10-[N-(Diethoxyphosphorylmethyl)aminocarbonylmethyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid tri-tert-butyl ester | 294630-04-9

• 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: 10-[N-(Diethoxyphosphorylmethyl)aminocarbonylmethyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid tri-tert-butyl ester
• CAS: 294630-04-9
• 化学式: C₃₃H₆₄N₅O₁₀P
• 分子量: 721.872
• InChiKey: SVPCUVJXWISERI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.57
• 重原子数：
  49.0
• 可旋转键数：
  14.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  156.49
• 氢给体数：
  1.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  10-[N-(Diethoxyphosphorylmethyl)aminocarbonylmethyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid tri-tert-butyl ester 在 三甲基溴硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 10-[N-(Dihydroxyphosphorylmethyl)aminocarbonylmethyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid
  参考文献：
  名称：

  Non-covalent Conjugates between Cationic Polyamino Acids and GdIII Chelates: A Route for Seeking Accumulation of MRI-Contrast Agents at Tumor Targeting Sites

  摘要：

  Three novel Gd chelates containing on their external surface pendant phosphonate and carboxylate groups, which promote the interaction with the positively charged groups of polyornithine and polyarginine, have been synthesized. Their solution structures have been assessed on the basis of H-1- and P-31-NMR spectra of the Eu and Yb analogues. A thorough investigation of the relaxometric (H-1 and O-17) Properties of the Gd chelates has been carried out and the observed relaxivities have been accounted for the sum of three contributions arising from water molecules in the first, second, and outer coordination layers, respectively. It has been found that the occurrence of a tight second coordination coating renders the dissociation of the water molecule directly coordinated to the Gd ion more difficult. The binding interactions between the negatively charged Gd chelates and the positively charged groups of polyornithine (ca. 140 residues) and polyarginine (ca. 204 residues) have been evaluated by means of the proton relaxation enhancement (PRE) method. Although the binding interaction decreases markedly in the presence of competitive anions in the solution medium, the affinity is strong enough that in blood serum it is possible to meet the conditions where most of the chelate is bound to the polyamino acid substrate. On this basis one may envisage a novel route for a MRI location of tumors as it is known that positively charged polyamino acids selectively bind to tumors having a greater negative charge than non-tumor cells.

  DOI：

  10.1002/1521-3765(20000717)6:14<2609::aid-chem2609>3.0.co;2-s
• 作为产物：
  描述：

  diethyl N-benzylaminomethylphosphonate 在 10percent Pd/C sodium hydroxide 、 甲酸铵 、 potassium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 10-[N-(Diethoxyphosphorylmethyl)aminocarbonylmethyl]-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid tri-tert-butyl ester
  参考文献：
  名称：

  Non-covalent Conjugates between Cationic Polyamino Acids and GdIII Chelates: A Route for Seeking Accumulation of MRI-Contrast Agents at Tumor Targeting Sites

  摘要：

  Three novel Gd chelates containing on their external surface pendant phosphonate and carboxylate groups, which promote the interaction with the positively charged groups of polyornithine and polyarginine, have been synthesized. Their solution structures have been assessed on the basis of H-1- and P-31-NMR spectra of the Eu and Yb analogues. A thorough investigation of the relaxometric (H-1 and O-17) Properties of the Gd chelates has been carried out and the observed relaxivities have been accounted for the sum of three contributions arising from water molecules in the first, second, and outer coordination layers, respectively. It has been found that the occurrence of a tight second coordination coating renders the dissociation of the water molecule directly coordinated to the Gd ion more difficult. The binding interactions between the negatively charged Gd chelates and the positively charged groups of polyornithine (ca. 140 residues) and polyarginine (ca. 204 residues) have been evaluated by means of the proton relaxation enhancement (PRE) method. Although the binding interaction decreases markedly in the presence of competitive anions in the solution medium, the affinity is strong enough that in blood serum it is possible to meet the conditions where most of the chelate is bound to the polyamino acid substrate. On this basis one may envisage a novel route for a MRI location of tumors as it is known that positively charged polyamino acids selectively bind to tumors having a greater negative charge than non-tumor cells.

  DOI：

  10.1002/1521-3765(20000717)6:14<2609::aid-chem2609>3.0.co;2-s