N,N'-(2-nitrobenzenesulfonamide)-N,N'-[6-((methoxycarbonyl)pyridin-2-yl)methyl]-1,2-diaminoethane | 1450624-92-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N,N'-(2-nitrobenzenesulfonamide)-N,N'-[6-((methoxycarbonyl)pyridin-2-yl)methyl]-1,2-diaminoethane
• 英文别名: Methyl 6-[[2-[(6-methoxycarbonylpyridin-2-yl)methyl-(2-nitrophenyl)sulfonylamino]ethyl-(2-nitrophenyl)sulfonylamino]methyl]pyridine-2-carboxylate；methyl 6-[[2-[(6-methoxycarbonylpyridin-2-yl)methyl-(2-nitrophenyl)sulfonylamino]ethyl-(2-nitrophenyl)sulfonylamino]methyl]pyridine-2-carboxylate
• CAS: 1450624-92-6
• 化学式: C₃₀H₂₈N₆O₁₂S₂
• 分子量: 728.717
• InChiKey: SKYULSPLLYJYPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  50
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  262
• 氢给体数：
  0
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  N,N'-(2-nitrobenzenesulfonamide)-N,N'-[6-((methoxycarbonyl)pyridin-2-yl)methyl]-1,2-diaminoethane 在 potassium carbonate 、 苯硫酚 作用下， 以 四氢呋喃 为溶剂， 反应 72.0h， 生成 1,2-[{6-(methoxycarbonyl)pyridin-2-yl}methylamino]ethane
  参考文献：
  名称：

  H₄octapa-Trastuzumab: Versatile Acyclic Chelate System for ¹¹¹In and ¹⁷⁷Lu Imaging and Therapy

  摘要：

  A bifunctional derivative of the versatile acyclic chelator H(4)octapa, p-SCN-Bn-H(4)octapa, has been synthesized for the first time. The chelator was conjugated to the HER2/neutargeting antibody trastuzumab and labeled in high radiochemical purity and specific activity with the radioisotopes In-111 and Lu-177. The in vivo behavior of the resulting radio-immunoconjugates was investigated in mice bearing ovarian cancer xenografts and compared to analogous radioimmuno-conjugates employing the ubiquitous chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). The H(4)octapa-trastuzumab conjugates displayed faster radiolabeling kinetics with more reproducible yields under milder conditions (15 min, RT, similar to 94-95%) than those based on DOTA-trastuzumab (60 min, 37 degrees C, similar to 50-88%). Further, antibody integrity was better preserved in the In-111- and Lu-177-octapa-trastuzumab constructs, with immunoreactive fractions of 0.99 for each compared to 0.93-0.95 for In-111- and Lu-177-DOTA-trastuzumab. These results translated to improved in vivo biodistribution profiles and SPECT imaging results for In-111- and Lu-177-octapa-trastuzumab compared to In-111- and Lu-177-DOTA-trastuzumab, with increased tumor uptake and higher tumor-to-tissue activity ratios.

  DOI：

  10.1021/ja4049493
• 作为产物：
  描述：

  邻硝基苯磺酰氯 在 碳酸氢钠 、 sodium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成 N,N'-(2-nitrobenzenesulfonamide)-N,N'-[6-((methoxycarbonyl)pyridin-2-yl)methyl]-1,2-diaminoethane
  参考文献：
  名称：

  H₄octapa-Trastuzumab: Versatile Acyclic Chelate System for ¹¹¹In and ¹⁷⁷Lu Imaging and Therapy

  摘要：

  A bifunctional derivative of the versatile acyclic chelator H(4)octapa, p-SCN-Bn-H(4)octapa, has been synthesized for the first time. The chelator was conjugated to the HER2/neutargeting antibody trastuzumab and labeled in high radiochemical purity and specific activity with the radioisotopes In-111 and Lu-177. The in vivo behavior of the resulting radio-immunoconjugates was investigated in mice bearing ovarian cancer xenografts and compared to analogous radioimmuno-conjugates employing the ubiquitous chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). The H(4)octapa-trastuzumab conjugates displayed faster radiolabeling kinetics with more reproducible yields under milder conditions (15 min, RT, similar to 94-95%) than those based on DOTA-trastuzumab (60 min, 37 degrees C, similar to 50-88%). Further, antibody integrity was better preserved in the In-111- and Lu-177-octapa-trastuzumab constructs, with immunoreactive fractions of 0.99 for each compared to 0.93-0.95 for In-111- and Lu-177-DOTA-trastuzumab. These results translated to improved in vivo biodistribution profiles and SPECT imaging results for In-111- and Lu-177-octapa-trastuzumab compared to In-111- and Lu-177-DOTA-trastuzumab, with increased tumor uptake and higher tumor-to-tissue activity ratios.

  DOI：

  10.1021/ja4049493

文献信息

• H₄octapa-Trastuzumab: Versatile Acyclic Chelate System for ¹¹¹In and ¹⁷⁷Lu Imaging and Therapy
  作者：Eric W. Price、Brian M. Zeglis、Jacqueline F. Cawthray、Caterina F. Ramogida、Nicholas Ramos、Jason S. Lewis、Michael J. Adam、Chris Orvig

  DOI：10.1021/ja4049493

  日期：2013.8.28

  A bifunctional derivative of the versatile acyclic chelator H(4)octapa, p-SCN-Bn-H(4)octapa, has been synthesized for the first time. The chelator was conjugated to the HER2/neutargeting antibody trastuzumab and labeled in high radiochemical purity and specific activity with the radioisotopes In-111 and Lu-177. The in vivo behavior of the resulting radio-immunoconjugates was investigated in mice bearing ovarian cancer xenografts and compared to analogous radioimmuno-conjugates employing the ubiquitous chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). The H(4)octapa-trastuzumab conjugates displayed faster radiolabeling kinetics with more reproducible yields under milder conditions (15 min, RT, similar to 94-95%) than those based on DOTA-trastuzumab (60 min, 37 degrees C, similar to 50-88%). Further, antibody integrity was better preserved in the In-111- and Lu-177-octapa-trastuzumab constructs, with immunoreactive fractions of 0.99 for each compared to 0.93-0.95 for In-111- and Lu-177-DOTA-trastuzumab. These results translated to improved in vivo biodistribution profiles and SPECT imaging results for In-111- and Lu-177-octapa-trastuzumab compared to In-111- and Lu-177-DOTA-trastuzumab, with increased tumor uptake and higher tumor-to-tissue activity ratios.