ferrioxamine B | 82265-75-6

• 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: ferrioxamine B
• 英文别名: ferrioxamine
• CAS: 82265-75-6
• 化学式: C₂₅H₄₅FeN₆O₈*H
• 分子量: 614.523
• InChiKey: SRMBQCVUAVULDJ-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  0.53
• 重原子数：
  40.0
• 可旋转键数：
  23.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  215.95
• 氢给体数：
  3.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  ferrioxamine B 在 高氯酸 、 sodium perchlorate 、 氢气 作用下， 以 水 为溶剂， 生成 铁粉
  参考文献：
  名称：

  Kinetics of stepwise hydrolysis of ferrioxamine B and of formation of diferrioxamine B in acid perchlorate solution

  摘要：

  DOI：

  10.1021/ic00254a009
• 作为产物：
  描述：

  iron(III) chloride 、 甲磺酸去铁敏 以 水 为溶剂， 生成 ferrioxamine B
  参考文献：
  名称：

  Quantifying Intranasally Administered Deferoxamine in Rat Brain Tissue with Mass Spectrometry

  摘要：

  Deferoxamine, a metal chelator, has been shown to be neuroprotective in animal models of ischemic stroke, traumatic brain injury and both subarachnoid and intracerebral hemorrhage. Intranasal deferoxamine (IN DFO) has also shown promise as a potential treatment for multiple neurodegenerative diseases, including Parkinson's and Alzheimer's. However, there have been no attempts to thoroughly understand the dynamics and pharmacokinetics of IN DFO. We developed a new high-performance liquid-chromatography electrospray-tandem mass spectrometry (HPLC/ESI-MS2) method to quantify the combined total levels of DFO, ferrioxamine (FO; DFO bound to iron), and aluminoxamine (AO; aluminum-bound DFO) in brain tissue using a custom-synthesized deuterated analogue (DFO-d(7), Medical Isotopes Inc., Pelham NH) as an internal standard. We applied our method toward understanding the pharmacokinetics of IN DFO delivery to the brain and blood of rats from 15 min to 4 h after delivery. We found that IN delivery successfully targets DFO to the brain to achieve concentrations of 0.5-15 mu M in various brain regions within 15 min, and decreasing though still detectable after 4 h. Systemic exposure was minimized as assessed by concentration in blood serum. Serum concentrations were 0.02 mu M at 15 min and no more than 0.1 mu M at later time points. Compared to blood serum, brain region-specific drug exposure (as measured by area under the curve) ranged from slightly under 10 times exposure in the hippocampus to almost 200 times exposure in the olfactory bulb with IN DFO delivery. These findings represent a major step toward future method development, pharmacokinetic studies, and clinical trials for this promising therapeutic.

  DOI：

  10.1021/acschemneuro.9b00436

文献信息

• Biruš, Mladen; Bradić, Zdravko; Kujundžić, Nikola, Inorganic Chemistry, 1984, vol. 23, # 14, p. 2170 - 2175
  作者：Biruš, Mladen、Bradić, Zdravko、Kujundžić, Nikola、Pribanić, Marijan

  DOI：——

  日期：——
• Quantifying Intranasally Administered Deferoxamine in Rat Brain Tissue with Mass Spectrometry
  作者：Jacob Kosyakovsky、Bruce A. Witthuhn、Aleta L. Svitak、William H. Frey、Leah R. Hanson、Jared M. Fine

  DOI：10.1021/acschemneuro.9b00436

  日期：2019.11.20

  Deferoxamine, a metal chelator, has been shown to be neuroprotective in animal models of ischemic stroke, traumatic brain injury and both subarachnoid and intracerebral hemorrhage. Intranasal deferoxamine (IN DFO) has also shown promise as a potential treatment for multiple neurodegenerative diseases, including Parkinson's and Alzheimer's. However, there have been no attempts to thoroughly understand the dynamics and pharmacokinetics of IN DFO. We developed a new high-performance liquid-chromatography electrospray-tandem mass spectrometry (HPLC/ESI-MS2) method to quantify the combined total levels of DFO, ferrioxamine (FO; DFO bound to iron), and aluminoxamine (AO; aluminum-bound DFO) in brain tissue using a custom-synthesized deuterated analogue (DFO-d(7), Medical Isotopes Inc., Pelham NH) as an internal standard. We applied our method toward understanding the pharmacokinetics of IN DFO delivery to the brain and blood of rats from 15 min to 4 h after delivery. We found that IN delivery successfully targets DFO to the brain to achieve concentrations of 0.5-15 mu M in various brain regions within 15 min, and decreasing though still detectable after 4 h. Systemic exposure was minimized as assessed by concentration in blood serum. Serum concentrations were 0.02 mu M at 15 min and no more than 0.1 mu M at later time points. Compared to blood serum, brain region-specific drug exposure (as measured by area under the curve) ranged from slightly under 10 times exposure in the hippocampus to almost 200 times exposure in the olfactory bulb with IN DFO delivery. These findings represent a major step toward future method development, pharmacokinetic studies, and clinical trials for this promising therapeutic.
• Kinetics of stepwise hydrolysis of ferrioxamine B and of formation of diferrioxamine B in acid perchlorate solution
  作者：Mladen Birus、Zdravko Bradic、Gordana Krznaric、Nikola Kujundzic、Marijan Pribanic、Patricia C. Wilkins、Ralph G. Wilkins

  DOI：10.1021/ic00254a009

  日期：1987.4