DFOB-AdAdMe | 1149568-52-4

• 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-AdAdMe
• 英文别名: N-[5-[acetyl(hydroxy)amino]pentyl]-N'-[5-[[4-[5-[(3,5-dimethyladamantane-1-carbonyl)amino]pentyl-hydroxyamino]-4-oxobutanoyl]amino]pentyl]-N'-hydroxybutanediamide
• CAS: 1149568-52-4
• 化学式: C₃₈H₆₆N₆O₉
• 分子量: 750.977
• InChiKey: MFAUREOOURUGSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  53
• 可旋转键数：
  25
• 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

• 作为反应物：
  描述：

  iron(III) chloride hexahydrate 、 DFOB-AdAdMe 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  去铁胺B（DFOB）的金刚烷基和其他基于多环笼的缀合物，用于治疗帕金森氏病细胞模型中铁介导的毒性。

  摘要：

  多巴胺能神经元的死亡是帕金森氏病（PD）的主要病理标志。PD脑黑质内的铁被认为可通过羟基自由基引起的氧化损伤来催化这种神经元死亡。去除这种过量的铁代表了PD的潜在治疗策略。通过金刚烷基-（1-4，8-12），解构的金刚烷基单元（5-7），降冰片（e）ne-（13- 16）或末端胺基的双环[2.2.2]辛烷基（17）辅助片段。实验logP值的范围为1-17（logP = 0.15-2.82）大于水溶性DFOB（logP -2.29），疏水性增加，旨在改善细胞膜的转运，促进细胞内铁的螯合。首次活性筛选显示，具有甲基取代的金刚烷基（1-3），去甲金刚烷基（5）或1-戊基双环[2.2.2]辛烷（17）辅助基团的化合物可在与PD相关的汇合性SK中显着缓解铁介导的氧化应激-N-BE2-M17神经母细胞瘤细胞（M17细胞）暴露于1,1'-二甲基-4,4'-联吡啶鎓（百草枯，PQ）或H2O2。在对PQ处理

  DOI：

  10.1016/j.bmcl.2017.03.001
• 作为产物：
  描述：

  3,5-二甲基金刚烷-1-羧酸 、 甲磺酸去铁敏 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-AdAdMe
  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

• [EN] NON-TOXIC IRON CHELATORS WITH NEUROPROTECTIVE POTENTIAL<br/>[FR] CHÉLATEURS DE FER NON TOXIQUES À POTENTIEL NEUROPROTECTEUR
  申请人：UNIV SYDNEY

  公开号：WO2017201581A1

  公开（公告）日：2017-11-30

  The present invention relates to new desferrioxamine B-based compounds that may be useful to treat neurodegenerative diseases, to their preparation, and to compositions including the compounds. The present invention also relates to the use of the compounds, as well as compositions including the compounds, in the treatment of neurodegenerative disorders (such as Parkinson's disease).

  本发明涉及一种基于新的去铁胺B的化合物，可能有用于治疗神经退行性疾病，以及其制备和包括该化合物的组合物。本发明还涉及使用该化合物以及包括该化合物的组合物治疗神经退行性疾病（如帕金森病）。
• US8309583B2
  申请人：——

  公开号：US8309583B2

  公开（公告）日：2012-11-13
• Adamantyl- and other polycyclic cage-based conjugates of desferrioxamine B (DFOB) for treating iron-mediated toxicity in cell models of Parkinson’s disease
  作者：Thomas J. Telfer、Jeffrey R. Liddell、Clare Duncan、Anthony R. White、Rachel Codd

  DOI：10.1016/j.bmcl.2017.03.001

  日期：2017.4

  facilitate intracellular iron sequestration. The first activity screen showed compounds with methyl-substituted adamantyl (1-3), noradamantyl (5), or 1-pentylbicyclo[2.2.2]octane (17) ancillary groups significantly rescued iron-mediated oxidative stress in confluent PD-relevant SK-N-BE2-M17 neuroblastoma cells (M17 cells) exposed to 1,1'-dimethyl-4,4'-bipyridinium (paraquat, PQ) or H2O2. The second dose-dependence

  多巴胺能神经元的死亡是帕金森氏病（PD）的主要病理标志。PD脑黑质内的铁被认为可通过羟基自由基引起的氧化损伤来催化这种神经元死亡。去除这种过量的铁代表了PD的潜在治疗策略。通过金刚烷基-（1-4，8-12），解构的金刚烷基单元（5-7），降冰片（e）ne-（13- 16）或末端胺基的双环[2.2.2]辛烷基（17）辅助片段。实验logP值的范围为1-17（logP = 0.15-2.82）大于水溶性DFOB（logP -2.29），疏水性增加，旨在改善细胞膜的转运，促进细胞内铁的螯合。首次活性筛选显示，具有甲基取代的金刚烷基（1-3），去甲金刚烷基（5）或1-戊基双环[2.2.2]辛烷（17）辅助基团的化合物可在与PD相关的汇合性SK中显着缓解铁介导的氧化应激-N-BE2-M17神经母细胞瘤细胞（M17细胞）暴露于1,1'-二甲基-4,4'-联吡啶鎓（百草枯，PQ）或H2O2。在对PQ处理
• 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.