N,N-Bis(3-benzyloxy-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)carboxamido-ethyl-N-(2-aminoethyl)amine (Bn-TREN-Bis-Me-3,2-HOPO) | 186834-28-6

• 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: N,N-Bis(3-benzyloxy-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)carboxamido-ethyl-N-(2-aminoethyl)amine (Bn-TREN-Bis-Me-3,2-HOPO)
• 英文别名: N,N-bis(3-benzyloxy-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)carboxamido-ethyl-N-(2-aminoethyl)amine；TREN(1-Me-HOPO)2；N-[2-[2-aminoethyl-[2-[(1-methyl-2-oxo-3-phenylmethoxypyridine-4-carbonyl)amino]ethyl]amino]ethyl]-1-methyl-2-oxo-3-phenylmethoxypyridine-4-carboxamide
• CAS: 186834-28-6
• 化学式: C₃₄H₄₀N₆O₆
• 分子量: 628.728
• InChiKey: MIAAMAXTYDOERN-UHFFFAOYSA-N

物化性质

• 沸点：
  908.8±65.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  46
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  147
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N,N-Bis(3-benzyloxy-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)carboxamido-ethyl-N-(2-aminoethyl)amine (Bn-TREN-Bis-Me-3,2-HOPO) 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 33.0h， 生成 (2-{2,3-Bis-benzyloxy-4-[2-(bis-{2-[(3-benzyloxy-1-methyl-2-oxo-1,2-dihydro-pyridine-4-carbonyl)-amino]-ethyl}-amino)-ethylcarbamoyl]-benzoylamino}-ethyl)-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Tuning the Coordination Number of Hydroxypyridonate-Based Gadolinium Complexes:  Implications for MRI Contrast Agents

  摘要：

  Eight-coordinate hydroxypyridinone/terephthalamide GdIII complexes display high relaxivities due to their two inner sphere water molecules. This relaxivity can be further increased by functionalizing the terephthalamide moiety with an amine. A significant hydrogen bonding interaction between the amine and another water molecule close to the GdIII apparently facilitates its coordination on the open site of the metal. The resulting nine-coordinate complex has three inner sphere water molecules, while maintaining high stability and fast ligand exchange rates.

  DOI：

  10.1021/ja057805x
• 作为产物：
  描述：

  三(2-氨基乙基)胺 、 3-(benzyloxy)-1-methyl-4-(2-thioxothiazolidine-3-carbonyl)pyridine-2(1H)-one 以 氯仿 为溶剂， 反应 96.0h， 生成 N,N-Bis(3-benzyloxy-1-methyl-2-oxo-1,2-dihydropyridin-4-yl)carboxamido-ethyl-N-(2-aminoethyl)amine (Bn-TREN-Bis-Me-3,2-HOPO)
  参考文献：
  名称：

  静电在免疫蛋白 Siderocalin1 识别铁载体中的作用

  摘要：

  大多数细菌病原体的毒力都需要铁，其中许多病原体依赖铁载体、小分子螯合剂来清除哺乳动物宿主中的铁。作为一种免疫反应，人类蛋白质 Siderocalin 结合载脂蛋白和三价铁载体，以拦截铁向细菌的输送，从而阻止毒力。将空间冲突引入铁载体结构是逃避螯合的重要机制。然而，在不存在空间不相容性的情况下，静电相互作用决定了铁钙素结合铁载体的强度。通过使用一系列等排肠杆菌素类似物，静电相互作用（包括电荷-电荷和阳离子-pi）对 2,3-儿茶酚酸铁载体的识别的贡献已被解卷积。研究中使用的类似物在三（2-氨基乙基）胺（tren）骨架上结合了 2,3-儿茶酚酰胺（CAM）和 N-羟基吡啶（1,2-HOPO）结合单元的系统组合，[tren(CAM) )(m)(1,2-HOPO)(n)，其中 m = 0、1、2 或 3 且 n = 3 - m]。通过小分子晶体学确定合成类似物系列的形状互补性，并通过基于荧光的结合

  DOI：

  10.1021/ja8074665

文献信息

• Hydroxypyridonate and hydroxypyrimidinone chelating agents
  申请人：Raymond N. Kenneth

  公开号：US20050008570A1

  公开（公告）日：2005-01-13

  The present invention provides hydroxypyridinone and hydroxypyrimidone chelating agents. Also provides are Gd(III) complexes of these agents, which are useful as contrast enhancing agents for magnetic resonance imaging. The invention also provides methods of preparing the compounds of the invention, as well as methods of using the compounds in magnetic resonance imaging applications.

  本发明提供了羟基吡啶酮和羟基嘧啶酮螯合剂。还提供了这些剂的Gd(III)配合物，这些配合物可用作磁共振成像的造影增强剂。该发明还提供了制备本发明化合物的方法，以及在磁共振成像应用中使用这些化合物的方法。
• WO2007/121453
  申请人：——

  公开号：——

  公开（公告）日：——
• Multivalent, High-Relaxivity MRI Contrast Agents Using Rigid Cysteine-Reactive Gadolinium Complexes
  作者：Praveena D. Garimella、Ankona Datta、Dante W. Romanini、Kenneth N. Raymond、Matthew B. Francis

  DOI：10.1021/ja204516p

  日期：2011.9.21

  MRI contrast agents providing very high relaxivity values can be obtained through the attachment of multiple gadolinium(III) complexes to the interior surfaces of genome-free viral capsids. In previous studies, the contrast enhancement was predicted to depend on the rigidity of the linker attaching the MRI agents to the protein surface. To test this hypothesis, a new set of Gd-hydroxypyridonate based MRI agents was prepared and attached to genetically introduced cysteine residues through flexible and rigid linkers. Greater contrast enhancements were seen for MRI agents that were attached via rigid linkers, validating the design concept and outlining a path for future improvements of nanoscale MRI contrast agents.
• 3-HYDROXY-2(1H)-PYRIDINONE CHELATING AGENTS
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：EP0840727B1

  公开（公告）日：2004-05-06
• Dendrimeric Gadolinium Chelate with Fast Water Exchange and High Relaxivity at High Magnetic Field Strength
  作者：Valérie C. Pierre、Mauro Botta、Kenneth N. Raymond

  DOI：10.1021/ja045263y

  日期：2005.1.1

  The synthesis and relaxivity properties of a new dendrimeric Gd chelate, Gd-TREN-bisHOPO-TAM-Asp-Asp2-12OH, are presented. The macromolecule demonstrates improved water solubility due to its 12 terminal hydroxyl groups and improved relaxivity due to its optimal water exchange rate and slower molecular tumbling. Unprecedented high relaxivity (r1p = 18 mM-1 s-1) is observed at high magnetic field (90 MHz), an important advance in the development of contrast agents for the next generation of MRI scanners.