valerylamide deferoxamine | 103991-47-5

• 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: valerylamide deferoxamine
• 英文别名: N-Valeryl-desferrioxamin B；N-Pentanoyl-deferoxamine；N-[5-[acetyl(hydroxy)amino]pentyl]-N'-hydroxy-N'-[5-[[4-[hydroxy-[5-(pentanoylamino)pentyl]amino]-4-oxobutanoyl]amino]pentyl]butanediamide
• CAS: 103991-47-5
• 化学式: C₃₀H₅₆N₆O₉
• 分子量: 644.809
• InChiKey: HBQSHRDHPUFMLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  45
• 可旋转键数：
  27
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 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：

  去铁胺 、 戊酰氯 以 氯仿 为溶剂， 反应 0.5h， 生成 valerylamide deferoxamine
  参考文献：
  名称：

  Synthesis and Solution Properties of Deferoxamine Amides

  摘要：

  The poor membrane permeability and oral bioavailability of the iron chelating agent deferoxamine (DFO) mesylate result from the low octanol/water partition coefficient and high aqueous solubility. With the ultimate aim to improve biomembrane permeability while retaining the iron-binding ability of DFO, a series of more lipophilic amides were prepared by reacting the terminal primary amino group with fatty and aromatic acid chlorides or anhydrides. Octanol/water partition coefficients and equilibrium solubilities of these analogs in solvents, chosen to delineate physicochemical interactions, were determined as a function of temperature. Solid-state properties were evaluated by calorimetry. All DFO amide derivatives had higher melting points, indicating that derivatives formed strong intermolecular interactions in the solid phase. Formamidation of the primary amine of deferoxamine resulted in a 200-fold increase in the octanol/water partition coefficient and reduced aqueous solubility at least 2000-fold compared with the parent molecule. The partition coefficient increased and aqueous solubility decreased 2-fold with the addition of each methylene group in the homologous series of aliphatic amides. Solubilities of the derivatives in water-saturated octanol and hexane showed irregular profiles as a function of increasing aliphatic chain length that were attributed to intermolecular packing in the solid state. The temperature dependence of the partition coefficients was interpreted to indicate that interfacial transfer of the deferoxamine amides was, in part, affected by an apparent diminished ability to form energetically favorable interactions in the water-saturated organic phase.

  DOI：

  10.1002/1520-6017(200012)89:12<1525::aid-jps3>3.0.co;2-t

文献信息

• Stoffwechselprodukte von Mikroorganismen. 43. Mitteilung. Zur Kenntnis von Desferrioxamin B
  作者：H. Bickel、H. Keberle、E. Vischer

  DOI：10.1002/hlca.19630460433

  日期：——

  Chemical and physical properties of desferrioxamin B, the iron free ground substance of ferrioxamin B, are described.

  描述了铁氧还蛋白B（铁氧还蛋白B的无铁研磨物质）的化学和物理性质。
• Synthesis and Solution Properties of Deferoxamine Amides
  作者：Peter M. Ihnat、Jonathan L. Vennerstrom、Dennis H. Robinson

  DOI：10.1002/1520-6017(200012)89:12<1525::aid-jps3>3.0.co;2-t

  日期：2000.12

  The poor membrane permeability and oral bioavailability of the iron chelating agent deferoxamine (DFO) mesylate result from the low octanol/water partition coefficient and high aqueous solubility. With the ultimate aim to improve biomembrane permeability while retaining the iron-binding ability of DFO, a series of more lipophilic amides were prepared by reacting the terminal primary amino group with fatty and aromatic acid chlorides or anhydrides. Octanol/water partition coefficients and equilibrium solubilities of these analogs in solvents, chosen to delineate physicochemical interactions, were determined as a function of temperature. Solid-state properties were evaluated by calorimetry. All DFO amide derivatives had higher melting points, indicating that derivatives formed strong intermolecular interactions in the solid phase. Formamidation of the primary amine of deferoxamine resulted in a 200-fold increase in the octanol/water partition coefficient and reduced aqueous solubility at least 2000-fold compared with the parent molecule. The partition coefficient increased and aqueous solubility decreased 2-fold with the addition of each methylene group in the homologous series of aliphatic amides. Solubilities of the derivatives in water-saturated octanol and hexane showed irregular profiles as a function of increasing aliphatic chain length that were attributed to intermolecular packing in the solid state. The temperature dependence of the partition coefficients was interpreted to indicate that interfacial transfer of the deferoxamine amides was, in part, affected by an apparent diminished ability to form energetically favorable interactions in the water-saturated organic phase.