methyl (2S,4R)-4-((E)-3-(4-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethoxy)-3-methoxyphenyl)acrylamido)-1-(3,4,5-trimethoxybenzoyl)pyrrolidine-2-carboxylate | 1271743-37-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (2S,4R)-4-((E)-3-(4-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethoxy)-3-methoxyphenyl)acrylamido)-1-(3,4,5-trimethoxybenzoyl)pyrrolidine-2-carboxylate
• CAS: 1271743-37-3
• 化学式: C₃₄H₄₇N₃O₁₂
• 分子量: 689.76
• InChiKey: XOPRQLJHTSYGBH-QAQFROJPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.69
• 重原子数：
  49.0
• 可旋转键数：
  21.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  175.57
• 氢给体数：
  2.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  methyl (2S,4R)-4-((E)-3-(4-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethoxy)-3-methoxyphenyl)acrylamido)-1-(3,4,5-trimethoxybenzoyl)pyrrolidine-2-carboxylate 在 盐酸羟胺 、 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以59%的产率得到(2S,4R)-4-[[(E)-3-[4-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethoxy]-3-methoxyphenyl]prop-2-enoyl]amino]-N-hydroxy-1-(3,4,5-trimethoxybenzoyl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Design and Synthesis of Small-Molecule Fluorescent Photoprobes Targeted to Aminopeptdase N (APN/CD13) for Optical Imaging of Angiogenesis

  摘要：

  We report here the synthesis of a nonpeptide, small-molecule fluorescent imaging agent with high affinity to aminopeptidase N (APN/CD13), a key player in a variety of pathophysiological angiogenic processes. On the basis of a recently described lead structure, we synthesized three putative precursor compounds by introducing polyethylene glycol (PEG) spacers comprising amino groups for dye labeling. Different attachment sites resulted in substantial differences in target affinity, cell toxicity, and target imaging performance. In comparison to bestatin, a natural inhibitor of many aminopeptidases, two of our compounds (22, 23) exhibit comparable inhibition potency, while a third (21) does not show any inhibiting effect. Cell binding assays with APN-positive BT-549 and APN-negative BT-20 cells and the final fluorescent probes Cy 5.5-21 and Cy 5.5-23 confirm these findings. The favorable characteristics of Cy 5.5-23 will now be proven in in vivo experiments with murine models of high APN expression and may serve as a tool to better understand APN pathophysiology.

  DOI：

  10.1021/bc400074w
• 作为产物：
  描述：

  N-Boc-反式-4-氨基-L-脯氨酸甲酯盐酸盐 在 TBTU 、 水 、 1-羟基苯并三唑 、 三乙胺 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 71.5h， 生成 methyl (2S,4R)-4-((E)-3-(4-(2-(2-(2-(2-aminoethoxy)ethoxy)ethoxy)ethoxy)-3-methoxyphenyl)acrylamido)-1-(3,4,5-trimethoxybenzoyl)pyrrolidine-2-carboxylate
  参考文献：
  名称：

  Design and Synthesis of Small-Molecule Fluorescent Photoprobes Targeted to Aminopeptdase N (APN/CD13) for Optical Imaging of Angiogenesis

  摘要：

  We report here the synthesis of a nonpeptide, small-molecule fluorescent imaging agent with high affinity to aminopeptidase N (APN/CD13), a key player in a variety of pathophysiological angiogenic processes. On the basis of a recently described lead structure, we synthesized three putative precursor compounds by introducing polyethylene glycol (PEG) spacers comprising amino groups for dye labeling. Different attachment sites resulted in substantial differences in target affinity, cell toxicity, and target imaging performance. In comparison to bestatin, a natural inhibitor of many aminopeptidases, two of our compounds (22, 23) exhibit comparable inhibition potency, while a third (21) does not show any inhibiting effect. Cell binding assays with APN-positive BT-549 and APN-negative BT-20 cells and the final fluorescent probes Cy 5.5-21 and Cy 5.5-23 confirm these findings. The favorable characteristics of Cy 5.5-23 will now be proven in in vivo experiments with murine models of high APN expression and may serve as a tool to better understand APN pathophysiology.

  DOI：

  10.1021/bc400074w