(R)-di-tert-butyl 2,2′-(4-(1-tert-butoxy-5-(2-(3-((2-methylthiazol-4-yl)ethynyl)phenoxy)-ethylamino)-1,5-dioxopentan-2-yl)-10-(2-oxo-2-((5-oxo-5H-chromeno[2,3-b]pyridin-2-yl)methylamino)ethyl)-1,4,7,10-tetraazacyclododecane-1,7-diyl)diacetate | 1497422-17-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮
• 英文名称: (R)-di-tert-butyl 2,2′-(4-(1-tert-butoxy-5-(2-(3-((2-methylthiazol-4-yl)ethynyl)phenoxy)-ethylamino)-1,5-dioxopentan-2-yl)-10-(2-oxo-2-((5-oxo-5H-chromeno[2,3-b]pyridin-2-yl)methylamino)ethyl)-1,4,7,10-tetraazacyclododecane-1,7-diyl)diacetate
• CAS: 1497422-17-9
• 化学式: C₅₈H₇₆N₈O₁₁S
• 分子量: 1093.35
• InChiKey: ZVLAACKXJMLGMH-QZNUWAOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.71
• 重原子数：
  78.0
• 可旋转键数：
  17.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  215.28
• 氢给体数：
  2.0
• 氢受体数：
  18.0

反应信息

• 作为反应物：
  描述：

  (R)-di-tert-butyl 2,2′-(4-(1-tert-butoxy-5-(2-(3-((2-methylthiazol-4-yl)ethynyl)phenoxy)-ethylamino)-1,5-dioxopentan-2-yl)-10-(2-oxo-2-((5-oxo-5H-chromeno[2,3-b]pyridin-2-yl)methylamino)ethyl)-1,4,7,10-tetraazacyclododecane-1,7-diyl)diacetate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以32%的产率得到(R)-2,2′-(4-(1-carboxy-4-(2-(3-((2-methylthiazol-4-yl)ethynyl)-phenoxy)ethylamino)-4-oxobutyl)-10-(2-oxo-2-((5-oxo-5H-chromeno[2,3-b]pyridin-2-yl)methylamino)ethyl)-1,4,7,10-tetraazacyclododecane-1,7-diyl)diacetic acid
  参考文献：
  名称：

  Microscopic Visualization of Metabotropic Glutamate Receptors on the Surface of Living Cells Using Bifunctional Magnetic Resonance Imaging Probes

  摘要：

  A series of bimodal metabotropic glutamate-receptor targeted MRI contrast agents has been developed and evaluated, based on established competitive metabotropic Glu receptor subtype 5 (mGluR(5)) antagonists. In order to directly visualize mGluR(5) binding of these agents on the surface of live astrocytes, variations in the core structure were made. A set of gadolinium conjugates containing either a cyanine dye or a fluorescein moiety was accordingly prepared, to allow visualization by optical microscopy in cellulo. In each case, surface receptor binding was compromised and cell internalization observed. Another approach, examining the location of a terbium analogue via sensitized emission, also exhibited nonspecific cell uptake in neuronal cell line models. Finally, biotin derivatives of two lead compounds were prepared, and the specificity of binding to the mGluR(5) cell surface receptors was demonstrated with the aid of their fluorescently labeled avidin conjugates, using both total internal reflection fluorescence (TIRF) and confocal microscopy.

  DOI：

  10.1021/cn400175m
• 作为产物：
  描述：

  2-(aminomethyl)-5H-chromeno[2,3-b]pyridin-5-one 在 N-甲基吗啉 、 1-羟基苯并三唑 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 12.25h， 生成 (R)-di-tert-butyl 2,2′-(4-(1-tert-butoxy-5-(2-(3-((2-methylthiazol-4-yl)ethynyl)phenoxy)-ethylamino)-1,5-dioxopentan-2-yl)-10-(2-oxo-2-((5-oxo-5H-chromeno[2,3-b]pyridin-2-yl)methylamino)ethyl)-1,4,7,10-tetraazacyclododecane-1,7-diyl)diacetate
  参考文献：
  名称：

  Microscopic Visualization of Metabotropic Glutamate Receptors on the Surface of Living Cells Using Bifunctional Magnetic Resonance Imaging Probes

  摘要：

  A series of bimodal metabotropic glutamate-receptor targeted MRI contrast agents has been developed and evaluated, based on established competitive metabotropic Glu receptor subtype 5 (mGluR(5)) antagonists. In order to directly visualize mGluR(5) binding of these agents on the surface of live astrocytes, variations in the core structure were made. A set of gadolinium conjugates containing either a cyanine dye or a fluorescein moiety was accordingly prepared, to allow visualization by optical microscopy in cellulo. In each case, surface receptor binding was compromised and cell internalization observed. Another approach, examining the location of a terbium analogue via sensitized emission, also exhibited nonspecific cell uptake in neuronal cell line models. Finally, biotin derivatives of two lead compounds were prepared, and the specificity of binding to the mGluR(5) cell surface receptors was demonstrated with the aid of their fluorescently labeled avidin conjugates, using both total internal reflection fluorescence (TIRF) and confocal microscopy.

  DOI：

  10.1021/cn400175m