2-amino-3-(8-hydroxyquinolin-5-yl)propanoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-amino-3-(8-hydroxyquinolin-5-yl)propanoic acid
• 英文别名: 3-(8-Hydroxyquinolin-5-yl)alanine；(2S)-2-amino-3-(8-hydroxyquinolin-5-yl)propanoic acid
• 化学式: C₁₂H₁₂N₂O₃
• 分子量: 232.239
• InChiKey: LCHDHNGXRBTPLK-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  96.4
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-3-(8-hydroxyquinolin-5-yl)propanoic acid 、 氯化亚砜 、 乙醇 在 无水氯化钙 、 乙醇 、 DCM MeOH AcOH 作用下， 以 氮气 为溶剂， 反应 17.0h， 生成 3-(8-Hydroxyquinolin-5-yl)alanine ethyl ester
  参考文献：
  名称：

  Neuroprotective iron chelators and pharmaceutical compositions comprising them

  摘要：

  具有神经保护和良好运输特性的新型铁螯合剂在铁螯合疗法中用于治疗与铁过载和氧化应激相关的疾病、失调或病况，例如神经退行性或脑血管疾病或失调、恶性肿瘤、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/或治疗皮肤老化和保护皮肤免受阳光和/或紫外线的损伤。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，而丙炔基则提供了一种联合的抗凋亡和神经保护功能。

  公开号：

  US08058442B2
• 作为产物：
  描述：

  DL-3-(8-hydroxyquinolin-5-yl)alanine 在 氯化亚砜 、 α-chymotrypsin 作用下， 以 sodium hydroxide 、 水 为溶剂， 反应 6.0h， 生成 2-amino-3-(8-hydroxyquinolin-5-yl)propanoic acid
  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

• Significant Expansion of the Fluorescent Protein Chromophore through the Genetic Incorporation of a Metal-Chelating Unnatural Amino Acid
  作者：Xiaohong Liu、Jiasong Li、Cheng Hu、Qing Zhou、Wei Zhang、Meirong Hu、Juanzuo Zhou、Jiangyun Wang

  DOI：10.1002/anie.201301307

  日期：2013.4.26

  red‐shifted: A novel metal‐chelating unnatural amino acid with an 8‐hydroxyquinoline group (HqAla) can be enzymatically incorporated into GFP (see scheme). Substituting a Tyr residue in the chromophore of FPs with HqAla results in significantly red‐shifted excitation and emission maxima. The crystal structure of superfolder GFP bearing HqAla in its chromophore shows the structural basis for these red

  发生红移：可以将一种具有8-羟基喹啉基（HqAla）的新型金属螯合非天然氨基酸酶促地整合到GFP中（参见方案）。用HqAla替代FPs发色团中的Tyr残基会导致极大的红移激发和发射最大值。在生色团中带有HqAla的GFP超级文件夹的晶体结构显示了这些红移的结构基础。
• 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
• [EN] NEUROPROTECTIVE IRON CHELATORS AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM<br/>[FR] CHELATEURS DU FER ET COMPOSITIONS PHARMACEUTIQUES LES RENFERMANT
  申请人：TECHNION RES & DEV FOUNDATION

  公开号：WO2004041151A2

  公开（公告）日：2004-05-21

  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.
• 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.