2-[(2S,5R,8S,11S)-8-[4-[[2-[11-(carboxymethyl)-1,4,8,11-tetrazabicyclo[6.6.3]heptadecan-4-yl]acetyl]amino]butyl]-11-[3-(diaminomethylideneamino)propyl]-5-[(4-hydroxyphenyl)methyl]-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid | 1276543-69-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-[(2S,5R,8S,11S)-8-[4-[[2-[11-(carboxymethyl)-1,4,8,11-tetrazabicyclo[6.6.3]heptadecan-4-yl]acetyl]amino]butyl]-11-[3-(diaminomethylideneamino)propyl]-5-[(4-hydroxyphenyl)methyl]-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid
• CAS: 1276543-69-1
• 化学式: C₄₄H₇₁N₁₃O₁₁
• 分子量: 958.128
• InChiKey: GAGDRTIBTPTHNJ-KMSCUOMXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.6
• 重原子数：
  68
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.66
• 拓扑面积：
  347
• 氢给体数：
  11
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  2-[(2S,5R,8S,11S)-8-[4-[[2-[11-(carboxymethyl)-1,4,8,11-tetrazabicyclo[6.6.3]heptadecan-4-yl]acetyl]amino]butyl]-11-[3-(diaminomethylideneamino)propyl]-5-[(4-hydroxyphenyl)methyl]-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid 、 copper dichloride 在 ammonium acetate 作用下， 以 水 为溶剂， 反应 1.0h， 生成
  参考文献：
  名称：

  High in Vivo Stability of ⁶⁴Cu-Labeled Cross-Bridged Chelators Is a Crucial Factor in Improved Tumor Imaging of RGD Peptide Conjugates

  摘要：

  Although the importance of bifunctional chelators (BFCs) is well recognized, the chemophysical parameters of chelators that govern the biological behavior of the corresponding bioconjugates have not been clearly elucidated. Here, five BFCs closely related in structure were conjugated with a cyclic RGD peptide and radiolabeled with Cu-64 ions. Various biophysical and chemical properties of the Cu(II) complexes were analyzed with the aim of identifying correlations between individual factors and the biological behavior of the conjugates. Tumor uptake and body clearance of the Cu-64-labeled bioconjugates were directly compared by animal PET imaging in animal models, which was further supported by biodistribution studies. Conjugates containing propylene cross-bridged chelators showed higher tumor uptake, while a closely related ethylene cross-bridged analogue exhibited rapid body clearance. High in vivo stability of the copper-chelator complex was strongly correlated with high tumor uptake, while the overall lipophilicity of the bioconjugate affected both tumor uptake and body clearance.

  DOI：

  10.1021/acs.jmedchem.7b01671
• 作为产物：
  描述：

  1,4,8,11-四氮环[9.3.1.1(4,8)]十六烷 在 palladium 10% on activated carbon 氢气 、 sodium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 甲苯 、 乙腈 为溶剂， 反应 190.0h， 生成 2-[(2S,5R,8S,11S)-8-[4-[[2-[11-(carboxymethyl)-1,4,8,11-tetrazabicyclo[6.6.3]heptadecan-4-yl]acetyl]amino]butyl]-11-[3-(diaminomethylideneamino)propyl]-5-[(4-hydroxyphenyl)methyl]-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid
  参考文献：
  名称：

  NOVEL TETRA-AZA MACROCYCLIC COMPOUND, METHOD FOR PREPARING SAME, AND USE THEREOF

  摘要：

  公开号：

  EP2476683B1

文献信息

• NOVEL TETRAAZA MACROCYCLIC COMPOUND, PREPARATION METHOD THEREOF AND USE THEREOF
  申请人：Yoo Jeong Soo

  公开号：US20120219495A1

  公开（公告）日：2012-08-30

  Provided are a cross-bridged tetraaza macrocyclic compound of a novel structure that can be used, for example, as a contrast agent for diagnostic imaging or a radiopharmaceutical and a method for preparing the same. The disclosed tetraaza macrocyclic compound is able to form a stable metal complex at a lower temperature and allows easy conjugation with a bioactive substance or a chemically active substance, when compared to the existing cross-bridged tetraaza macrocyclic compounds.

  提供的是一种新结构的交桥四氮杂大环化合物，可用作诊断成像的造影剂或放射性药物，以及一种制备该化合物的方法。所披露的四氮杂大环化合物能够在较低温度下形成稳定的金属配合物，并且与生物活性物质或化学活性物质相比，易于共轭。
• US9061078B2
  申请人：——

  公开号：US9061078B2

  公开（公告）日：2015-06-23
• US9353120B2
  申请人：——

  公开号：US9353120B2

  公开（公告）日：2016-05-31
• NOVEL TETRA-AZA MACROCYCLIC COMPOUND, METHOD FOR PREPARING SAME, AND USE THEREOF
  申请人：Kyungpook National University Industry- Academic Cooperation Foundation

  公开号：EP2476683B1

  公开（公告）日：2019-04-03
• High in Vivo Stability of ⁶⁴Cu-Labeled Cross-Bridged Chelators Is a Crucial Factor in Improved Tumor Imaging of RGD Peptide Conjugates
  作者：Swarbhanu Sarkar、Nikunj Bhatt、Yeong Su Ha、Phuong Tu Huynh、Nisarg Soni、Woonghee Lee、Yong Jin Lee、Jung Young Kim、Darpan N. Pandya、Gwang Il An、Kyo Chul Lee、Yongmin Chang、Jeongsoo Yoo

  DOI：10.1021/acs.jmedchem.7b01671

  日期：2018.1.11

  Although the importance of bifunctional chelators (BFCs) is well recognized, the chemophysical parameters of chelators that govern the biological behavior of the corresponding bioconjugates have not been clearly elucidated. Here, five BFCs closely related in structure were conjugated with a cyclic RGD peptide and radiolabeled with Cu-64 ions. Various biophysical and chemical properties of the Cu(II) complexes were analyzed with the aim of identifying correlations between individual factors and the biological behavior of the conjugates. Tumor uptake and body clearance of the Cu-64-labeled bioconjugates were directly compared by animal PET imaging in animal models, which was further supported by biodistribution studies. Conjugates containing propylene cross-bridged chelators showed higher tumor uptake, while a closely related ethylene cross-bridged analogue exhibited rapid body clearance. High in vivo stability of the copper-chelator complex was strongly correlated with high tumor uptake, while the overall lipophilicity of the bioconjugate affected both tumor uptake and body clearance.