(2R,2'R)-2,2'-(((1,1'-(((oxy-bis(ethane-1,2-diyl))-bis(oxy))-bis(ethane-1,2-diyl))bis(1H-1,2,3-triazole-1,4-diyl))-bis(methylene))-bis(((4-methoxyphenyl)sulfonyl)azanediyl))-bis(N-hydroxy-3-methylbutanamide) | 1378929-07-7

• 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: (2R,2'R)-2,2'-(((1,1'-(((oxy-bis(ethane-1,2-diyl))-bis(oxy))-bis(ethane-1,2-diyl))bis(1H-1,2,3-triazole-1,4-diyl))-bis(methylene))-bis(((4-methoxyphenyl)sulfonyl)azanediyl))-bis(N-hydroxy-3-methylbutanamide)
• 英文别名: (2R)-N-hydroxy-2-[[1-[2-[2-[2-[2-[4-[[[(2R)-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl]-(4-methoxyphenyl)sulfonylamino]methyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]methyl-(4-methoxyphenyl)sulfonylamino]-3-methylbutanamide
• CAS: 1378929-07-7
• 化学式: C₃₈H₅₆N₁₀O₁₃S₂
• 分子量: 925.054
• InChiKey: YWHKQQSHVPCBRN-LQFQNGICSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  63
• 可旋转键数：
  28
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  298
• 氢给体数：
  4
• 氢受体数：
  19

反应信息

• 作为产物：
  描述：

  (R)-tert-butyl 2-(4-methoxyphenylsulfonamido-N-(prop-2-yn-1-yl))-3-methylbutanoate 在 N-甲基吗啉 、 盐酸 、 copper(ll) sulfate pentahydrate 、 1-羟基苯并三唑 、 sodium ascorbate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (R)-2-(N-((1-(2-(2-(2-(2-azidoethoxy)ethoxy)ethoxy)ethyl)-1H-1,2,3-triazol-4-yl)methyl)-4-methoxyphenylsulfonamido)-N-hydroxy-3-methylbutanamide 、 (2R,2'R)-2,2'-(((1,1'-(((oxy-bis(ethane-1,2-diyl))-bis(oxy))-bis(ethane-1,2-diyl))bis(1H-1,2,3-triazole-1,4-diyl))-bis(methylene))-bis(((4-methoxyphenyl)sulfonyl)azanediyl))-bis(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