyldimethylsilyl)oxy)ethyl 3-bromopropanoate 在 potassium fluoride 、 indium(III) bromide 、 四丁基氟化铵 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 氯仿 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 12.15h， 生成 (Z)-3-(pyridin-2-ylethynyl)cyclohex-2-enone O-(3-(2-fluoroethoxy)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

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.