[¹¹C]-copper(I) cyanide.

• 分子结构分类: 无机化合物 - 混合金属/非金属化合物 - 过渡金属有机体
• 英文名称: [¹¹C]-copper(I) cyanide.
• 英文别名: azanylidyne(111C)methane;copper(1+)
• 化学式: CN*Cu
• 分子量: 88.5527
• InChiKey: DOBRDRYODQBAMW-ULWFUOSBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.09
• 重原子数：
  3
• 可旋转键数：
  0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  23.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-2-(3-fluorophenyl)-N-(5-iodopyridin-2-yl)cyclopropanecarboxamide 、 [¹¹C]-copper(I) cyanide. 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.08h， 生成 (1R,2S)-2-(((2,4-dimethylpyrimidin-5-yl)oxy)methyl)-N-(5-[¹¹C]-cyanopyridin-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide
  参考文献：
  名称：

  Synthesis and Evaluation of Novel Radioligands for Positron Emission Tomography Imaging of the Orexin-2 Receptor

  摘要：

  Orexin receptors (OXRs) in the brain have been implicated in diverse physiological and neuropsychiatric conditions. Here we describe the design, synthesis, and evaluation of OXR ligands related to (1R,2S)-2-(((2-methyl-4-methoxymethylpyrimidin-5-yl)oxy)methyl)-N-(5-fluoropyri- din-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide (9a) applicable to positron emission tomography (PET) imaging. Structural features were incorporated to increase binding affinity for OXRs, to enable carbon-11 radiolabeling and to adjust lipophilicity considered optimal for brain penetration and low nonspecific binding. 9a displayed nanomolar affinity for OXRs, and autoradiography using rat brain sections showed that specific binding of [C-11]9a was distributed primarily to neocortical layer VI and hypothalamus, consistent with reported localizations of orexin-2 receptors (OX(2)Rs). In vivo PET study of [C-11]9a demonstrated moderate uptake of radioactivity into rat and monkey brains under deficiency or blockade of P-glycoprotein, and distribution of PET signals in the brain was in agreement with autoradiographic data. Our approach and findings have provided significant information for development of OX2R PET tracers.

  DOI：

  10.1021/jm400772t
• 作为产物：
  描述：

  [11C]hydrogen cyanide 、 copper(II) sulfate 在 sodium metabisulfite 作用下， 以 水 为溶剂， 反应 0.03h， 生成 [¹¹C]-copper(I) cyanide.
  参考文献：
  名称：

  Development of Novel PET Probes for Central 2-Amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic Acid Receptors

  摘要：

  We document the development of PET probes for central AMPA receptors and their application to in vivo animal imaging. An initial screening of perampanel derivatives was performed to identify probe candidates. Despite the high autoradiographic contrast yielded by several radioligands, rat PET scans did not support their in vivo suitability. Further focused derivatization and a second screening by ex vivo LC-MS measurements led to the selection of 2-[1-(3-methylaminophenyl)-2-oxo-5-(pyrimidin-2-yl)1,2-dihydropyridin-3-yl]benzonitrile, 21a, and its analogues as candidates. [C-11]21a was shown by autoradiography to specifically bind to the neocortex and hippocampus, consistent with AMPA receptor localization. PET imaging with [C-11]21a demonstrated moderate uptake of radioactivity in rat and monkey brains, with the retention of radiosignals being consistent with that from the autoradiogram data, and the uptake was blocked by pretreatment with unlabeled 21a in a dose-dependent manner. The current approach has facilitated the discovery of a PET probe potentially suitable for translational research and development focused on AMPA receptors.

  DOI：

  10.1021/acs.jmedchem.5b00712

文献信息

• Development of Novel PET Probes for Central 2-Amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic Acid Receptors
  作者：Norihito Oi、Masaki Tokunaga、Michiyuki Suzuki、Yuji Nagai、Yosuke Nakatani、Noboru Yamamoto、Jun Maeda、Takafumi Minamimoto、Ming-Rong Zhang、Tetsuya Suhara、Makoto Higuchi

  DOI：10.1021/acs.jmedchem.5b00712

  日期：2015.11.12

  We document the development of PET probes for central AMPA receptors and their application to in vivo animal imaging. An initial screening of perampanel derivatives was performed to identify probe candidates. Despite the high autoradiographic contrast yielded by several radioligands, rat PET scans did not support their in vivo suitability. Further focused derivatization and a second screening by ex vivo LC-MS measurements led to the selection of 2-[1-(3-methylaminophenyl)-2-oxo-5-(pyrimidin-2-yl)1,2-dihydropyridin-3-yl]benzonitrile, 21a, and its analogues as candidates. [C-11]21a was shown by autoradiography to specifically bind to the neocortex and hippocampus, consistent with AMPA receptor localization. PET imaging with [C-11]21a demonstrated moderate uptake of radioactivity in rat and monkey brains, with the retention of radiosignals being consistent with that from the autoradiogram data, and the uptake was blocked by pretreatment with unlabeled 21a in a dose-dependent manner. The current approach has facilitated the discovery of a PET probe potentially suitable for translational research and development focused on AMPA receptors.
• Synthesis and Evaluation of Novel Radioligands for Positron Emission Tomography Imaging of the Orexin-2 Receptor
  作者：Norihito Oi、Michiyuki Suzuki、Taro Terauchi、Masaki Tokunaga、Yosuke Nakatani、Noboru Yamamoto、Toshimitsu Fukumura、Ming-Rong Zhang、Tetsuya Suhara、Makoto Higuchi

  DOI：10.1021/jm400772t

  日期：2013.8.22

  Orexin receptors (OXRs) in the brain have been implicated in diverse physiological and neuropsychiatric conditions. Here we describe the design, synthesis, and evaluation of OXR ligands related to (1R,2S)-2-(((2-methyl-4-methoxymethylpyrimidin-5-yl)oxy)methyl)-N-(5-fluoropyri- din-2-yl)-2-(3-fluorophenyl)cyclopropanecarboxamide (9a) applicable to positron emission tomography (PET) imaging. Structural features were incorporated to increase binding affinity for OXRs, to enable carbon-11 radiolabeling and to adjust lipophilicity considered optimal for brain penetration and low nonspecific binding. 9a displayed nanomolar affinity for OXRs, and autoradiography using rat brain sections showed that specific binding of [C-11]9a was distributed primarily to neocortical layer VI and hypothalamus, consistent with reported localizations of orexin-2 receptors (OX(2)Rs). In vivo PET study of [C-11]9a demonstrated moderate uptake of radioactivity into rat and monkey brains under deficiency or blockade of P-glycoprotein, and distribution of PET signals in the brain was in agreement with autoradiographic data. Our approach and findings have provided significant information for development of OX2R PET tracers.