DFOB-AdAc | 1149568-54-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: DFOB-AdAc
• 英文别名: N-[5-[acetyl(hydroxy)amino]pentyl]-N'-[5-[[4-[5-[[2-(1-adamantyl)acetyl]amino]pentyl-hydroxyamino]-4-oxobutanoyl]amino]pentyl]-N'-hydroxybutanediamide
• CAS: 1149568-54-6
• 化学式: C₃₇H₆₄N₆O₉
• 分子量: 736.95
• InChiKey: PXJFHVILPRXSAD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  52
• 可旋转键数：
  26
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  209
• 氢给体数：
  6
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  甲磺酸去铁敏 、 1-金刚烷乙酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以80%的产率得到DFOB-AdAc
  参考文献：
  名称：

  Conjugates of Desferrioxamine B (DFOB) with Derivatives of Adamantane or with Orally Available Chelators as Potential Agents for Treating Iron Overload

  摘要：

  Desferrioxamine B (DFOB) conjugates with adamantane-1-carboxylic acid, 3-hydroxyadamantane-1-carboxylic acid, 3,5-dimethyladamantane-1-carboxylic acid, adamantane-1-acetic acid, 4-methylphenoxyacetic acid, 3-hydroxy-2-methyl-4-oxo-1-pyridineacetic acid (N-acetic acid derivative of deferiprone), or 4-[3,5-bis(2-hydroxyphenyl)-1,2,4-triazol- 1-yl]benzoic acid (deferasirox) were prepared and the integrity of Fe(III) binding of the compounds was established from electrospray ionization mass spectrometry and RP-HPLC measurements. The extent of intracellular Fe-59 mobilized by the DFOB-3,5-dimethyladamantane-1-carboxylic acid adduct was 3-fold greater than DFOB alone, and the IC50 value of this adduct was 6- or 15-fold greater than DFOB in two different cell types. The relationship between logP and Fe-59 mobilization for the DFOB conjugates showed that maximal mobilization of intracellular Fe-59 Occurred at a logP value similar to 2.3. This parameter, rather than the affinity for Fe(III), appears to influence the extent of intracellular Fe-59 mobilization. The low toxicity-high Fe mobilization efficacy of selected adamantane-based DFOB conjugates underscores the potential of these compounds to treat iron overload disease in patients with transfusional-dependent disorders such as beta-thalassemia.

  DOI：

  10.1021/jm9016703

文献信息

• Conjugates of Desferrioxamine B (DFOB) with Derivatives of Adamantane or with Orally Available Chelators as Potential Agents for Treating Iron Overload
  作者：Joe Liu、Daniel Obando、Liam G. Schipanski、Ludwig K. Groebler、Paul K. Witting、Danuta S. Kalinowski、Des R. Richardson、Rachel Codd

  DOI：10.1021/jm9016703

  日期：2010.2.11

  Desferrioxamine B (DFOB) conjugates with adamantane-1-carboxylic acid, 3-hydroxyadamantane-1-carboxylic acid, 3,5-dimethyladamantane-1-carboxylic acid, adamantane-1-acetic acid, 4-methylphenoxyacetic acid, 3-hydroxy-2-methyl-4-oxo-1-pyridineacetic acid (N-acetic acid derivative of deferiprone), or 4-[3,5-bis(2-hydroxyphenyl)-1,2,4-triazol- 1-yl]benzoic acid (deferasirox) were prepared and the integrity of Fe(III) binding of the compounds was established from electrospray ionization mass spectrometry and RP-HPLC measurements. The extent of intracellular Fe-59 mobilized by the DFOB-3,5-dimethyladamantane-1-carboxylic acid adduct was 3-fold greater than DFOB alone, and the IC50 value of this adduct was 6- or 15-fold greater than DFOB in two different cell types. The relationship between logP and Fe-59 mobilization for the DFOB conjugates showed that maximal mobilization of intracellular Fe-59 Occurred at a logP value similar to 2.3. This parameter, rather than the affinity for Fe(III), appears to influence the extent of intracellular Fe-59 mobilization. The low toxicity-high Fe mobilization efficacy of selected adamantane-based DFOB conjugates underscores the potential of these compounds to treat iron overload disease in patients with transfusional-dependent disorders such as beta-thalassemia.