2-(dimethylamino)methyl-8-hydroxyquinoline | 1428417-49-5

• 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-(dimethylamino)methyl-8-hydroxyquinoline
• 英文别名: 2-[(Dimethylamino)methyl]-8-hydroxyquinoline；2-[(dimethylamino)methyl]quinolin-8-ol
• CAS: 1428417-49-5
• 化学式: C₁₂H₁₄N₂O
• 分子量: 202.256
• InChiKey: VEEBMVNHFKHDHV-UHFFFAOYSA-N

物化性质

• 沸点：
  324.7±27.0 °C(Predicted)
• 密度：
  1.177±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  36.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(dimethylamino)methyl-8-hydroxyquinoline 在 盐酸 作用下， 以 甲醇 、 水 为溶剂， 生成 2-[(dimethylamino)methyl]-8-hydroxyquinoline hydrochloride
  参考文献：
  名称：

  Mixed Ligand Cu²⁺ Complexes of a Model Therapeutic with Alzheimer’s Amyloid-β Peptide and Monoamine Neurotransmitters

  摘要：

  8-Hydroxyquinolines (8HQ) have found widespread application in chemistry and biology due to their ability to complex a range of transition metal ions. The family of 2-substituted 8HQs has been proposed for use in the treatment of Alzheimer's disease (AD). Most notably, the therapeutic PBT2 (Prana Biotechnology Ltd.) has been shown to act as an efficient metal chaperone, disaggregate metal-enriched amyloid plaques comprised of the A beta peptide, inhibit Cu/A beta redox chemistry, and reverse the AD phenotype in transgenic animal models. Yet surprisingly little is known about the molecular interactions at play. In this study, we show that the homologous ligand 2-[(dimethylamino)methyl]-8-hydroxyquinoline (HL) forms a CuL complex with a conditional (apparent) dissociation constant of 0.33 nM at pH 6.9 and is capable of forming ternary Cu2+ complexes with neurotransmitters including histamine (HA), glutamic acid (Glu), and glycine (Gly), with glutathione disulfide (GSSG), and with histidine (His) side chains of proteins and peptides including the A beta peptide. Our findings suggest a molecular basis for the strong metal chaperone activity of PBT2, its ability to attenuate Cu2+/A beta interactions, and its potential to promote neuroprotective and neuroregenerative effects.

  DOI：

  10.1021/ic302289r
• 作为产物：
  描述：

  8-羟基喹啉-2-甲醛 、 二甲胺 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以180 mg的产率得到2-(dimethylamino)methyl-8-hydroxyquinoline
  参考文献：
  名称：

  Mixed Ligand Cu²⁺ Complexes of a Model Therapeutic with Alzheimer’s Amyloid-β Peptide and Monoamine Neurotransmitters

  摘要：

  8-Hydroxyquinolines (8HQ) have found widespread application in chemistry and biology due to their ability to complex a range of transition metal ions. The family of 2-substituted 8HQs has been proposed for use in the treatment of Alzheimer's disease (AD). Most notably, the therapeutic PBT2 (Prana Biotechnology Ltd.) has been shown to act as an efficient metal chaperone, disaggregate metal-enriched amyloid plaques comprised of the A beta peptide, inhibit Cu/A beta redox chemistry, and reverse the AD phenotype in transgenic animal models. Yet surprisingly little is known about the molecular interactions at play. In this study, we show that the homologous ligand 2-[(dimethylamino)methyl]-8-hydroxyquinoline (HL) forms a CuL complex with a conditional (apparent) dissociation constant of 0.33 nM at pH 6.9 and is capable of forming ternary Cu2+ complexes with neurotransmitters including histamine (HA), glutamic acid (Glu), and glycine (Gly), with glutathione disulfide (GSSG), and with histidine (His) side chains of proteins and peptides including the A beta peptide. Our findings suggest a molecular basis for the strong metal chaperone activity of PBT2, its ability to attenuate Cu2+/A beta interactions, and its potential to promote neuroprotective and neuroregenerative effects.

  DOI：

  10.1021/ic302289r

文献信息

• Enantiomers of 8-hydroxyquinoline derivatives and the synthesis thereof
  申请人：AVIDIN Co. Ltd.

  公开号：US10287265B2

  公开（公告）日：2019-05-14

  Our invention relates to novel enantiomer derivatives of 8-hydroxyquinoline derivatives with general formula (I) and (II) and the synthesis thereof and pharmaceutically acceptable salts and metal complexes thereof, and the medicinal and/or pharmaceutical compositions comprising these compounds. The essence of the subject matter of the invention relates to the fact that prior art discloses the biological effect and characteristics only of the racemic products, the novel enantiomer derivatives according to the invention appear in our application for the first. The subject matter of the invention furthermore relates to a novel, stereoselective synthesis for the preparation of the novel enantiomer derivatives according to the invention. The novel medicinal and/or pharmaceutical compositions comprising these enantiomers are suitable for the treatment of the named diseases, and the enanatiomers are used for manufacture of these compositions. These applications for manufacture of the compositions are also the subject matters of the invention. The compounds according to the invention can be used preferably as cytoprotective, neuroprotective, cardioprotective, anxiolytic and antidepressant agent for treatment of neuropsychiatric and neurologic diseases and diseases in connections with transplantations and with ischemia and reperfusion injuries thereof, and inhibition of organ, advantageously skin graft rejection. According to our studies the R-enantiomer has either sole or high biological effect in some cases.

  我们的发明涉及通式（I）和（II）的 8-羟基喹啉衍生物的新型对映体衍生物及其合成、其药用盐和金属络合物，以及包含这些化合物的药用和/或药物组合物。 本发明主题的实质在于，现有技术仅公开了外消旋产物的生物效应和特征，而根据本发明的新型对映体衍生物在我们的申请中首次出现。 本发明的主题还涉及一种用于制备本发明新型对映体衍生物的新型立体选择性合成方法。由这些对映体组成的新型药物和/或医药组合物适用于治疗上述疾病，而对映体则用于制造这些组合物。这些组合物的制造应用也是本发明的主题。根据本发明的化合物可优先用作细胞保护剂、神经保护剂、心脏保护剂、抗焦虑剂和抗抑郁剂，用于治疗神经精神疾病和神经系统疾病以及与移植有关的疾病及其缺血和再灌注损伤，并抑制器官、尤其是皮肤移植的排斥反应。根据我们的研究，R-对映体在某些情况下具有唯一或较高的生物效应。
• [EN] ENANTIOMERS OF 8-HYDROXY QUINOLINE DERIVATIVES AND THE SYNTHESIS THEREOF<br/>[FR] ÉNANTIOMÈRES DE DÉRIVÉS DE 8-HYDROXYQUINOLINE, ET SYNTHÈSE DE CEUX-CI
  申请人：AVIDIN CO LTD

  公开号：WO2016162706A9

  公开（公告）日：2016-11-17
• ENANTIOMERS OF 8-HYDROXY QUINOLINE DERIVATIVES AND THE SYNTHESIS THEREOF
  申请人：Avidin Co. Ltd.

  公开号：EP3268357A1

  公开（公告）日：2018-01-17
• ENANTIOMERS OF 8-HYDROXYQUINOLINE DERIVATIVES AND THE SYNTHESIS THEREOF
  申请人：AVIDIN Co. Ltd.

  公开号：US20170197936A1

  公开（公告）日：2017-07-13

  Our invention relates to novel enantiomer derivatives of 8-hydroxyquinoline derivatives with general formula (I) and (II) and the synthesis thereof and pharmaceutically acceptable salts and metal complexes thereof, and the medicinal and/or pharmaceutical compositions comprising these compounds. The essence of the subject matter of the invention relates to the fact that prior art discloses the biological effect and characteristics only of the racemic products, the novel enantiomer derivatives according to the invention appear in our application for the first. The subject matter of the invention furthermore relates to a novel, stereoselective synthesis for the preparation of the novel enantiomer derivatives according to the invention. The novel medicinal and/or pharmaceutical compositions comprising these enantiomers are suitable for the treatment of the named diseases, and the enanatiomers are used for manufacture of these compositions. These applications for manufacture of the compositions are also the subject matters of the invention. The compounds according to the invention can be used preferably as cytoprotective, neuroprotective, cardioprotective, anxiolytic and antidepressant agent for treatment of neuropsychiatric and neurologic diseases and diseases in connections with transplantations and with ischemia and reperfusion injuries thereof, and inhibition of organ, advantageously skin graft rejection. According to our studies the R-enantiomer has either sole or high biological effect in some cases.
• Mixed Ligand Cu²⁺ Complexes of a Model Therapeutic with Alzheimer’s Amyloid-β Peptide and Monoamine Neurotransmitters
  作者：Vijaya B. Kenche、Izabela Zawisza、Colin L. Masters、Wojciech Bal、Kevin J. Barnham、Simon C. Drew

  DOI：10.1021/ic302289r

  日期：2013.4.15

  8-Hydroxyquinolines (8HQ) have found widespread application in chemistry and biology due to their ability to complex a range of transition metal ions. The family of 2-substituted 8HQs has been proposed for use in the treatment of Alzheimer's disease (AD). Most notably, the therapeutic PBT2 (Prana Biotechnology Ltd.) has been shown to act as an efficient metal chaperone, disaggregate metal-enriched amyloid plaques comprised of the A beta peptide, inhibit Cu/A beta redox chemistry, and reverse the AD phenotype in transgenic animal models. Yet surprisingly little is known about the molecular interactions at play. In this study, we show that the homologous ligand 2-[(dimethylamino)methyl]-8-hydroxyquinoline (HL) forms a CuL complex with a conditional (apparent) dissociation constant of 0.33 nM at pH 6.9 and is capable of forming ternary Cu2+ complexes with neurotransmitters including histamine (HA), glutamic acid (Glu), and glycine (Gly), with glutathione disulfide (GSSG), and with histidine (His) side chains of proteins and peptides including the A beta peptide. Our findings suggest a molecular basis for the strong metal chaperone activity of PBT2, its ability to attenuate Cu2+/A beta interactions, and its potential to promote neuroprotective and neuroregenerative effects.