N-methyl-1-[1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl]methylamine | 1384746-19-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-methyl-1-[1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl]methylamine
• 英文别名: N-methyl-1-[1-[2-(2-methyl-5-nitroimidazol-1-yl)ethyl]triazol-4-yl]methanamine
• CAS: 1384746-19-3
• 化学式: C₁₀H₁₅N₇O₂
• 分子量: 265.275
• InChiKey: JZHFAOMFODDRNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-甲基炔丙基胺 、 1-(2-叠氮乙基)-2-甲基-5-硝基咪唑 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 反应 48.0h， 以47%的产率得到N-methyl-1-[1-(2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl)-1H-1,2,3-triazol-4-yl]methylamine
  参考文献：
  名称：

  Influence of ligand denticity on the properties of novel 99mTc(I)–carbonyl complexes. Application to the development of radiopharmaceuticals for imaging hypoxic tissue

  摘要：

  An important issue in the development of metal-based radiopharmaceuticals is the selection of the labelling strategy in order to couple the metal to the pharmacophore without losing the biological activity. With the aim to evaluate the correlation between ligand denticity and biological behaviour of the corresponding Tc-99m complexes, we designed a tridentate and a bidentate 5-nitroimidazole derivatives suitable for Tc-99m(I) tricarbonyl complexation and with potential use as radiopharmaceuticals towards hypoxic tissue diagnosis. Ligands were synthesized using metronidazol, a pharmaceutical containing the bioreductive pharmacophore as starting material. The chelating units were connected to the pharmacophore using the click reaction of Huisgen. Both Tc-99m complexes were obtained in high yield and were hydrophilic and stable in labelling milieu. The complex obtained from the tridentate ligand exhibited high stability in human plasma, low protein binding and a favourable biodistribution characterized by low blood and liver uptake, fast elimination and negligible uptake in other organs or tissues. Selective uptake and retention in tumour together with favourable tumour/muscle ratio makes this Tc-99m-complex a promising candidate for further evaluation as potential hypoxia imaging agent in tumours. The bidentate ligand, on the other hand, yielded a less stable Tc-99m-complex that experimented hydrolysis in vitro and decomposition in human plasma and showed high protein binding, high blood and liver uptake and moderate excretion. Although selective uptake and retention in tumour was also observed physicochemical and biological behaviour are inadequate for in vivo use, demonstrating that denticity of the ligand is particularly important and that tridentate ligands are preferable in order to prepare Tc-99m-tricarbonyl complexes for Nuclear Medicine imaging. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.05.010

文献信息

• Influence of ligand denticity on the properties of novel 99mTc(I)–carbonyl complexes. Application to the development of radiopharmaceuticals for imaging hypoxic tissue
  作者：Soledad Fernández、Javier Giglio、Ana M. Rey、Hugo Cerecetto

  DOI：10.1016/j.bmc.2012.05.010

  日期：2012.7

  An important issue in the development of metal-based radiopharmaceuticals is the selection of the labelling strategy in order to couple the metal to the pharmacophore without losing the biological activity. With the aim to evaluate the correlation between ligand denticity and biological behaviour of the corresponding Tc-99m complexes, we designed a tridentate and a bidentate 5-nitroimidazole derivatives suitable for Tc-99m(I) tricarbonyl complexation and with potential use as radiopharmaceuticals towards hypoxic tissue diagnosis. Ligands were synthesized using metronidazol, a pharmaceutical containing the bioreductive pharmacophore as starting material. The chelating units were connected to the pharmacophore using the click reaction of Huisgen. Both Tc-99m complexes were obtained in high yield and were hydrophilic and stable in labelling milieu. The complex obtained from the tridentate ligand exhibited high stability in human plasma, low protein binding and a favourable biodistribution characterized by low blood and liver uptake, fast elimination and negligible uptake in other organs or tissues. Selective uptake and retention in tumour together with favourable tumour/muscle ratio makes this Tc-99m-complex a promising candidate for further evaluation as potential hypoxia imaging agent in tumours. The bidentate ligand, on the other hand, yielded a less stable Tc-99m-complex that experimented hydrolysis in vitro and decomposition in human plasma and showed high protein binding, high blood and liver uptake and moderate excretion. Although selective uptake and retention in tumour was also observed physicochemical and biological behaviour are inadequate for in vivo use, demonstrating that denticity of the ligand is particularly important and that tridentate ligands are preferable in order to prepare Tc-99m-tricarbonyl complexes for Nuclear Medicine imaging. (C) 2012 Elsevier Ltd. All rights reserved.