(R)-2-(N-(4-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethoxy)benzyl)-4-methoxyphenylsulfonamido)-N-hydroxy-3-methylbutanamide | 1151451-90-9

• 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: (R)-2-(N-(4-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethoxy)benzyl)-4-methoxyphenylsulfonamido)-N-hydroxy-3-methylbutanamide
• CAS: 1151451-90-9
• 化学式: C₂₇H₃₉N₅O₉S
• 分子量: 609.701
• InChiKey: RRNRJMKOJVEKQF-AREMUKBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.16
• 重原子数：
  42.0
• 可旋转键数：
  21.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  181.62
• 氢给体数：
  2.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  1-fluoro-3,6,9,12,15-pentaoxaoctadec-17-yne 、 (R)-2-(N-(4-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethoxy)benzyl)-4-methoxyphenylsulfonamido)-N-hydroxy-3-methylbutanamide 在 copper(ll) sulfate pentahydrate 、 sodium ascorbate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以6%的产率得到(R)-2-(N-(4-(2-(2-(2-(2-(4-(16-fluoro-2,5,8,11,14-pentaoxahexadecyl)-1H-1,2,3-triazol-1-yl)ethoxy)ethoxy)ethoxy)ethoxy)benzyl)-4-methoxyphenylsulfonamido)-N-hydroxy-3-methylbutanamide
  参考文献：
  名称：

  A New Class of Highly Potent Matrix Metalloproteinase Inhibitors Based on Triazole-Substituted Hydroxamates: (Radio)Synthesis and in Vitro and First in Vivo Evaluation

  摘要：

  In vivo imaging of MMPs is of great (pre)clinical interest and can potentially be realized with modern three-dimensional and noninvasive in vivo molecular imaging techniques such as positron emission tomography (PET). Consequently, MMP inhibitors (MMPIs) radiolabeled with positron emitting nuclides (e.g., F-18) represent a suitable tool for the visualization of activated MMPs with PET. On the basis of our previous work and results regarding radiolabeled and unlabeled derivatives of the nonselective MMPIs, we discovered a new class of fluorinated MMPIs with a triazole-substituted hydroxamate substructure. These novel MMPIs are characterized by an increased hydrophilicity compared with the lead structures and excellent MMP inhibition potencies for MMP-2, MMP-8, MMP-9, and MMP-13 (IC50 = 0.006-107 nM). Therefore, one promising fluorinated triazole-substituted hydroxamate (30b) was selected and resynthesised as its F-18-labeled version to yield the potential PET radioligand [F-18]30b. The biodistribution behavior of this novel compound was investigated with small animal PET.

  DOI：

  10.1021/jm300199g
• 作为产物：
  描述：

  (R)-2-(N-(4-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethoxy)benzyl)-4-methoxyphenylsulfonamido)-3-methylbutanoic acid 在 N-甲基吗啉 、 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.5h， 生成 (R)-2-(N-(4-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethoxy)benzyl)-4-methoxyphenylsulfonamido)-N-hydroxy-3-methylbutanamide
  参考文献：
  名称：

  A New Class of Highly Potent Matrix Metalloproteinase Inhibitors Based on Triazole-Substituted Hydroxamates: (Radio)Synthesis and in Vitro and First in Vivo Evaluation

  摘要：

  In vivo imaging of MMPs is of great (pre)clinical interest and can potentially be realized with modern three-dimensional and noninvasive in vivo molecular imaging techniques such as positron emission tomography (PET). Consequently, MMP inhibitors (MMPIs) radiolabeled with positron emitting nuclides (e.g., F-18) represent a suitable tool for the visualization of activated MMPs with PET. On the basis of our previous work and results regarding radiolabeled and unlabeled derivatives of the nonselective MMPIs, we discovered a new class of fluorinated MMPIs with a triazole-substituted hydroxamate substructure. These novel MMPIs are characterized by an increased hydrophilicity compared with the lead structures and excellent MMP inhibition potencies for MMP-2, MMP-8, MMP-9, and MMP-13 (IC50 = 0.006-107 nM). Therefore, one promising fluorinated triazole-substituted hydroxamate (30b) was selected and resynthesised as its F-18-labeled version to yield the potential PET radioligand [F-18]30b. The biodistribution behavior of this novel compound was investigated with small animal PET.

  DOI：

  10.1021/jm300199g