2-(2-hydroxy-3-(2-nitro-1H-imidazol-1-yl)propyl)-N,N'-bis(tert-butyloxycarbonyl)-1,3-propanediamine | 159591-78-3

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: 2-(2-hydroxy-3-(2-nitro-1H-imidazol-1-yl)propyl)-N,N'-bis(tert-butyloxycarbonyl)-1,3-propanediamine
• 英文别名: N,N'-di-t-boc-2-<2-hydroxy-3-(2-nitro-1H-imidazol-1-yl)propyl>-1,3-diaminopropane；2-(2-Hydroxy-3-(2-nitroimidazolyl)-propyl)-N,N'-di-t-Boc-1,3-propanediamin；tert-butyl N-[4-hydroxy-2-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]-5-(2-nitroimidazol-1-yl)pentyl]carbamate
• CAS: 159591-78-3
• 化学式: C₁₉H₃₃N₅O₇
• 分子量: 443.5
• InChiKey: UZAUJCRASBDVFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  31
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  161
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(2-hydroxy-3-(2-nitro-1H-imidazol-1-yl)propyl)-N,N'-bis(tert-butyloxycarbonyl)-1,3-propanediamine 在 盐酸 、 氨 、 碳酸氢钠 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 3,3,9,9-tetramethyl-6-(2-hydroxy-3-(2-nitro-1H-imidazol-1-yl)-n-propyl)-4,8-diazaundecane-2,10-dione
  参考文献：
  名称：

  硝基咪唑取代的3,3,9,9-四甲基-4,8-​​二氮杂十一烷-2,10-二酮二肟（丙烯胺肟，PnAOs）的配体：99 99m配合物的配体，可用于低氧组织成像

  摘要：

  一系列2-取代的1,3-二氨基丙烷（1b-1f，1h）已被合成为硝基咪唑取代的3,3,9,9-四甲基-4,8-​​二氮杂癸烷-2,10-二酮二肟的前体（21b，21d，21e和26a-26c）（丙烯胺肟，PnAO）配体。硝基咪唑取代的丙烯胺肟（PnAO）合成所需的3-氯-3-甲基-1-（2-或4-硝基-I H-咪唑-1-基）-2-亚硝基丁烷（18a-e） ）配体由相应的二甲基烯丙基-硝基咪唑（17a-17e）通过加入亚硝酰氯。合成了许多具有静电，疏水或亲水相互作用潜能的硝基咪唑衍生的PnAO配体，作为tech-99m配合物的前体，正在研究中作为低氧的潜在显像剂。用3-氯-3-甲基-1-（2-或4-硝基-1 H-咪唑-1-基）-2-亚硝基丁烷制备在碳原子上取代的PnAO衍生物。使用3-溴-3-甲基丁烷-2-一（24）制备了在中心碳原子上衍生化的三个PnAO 26a-26c。

  DOI：

  10.1016/0040-4020(95)00042-7
• 作为产物：
  描述：

  烯丙基丙二酸二乙酯 在 lithium aluminium tetrahydride 、 氨 、 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 128.0h， 生成 2-(2-hydroxy-3-(2-nitro-1H-imidazol-1-yl)propyl)-N,N'-bis(tert-butyloxycarbonyl)-1,3-propanediamine
  参考文献：
  名称：

  The Synthesis and in vitro Evaluation of a 99mTechnetium-Nitroimidazole Complex Based on a Bis(amine-phenol) Ligand: Comparison to BMS-181321

  摘要：

  We have developed a (99m)Technetium complex for imaging of hypoxic tissue (BMS-181321). Recently, another nitroimidazole derivative, based upon a bis(amine-phenol) ligand, was described in the patent literature. To compare this compound to BMS-181321, we have synthesized the ligand, prepared its Tc-99m complex, and evaluated its performance in two in vitro assays of bioefficacy: membrane permeability and uptake in normoxic and anoxic cardiocytes. In attempting to reproduce the synthesis of the ligand described in the patent application, we found that one intermediate could not be made by the method described, and alternative routes were investigated. Complexation of the bis(amine-phenol) nitroimidazole with Tc-99m gave an apparent single complex; this appeared as a broad peak on HPLC analysis. Purification by a solid-phase method gave a complex with 95% radiochemical purity. This complex was not permeable to cultured bovine brain endothelial cells nor did it show preferential uptake in anoxic myocytes.

  DOI：

  10.1021/jm00050a012

文献信息

• Diagnostic imaging methods using rhenium and technetium complexes
  申请人：Bracco International B.V.

  公开号：US05688487A1

  公开（公告）日：1997-11-18

  Novel methods, processes and metal complexes attached to a hypoxia-localizing moiety comprising a metal, preferably radionuclide of rhenium or technetium; a hypoxia-localizing moiety; and, a complexing ligand, wherein said ligand and said radionuclide combined have cell membrane permeabilities greater than that of sucrose, are disclosed.

  新颖的方法、过程和与缺氧定位基团结合的金属配合物被揭示，所述金属优选为铼或锝的放射性核素；一种缺氧定位基团；以及一种络合配体，其中所述配体和所述放射性核素的结合具有大于蔗糖的细胞膜渗透性。
• The Synthesis and in vitro Evaluation of a 99mTechnetium-Nitroimidazole Complex Based on a Bis(amine-phenol) Ligand: Comparison to BMS-181321
  作者：K. Ramalingam、N. Raju、P. Nanjappan、K. E. Linder、J. Pirro、W. Zeng、W. Rumsey、D. P. Nowotnik、A. D. Nunn

  DOI：10.1021/jm00050a012

  日期：1994.11

  We have developed a (99m)Technetium complex for imaging of hypoxic tissue (BMS-181321). Recently, another nitroimidazole derivative, based upon a bis(amine-phenol) ligand, was described in the patent literature. To compare this compound to BMS-181321, we have synthesized the ligand, prepared its Tc-99m complex, and evaluated its performance in two in vitro assays of bioefficacy: membrane permeability and uptake in normoxic and anoxic cardiocytes. In attempting to reproduce the synthesis of the ligand described in the patent application, we found that one intermediate could not be made by the method described, and alternative routes were investigated. Complexation of the bis(amine-phenol) nitroimidazole with Tc-99m gave an apparent single complex; this appeared as a broad peak on HPLC analysis. Purification by a solid-phase method gave a complex with 95% radiochemical purity. This complex was not permeable to cultured bovine brain endothelial cells nor did it show preferential uptake in anoxic myocytes.
• Synthesis of nitroimidazole substituted 3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioximes (propylene amine oximes, PnAOs): Ligands for technetium-99m complexes with potential for imaging hypoxic tissue
  作者：Kondareddiar Ramalingam、Natarajan Raju、Palaniappa Nanjappan、David P. Nowotnik

  DOI：10.1016/0040-4020(95)00042-7

  日期：1995.3

  synthesized as precursors to nitroimidazole-substituted 3,3,9,9-tetramethyl-4,8-diazaundecane-2,10-dione dioxime (21b, 21d, 21e and 26a-26c) (Propylene Amine Oxime, PnAO) ligands. 3-Chloro-3-methyl-1-(2- or 4-nitro-I H-imidazol-1-yl)-2-nitroso-butanes (18a-e) required for the syntheses of nitroimidazole substituted propylene amine oxime (PnAO) ligands were prepared from the corresponding dimethylallyl-nitroimidazoles

  一系列2-取代的1,3-二氨基丙烷（1b-1f，1h）已被合成为硝基咪唑取代的3,3,9,9-四甲基-4,8-​​二氮杂癸烷-2,10-二酮二肟的前体（21b，21d，21e和26a-26c）（丙烯胺肟，PnAO）配体。硝基咪唑取代的丙烯胺肟（PnAO）合成所需的3-氯-3-甲基-1-（2-或4-硝基-I H-咪唑-1-基）-2-亚硝基丁烷（18a-e） ）配体由相应的二甲基烯丙基-硝基咪唑（17a-17e）通过加入亚硝酰氯。合成了许多具有静电，疏水或亲水相互作用潜能的硝基咪唑衍生的PnAO配体，作为tech-99m配合物的前体，正在研究中作为低氧的潜在显像剂。用3-氯-3-甲基-1-（2-或4-硝基-1 H-咪唑-1-基）-2-亚硝基丁烷制备在碳原子上取代的PnAO衍生物。使用3-溴-3-甲基丁烷-2-一（24）制备了在中心碳原子上衍生化的三个PnAO 26a-26c。