1-[4-(6,7-Dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]-3-(4-fluorophenyl)urea | 1033263-75-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[4-(6,7-Dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]-3-(4-fluorophenyl)urea
• CAS: 1033263-75-0
• 化学式: C₂₄H₁₉F₂N₃O₄
• 分子量: 451.429
• InChiKey: DNLCCAYVZKRIEN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  81.7
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-[4-(6,7-Dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]-3-(4-fluorophenyl)urea 、 异丙烯基氯甲酸酯 在 N-甲基吗啉 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以74%的产率得到[4-(6,7-dimethoxy-quinolin-4-yloxy)-3-fluorophenyl]-carbamic acid isopropenyl ester
  参考文献：
  名称：

  Formation of fluorine-18 labeled diaryl ureas—labeled VEGFR-2/PDGFR dual inhibitors as molecular imaging agents for angiogenesis

  摘要：

  Urea subunits are common components of various pharmaceuticals' core structure. Since in most cases the design and development of PET biomarkers is based on approved or potential drugs, there is a growing need for a general labeling methodology of urea-containing pharmacophores. As a part of research in the field of molecular imaging of angiogenic processes, we synthesized several highly potent VEGFR-2/PDGFR dual inhibitors as potential PET biomarkers. The structure of these inhibitors is based on the N-phenyl-N'-{4-(4-quinolyloxy)phenyl} urea skeleton. A representative inhibitor was successfully labeled with fluorine-18 by a three-step process. Initially, a two-step radiosynthesis of 4-[F-18]fluoro-aniline from 1,4- dinitrobenzene (60 min, EOB decay corrected yield: 63%) was performed. At the third and final step, the 4-[F-18]fluoro-aniline synthon reacted for 30 min at room temperature with 4-(2-fluoro-4-isocyanato-phenoxy)-6,7-dimethoxy-quinoline to give complete conversion of the labeled synthon to 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluoro-phenyl]-3-(4-[F-18]fluoro-phenyl)-urea.The desired labeled product was obtained after total radiosynthesis time of 3 h including HPLC purification with 46 +/- 1% EOB decay corrected radiochemical yield, 99% radiochemical purity, 99% chemical purity, and a specific activity of 400 +/- 37 GBq/mmol (n = 5). (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.02.081
• 作为产物：
  描述：

  三光气 、 4-氟苯胺 、 4-[(6,7-dimethoxyquinolin-4-yl)oxy]-3-fluoroaniline 在 三光气 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以50%的产率得到1-[4-(6,7-Dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]-3-(4-fluorophenyl)urea
  参考文献：
  名称：

  Formation of fluorine-18 labeled diaryl ureas—labeled VEGFR-2/PDGFR dual inhibitors as molecular imaging agents for angiogenesis

  摘要：

  Urea subunits are common components of various pharmaceuticals' core structure. Since in most cases the design and development of PET biomarkers is based on approved or potential drugs, there is a growing need for a general labeling methodology of urea-containing pharmacophores. As a part of research in the field of molecular imaging of angiogenic processes, we synthesized several highly potent VEGFR-2/PDGFR dual inhibitors as potential PET biomarkers. The structure of these inhibitors is based on the N-phenyl-N'-{4-(4-quinolyloxy)phenyl} urea skeleton. A representative inhibitor was successfully labeled with fluorine-18 by a three-step process. Initially, a two-step radiosynthesis of 4-[F-18]fluoro-aniline from 1,4- dinitrobenzene (60 min, EOB decay corrected yield: 63%) was performed. At the third and final step, the 4-[F-18]fluoro-aniline synthon reacted for 30 min at room temperature with 4-(2-fluoro-4-isocyanato-phenoxy)-6,7-dimethoxy-quinoline to give complete conversion of the labeled synthon to 1-[4-(6,7-dimethoxyquinolin-4-yloxy)-3-fluoro-phenyl]-3-(4-[F-18]fluoro-phenyl)-urea.The desired labeled product was obtained after total radiosynthesis time of 3 h including HPLC purification with 46 +/- 1% EOB decay corrected radiochemical yield, 99% radiochemical purity, 99% chemical purity, and a specific activity of 400 +/- 37 GBq/mmol (n = 5). (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.02.081