{4,10-bis-[(2-benzyloxycarbonylamino-ethylcarbamoyl)methyl]-7-tert-butoxycarbonylmethyl-1,4,7,10-tetraaza-cyclododec-1-yl}-acetic acid tert-butyl ester | 1277166-08-1

• 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: {4,10-bis-[(2-benzyloxycarbonylamino-ethylcarbamoyl)methyl]-7-tert-butoxycarbonylmethyl-1,4,7,10-tetraaza-cyclododec-1-yl}-acetic acid tert-butyl ester
• CAS: 1277166-08-1
• 化学式: C₄₄H₆₈N₈O₁₀
• 分子量: 869.072
• InChiKey: BATKTHBBIJAUSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.98
• 重原子数：
  62.0
• 可旋转键数：
  18.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  200.42
• 氢给体数：
  4.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  {4,10-bis-[(2-benzyloxycarbonylamino-ethylcarbamoyl)methyl]-7-tert-butoxycarbonylmethyl-1,4,7,10-tetraaza-cyclododec-1-yl}-acetic acid tert-butyl ester 在 甲酸 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 60.0~80.0 ℃ 、250.0 kPa 条件下， 反应 54.0h， 生成 (4,10-bis-{[2-(bis-carboxymethyl-amino)-ethylcarbamoyl]methyl}-7-carboxymethyl-1,4,7,10-tetraaza-cyclododec-1-yl)-acetic acid
  参考文献：
  名称：

  Calcium-responsive paramagnetic CEST agents

  摘要：

  The assessment of changes in the extracellular calcium concentration by magnetic resonance imaging would be a valuable biomedical research tool to monitor brain neuronal activity. In this perspective, we report here the synthesis of novel ligands consisting of tetraamide and bisamide derivatives of cyclen, L(1) and L(2), respectively, each bearing imino(diacetate) moieties for Ca(2+) binding. Yb(3+) and Eu(3+) complexes are investigated as chemical exchange saturation transfer (CEST) agents that respond to the presence of Ca(2+). A CEST effect is observed for both YbL(1) and EuL(1) complexes (B = 11.7 T), originating from the slow exchange of the amide protons and those of the coordinated water, respectively, whilst no CEST is detected for complexes of L(2). Upon calcium binding. the CEST effect decreases considerably (from 60% to 20% for YbL(1) and from 35% to 10% for EuL(1)). A similar variation is observed in the presence of Mg(2+). The affinity constants between the lanthanide complexes and the alkaline earth metal ions have been estimated from the variation of the CEST effect to be K(aff)(YbL1) (-Ca) = 8 +/- 2 M(-1), K(aff)(YbL1) (-Mg) = 23 +/- 3 M(-1) and K(aff)(EUL1) (-Ca) = 10 +/- 3 M(-1) These low values imply the coordination of the alkaline earth ions to a single iminodiacetate arm. Ca(2+)/Mg(2+) binding to the lanthanide complexes slows down the exchange of the amide protons on YbL(1) which is responsible for the diminished CEST effect. This has been evidenced by assessing the proton exchange rates from the dependency of the CEST effect on the saturation time and the saturation power, in the absence and in the presence of Ca(2+) and Mg(2+). The applicability of the PARACEST MRI agents for Ca(2+) detection has been evaluated on a 16 T MRI scanner. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.07.023
• 作为产物：
  描述：

  benzyl (2-(2-bromoacetamido)ethyl)carbamate 、 1,7-二-(N-叔丁氧羰基甲基)-1,4,7,10-四氮杂环十二烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以75%的产率得到{4,10-bis-[(2-benzyloxycarbonylamino-ethylcarbamoyl)methyl]-7-tert-butoxycarbonylmethyl-1,4,7,10-tetraaza-cyclododec-1-yl}-acetic acid tert-butyl ester
  参考文献：
  名称：

  Calcium-responsive paramagnetic CEST agents

  摘要：

  The assessment of changes in the extracellular calcium concentration by magnetic resonance imaging would be a valuable biomedical research tool to monitor brain neuronal activity. In this perspective, we report here the synthesis of novel ligands consisting of tetraamide and bisamide derivatives of cyclen, L(1) and L(2), respectively, each bearing imino(diacetate) moieties for Ca(2+) binding. Yb(3+) and Eu(3+) complexes are investigated as chemical exchange saturation transfer (CEST) agents that respond to the presence of Ca(2+). A CEST effect is observed for both YbL(1) and EuL(1) complexes (B = 11.7 T), originating from the slow exchange of the amide protons and those of the coordinated water, respectively, whilst no CEST is detected for complexes of L(2). Upon calcium binding. the CEST effect decreases considerably (from 60% to 20% for YbL(1) and from 35% to 10% for EuL(1)). A similar variation is observed in the presence of Mg(2+). The affinity constants between the lanthanide complexes and the alkaline earth metal ions have been estimated from the variation of the CEST effect to be K(aff)(YbL1) (-Ca) = 8 +/- 2 M(-1), K(aff)(YbL1) (-Mg) = 23 +/- 3 M(-1) and K(aff)(EUL1) (-Ca) = 10 +/- 3 M(-1) These low values imply the coordination of the alkaline earth ions to a single iminodiacetate arm. Ca(2+)/Mg(2+) binding to the lanthanide complexes slows down the exchange of the amide protons on YbL(1) which is responsible for the diminished CEST effect. This has been evidenced by assessing the proton exchange rates from the dependency of the CEST effect on the saturation time and the saturation power, in the absence and in the presence of Ca(2+) and Mg(2+). The applicability of the PARACEST MRI agents for Ca(2+) detection has been evaluated on a 16 T MRI scanner. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.07.023