N,N′-[6-(methoxycarbonyl)pyridin-2-yl]methyl-N,N′-propargyl-1,2-diaminoethane | 1404288-23-8

• 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′-[6-(methoxycarbonyl)pyridin-2-yl]methyl-N,N′-propargyl-1,2-diaminoethane
• CAS: 1404288-23-8
• 化学式: C₂₄H₂₆N₄O₄
• 分子量: 434.495
• InChiKey: IVHRPBVLTFZGNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.62
• 重原子数：
  32.0
• 可旋转键数：
  11.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  84.86
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  N,N′-[6-(methoxycarbonyl)pyridin-2-yl]methyl-N,N′-propargyl-1,2-diaminoethane 、 copper(II) acetate monohydrate 、 苄基叠氮 在 sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 反应 16.0h， 生成 [Cu(N,N′-[1-benzyl-1,2,3-triazole-4-yl]methyl-N,N′-[6-(carboxy)-pyridin-2-yl]-1,2-diaminoethane(-2H))]
  参考文献：
  名称：

  H₂azapa: a Versatile Acyclic Multifunctional Chelator for ⁶⁷Ga, ⁶⁴Cu, ¹¹¹In, and ¹⁷⁷Lu

  摘要：

  Preliminary experiments with the novel acyclic triazole-containing bifunctional chelator H(2)azapa and the radiometals Cu-64, Ga-67, In-111, and Lu-177 have established its significant versatile potential as an alternative to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for metal-based radiopharmaceuticals. Unlike DOTA, H(2)azapa radiolabels quantitatively with Cu-64, Ga-67, In-111, and Lu-177 in 10 min at room temperature. In vitro competition experiments with human blood serum show that Cu-64 remained predominantly chelate-bound, with only 2% transchelated to serum proteins after 20 h. Biodistribution experiments with [Cu-64(azapa)] in mice reveal uptake in various organs, particularly in the liver, lungs, heart, intestines, and kidneys. When compared to [Cu-64(DOTA)](2-), the lipophilic neutral [Cu-64(azapa)] was cleared through the gastrointestinal tract and accumulated in the liver, which is common for lipophilic compounds or free Cu-64. The chelator H(2)azapa is a. model complex for a click-based bifunctional chelating agent, and the lipophilic benzyl "place-holders" will be replaced by hydrophilic peptides to modulate the pharmacokinetics and direct activity away from the liver and gut. The solid-state molecular structure of [In(azapa)(H2O)][ClO4] reveals a very rare eight-coordinate distorted square antiprismatic geometry with one triazole arm bound, and the structure of [Cu-64(azapa)] shows a distorted octahedral geometry. The present study demonstrates significant potential for bioconjugates of H(2)azapa as alternatives to DOTA in copper based radiopharmaceuticals, with the highly modular and "clickable" molecular scaffold of H(2)azapa easily modified into a variety of bioconjugates. H(2)azapa is a versatile addition to the "pa" family, joining the previously published H(2)dedpa (Ga-67/68 and Cu-64), H(4)octapa (In-111, Lu-177, and Y-90), and H(5)decapa (Ac-225) to cover a wide range of important nuclides.

  DOI：

  10.1021/ic302225z
• 作为产物：
  描述：

  N,N′-propargyl-1,2-diaminoethane 、 2-溴甲基-6-吡啶甲酸甲酯 在 sodium carbonate 作用下， 以 乙腈 为溶剂， 反应 48.0h， 以62%的产率得到N,N′-[6-(methoxycarbonyl)pyridin-2-yl]methyl-N,N′-propargyl-1,2-diaminoethane
  参考文献：
  名称：

  H₂azapa: a Versatile Acyclic Multifunctional Chelator for ⁶⁷Ga, ⁶⁴Cu, ¹¹¹In, and ¹⁷⁷Lu

  摘要：

  Preliminary experiments with the novel acyclic triazole-containing bifunctional chelator H(2)azapa and the radiometals Cu-64, Ga-67, In-111, and Lu-177 have established its significant versatile potential as an alternative to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) for metal-based radiopharmaceuticals. Unlike DOTA, H(2)azapa radiolabels quantitatively with Cu-64, Ga-67, In-111, and Lu-177 in 10 min at room temperature. In vitro competition experiments with human blood serum show that Cu-64 remained predominantly chelate-bound, with only 2% transchelated to serum proteins after 20 h. Biodistribution experiments with [Cu-64(azapa)] in mice reveal uptake in various organs, particularly in the liver, lungs, heart, intestines, and kidneys. When compared to [Cu-64(DOTA)](2-), the lipophilic neutral [Cu-64(azapa)] was cleared through the gastrointestinal tract and accumulated in the liver, which is common for lipophilic compounds or free Cu-64. The chelator H(2)azapa is a. model complex for a click-based bifunctional chelating agent, and the lipophilic benzyl "place-holders" will be replaced by hydrophilic peptides to modulate the pharmacokinetics and direct activity away from the liver and gut. The solid-state molecular structure of [In(azapa)(H2O)][ClO4] reveals a very rare eight-coordinate distorted square antiprismatic geometry with one triazole arm bound, and the structure of [Cu-64(azapa)] shows a distorted octahedral geometry. The present study demonstrates significant potential for bioconjugates of H(2)azapa as alternatives to DOTA in copper based radiopharmaceuticals, with the highly modular and "clickable" molecular scaffold of H(2)azapa easily modified into a variety of bioconjugates. H(2)azapa is a versatile addition to the "pa" family, joining the previously published H(2)dedpa (Ga-67/68 and Cu-64), H(4)octapa (In-111, Lu-177, and Y-90), and H(5)decapa (Ac-225) to cover a wide range of important nuclides.

  DOI：

  10.1021/ic302225z