diethyl (8-hydroxyquinolin-5-ylmethyl)acetamidomalonate | 686722-47-4

• 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: diethyl (8-hydroxyquinolin-5-ylmethyl)acetamidomalonate
• 英文别名: Diethyl 2-acetamido-2-[(8-hydroxyquinolin-5-yl)methyl]propanedioate
• CAS: 686722-47-4
• 化学式: C₁₉H₂₂N₂O₆
• 分子量: 374.393
• InChiKey: KIXCLLIWPREQRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  diethyl (8-hydroxyquinolin-5-ylmethyl)acetamidomalonate 在 盐酸 、 氯化亚砜 、 α-chymotrypsin 作用下， 以 sodium hydroxide 、 水 为溶剂， 反应 16.0h， 生成 D-3-(8-hydroxyquinolin-5-yl)alanine ethyl ester
  参考文献：
  名称：

  Novel potential neuroprotective agents with both iron chelating and amino acid-based derivatives targeting central nervous system neurons

  摘要：

  Antioxidants and iron chelating molecules are known as neuroprotective agents in animal models of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). In this study, we designed and synthesized a novel bifunctional molecule (M10) with radical scavenging and iron chelating ability on an amino acid carrier likely to be a substrate for system L, thus targeting the compound to the central nervous system (CNS). M10 had a moderate iron affinity in HEPES buffer (pH 7.4) with log K-3 = 12.25 +/- 0.55 but exhibited highly inhibitory action against iron-induced lipid peroxidation, with an IC50 value (12 mu M) comparable to that of desferal (DFO). EPR studies indicated that M10 was a highly potent (center dot)0H scavenger with an IC50 of about 0.3 molar ratio of M10 to H2O2. In PC12 cell culture, M10 was at least as potent as the anti-Parkinson drug rasagiline in protecting against cell death induced by serum-deprivation and by 6-hydroxydopamine (6-OHDA). These results suggest that M10 deserves further investigation as a potential agent for the treatment of neurodegenerative disorders such as AD and PD. (c) 2005 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2005.09.003
• 作为产物：
  描述：

  8-羟基喹啉 在 吡啶 、 盐酸 、 sodium 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 diethyl (8-hydroxyquinolin-5-ylmethyl)acetamidomalonate
  参考文献：
  名称：

  Novel potential neuroprotective agents with both iron chelating and amino acid-based derivatives targeting central nervous system neurons

  摘要：

  Antioxidants and iron chelating molecules are known as neuroprotective agents in animal models of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). In this study, we designed and synthesized a novel bifunctional molecule (M10) with radical scavenging and iron chelating ability on an amino acid carrier likely to be a substrate for system L, thus targeting the compound to the central nervous system (CNS). M10 had a moderate iron affinity in HEPES buffer (pH 7.4) with log K-3 = 12.25 +/- 0.55 but exhibited highly inhibitory action against iron-induced lipid peroxidation, with an IC50 value (12 mu M) comparable to that of desferal (DFO). EPR studies indicated that M10 was a highly potent (center dot)0H scavenger with an IC50 of about 0.3 molar ratio of M10 to H2O2. In PC12 cell culture, M10 was at least as potent as the anti-Parkinson drug rasagiline in protecting against cell death induced by serum-deprivation and by 6-hydroxydopamine (6-OHDA). These results suggest that M10 deserves further investigation as a potential agent for the treatment of neurodegenerative disorders such as AD and PD. (c) 2005 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2005.09.003

文献信息

• Neuroprotective iron chelators and pharmaceutical compositions comprising them
  申请人：Youdim Moussa

  公开号：US20060234927A1

  公开（公告）日：2006-10-19

  Novel iron chelators exhibiting neuroprotective and good transport properties are useful in iron chelation therapy for treatment of a disease, disorder or condition associated with iron overload and oxidative stress, eg. a neurodegenerative or cerebrovascular disease or disorder, a neoplastic disease, hemochromatosis, thalassemia, a cardiovascular disease, diabetes, a inflammatory disorder, anthracycline cardiotoxicity, a viral infection, a protozoal infection, a yeast infection, retarding ageing, and prevention and/or treatment of skin ageing and skin protection against sunlight and/or UV light. The iron chelator function is provided by a 8-hydroxyquinoline, a hydroxypyridinone or a hydroxamate moiety, the neuroprotective function is imparted to the compound e.g. by a neuroprotective peptide, and a combined antiapoptotic and neuroprotective function by a propargyl group.

  表现出神经保护和良好转运特性的新型铁螯合剂，在治疗与铁过载和氧化应激相关的疾病、障碍或病况中非常有用，例如神经退行性或脑血管疾病或障碍、肿瘤性疾病、血色病、地中海贫血、心血管疾病、糖尿病、炎症性疾病、蒽环类心肌毒性、病毒感染、原虫感染、酵母感染、延缓衰老，以及预防和/或治疗皮肤衰老和皮肤对阳光和/或紫外线的保护。铁螯合剂功能由8-羟基喹啉、羟基吡啶酮或羟肟基团提供，神经保护功能由神经保护肽赋予化合物，而丙炔基则提供了联合抗凋亡和神经保护功能。
• NEUROPROTECTIVE IRON CHELATORS AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM
  申请人：YOUDIM MOUSSA

  公开号：US20120058945A1

  公开（公告）日：2012-03-08

  Novel iron chelators exhibiting neuroprotective and good transport properties are useful in iron chelation therapy for treatment of a disease, disorder or condition associated with iron overload and oxidative stress, e.g., a neurodegenerative or cerebrovascular disease or disorder, a neoplastic disease, hemochromatosis, thalassemia, a cardiovascular disease, diabetes, an inflammatory disorder, anthracycline cardiotoxicity, a viral infection, a protozoal infection, a yeast infection, retarding aging, and prevention and/or treatment of skin aging and skin protection against sunlight and/or UV light. The iron chelator function is provided by a 8-hydroxyquinoline, a hydroxypyridinone or a hydroxamate moiety. The neuroprotective function is imparted to the compound, e.g., by a neuroprotective peptide. A combined antiapoptotic and neuroprotective function is provided by a propargyl group.

  表现出神经保护和良好输送特性的新型铁螯合剂，可用于治疗与铁过载和氧化应激相关的疾病、障碍或病况，例如神经退行性或脑血管疾病或障碍、肿瘤性疾病、血色病、地中海贫血、心血管疾病、糖尿病、炎症性疾病、蒽环类心肌毒性、病毒感染、原虫感染、酵母感染、延缓衰老以及预防和/或治疗皮肤老化和皮肤对阳光和/或紫外线的保护。铁螯合剂功能由8-羟基喹啉、羟基吡啶酮或羟肟酸基团提供。神经保护功能由神经保护肽等化合物赋予。丙炔基提供了联合抗凋亡和神经保护功能。
• US8058442B2
  申请人：——

  公开号：US8058442B2

  公开（公告）日：2011-11-15
• Novel potential neuroprotective agents with both iron chelating and amino acid-based derivatives targeting central nervous system neurons
  作者：Hailin Zheng、Moussa B.H. Youdim、Lev M. Weiner、Mati Fridkin

  DOI：10.1016/j.bcp.2005.09.003

  日期：2005.11

  Antioxidants and iron chelating molecules are known as neuroprotective agents in animal models of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). In this study, we designed and synthesized a novel bifunctional molecule (M10) with radical scavenging and iron chelating ability on an amino acid carrier likely to be a substrate for system L, thus targeting the compound to the central nervous system (CNS). M10 had a moderate iron affinity in HEPES buffer (pH 7.4) with log K-3 = 12.25 +/- 0.55 but exhibited highly inhibitory action against iron-induced lipid peroxidation, with an IC50 value (12 mu M) comparable to that of desferal (DFO). EPR studies indicated that M10 was a highly potent (center dot)0H scavenger with an IC50 of about 0.3 molar ratio of M10 to H2O2. In PC12 cell culture, M10 was at least as potent as the anti-Parkinson drug rasagiline in protecting against cell death induced by serum-deprivation and by 6-hydroxydopamine (6-OHDA). These results suggest that M10 deserves further investigation as a potential agent for the treatment of neurodegenerative disorders such as AD and PD. (c) 2005 Elsevier Inc. All rights reserved.