8-hydroxy-5H-chromeno[2,3-b]pyridin-5-one | 54629-19-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 8-hydroxy-5H-chromeno[2,3-b]pyridin-5-one
• 英文别名: 8-hydroxy-chromeno[2,3-b]pyridin-5-one；8-Hydroxychromeno[2,3-b]pyridin-5-one
• CAS: 54629-19-5
• 化学式: C₁₂H₇NO₃
• 分子量: 213.192
• InChiKey: QURCVMZKUKUAGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-hydroxy-5H-chromeno[2,3-b]pyridin-5-one 在 potassium carbonate 、 三乙胺 、 sodium iodide 作用下， 以 丙酮 、 甲苯 、 丁酮 为溶剂， 反应 3.0h， 生成 8-(3-((3-hydroxybenzyl)(methyl)amino)propoxy)-5H-chromeno[2,3-b]pyridin-5-one
  参考文献：
  名称：

  脂肪酸酰胺水解酶（FAAH），乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）：氨基甲酸酯作为潜在的抗阿尔茨海默氏病病原体发展的网络化目标

  摘要：

  内源性大麻素系统的调节正在成为治疗神经退行性疾病的可行途径，参与神经保护和抗炎过程。特别地，通过FAAH抑制间接增强内源性大麻素信号传导至治疗水平可能有益于神经退行性疾病，例如阿尔茨海默氏病，有效预防或减慢疾病的发展。因此，在寻找更有效的阿尔茨海默氏病治疗方法中，本文将多目标导向的配体范式用于氨基甲酸酯的设计，该氨基甲酸酯能够同时靶向最近提出的内源性大麻素系统和经典的胆碱酯酶系统，并实现有效的双重治疗。 FAAH /胆碱酯酶抑制剂。在这两个合成的化合物系列中，9和19被确定为有效的双重FAAH / ChE抑制剂，具有均衡的纳摩尔活性。因此，9和19可被视为阿尔茨海默氏病治疗的新有希望的候选者。

  DOI：

  10.1021/acs.jmedchem.6b00609
• 作为产物：
  描述：

  8-methoxy-chromeno[2,3-b]pyridin-5-one 以59%的产率得到
  参考文献：
  名称：

  VILLANI F. J.; MANN T. A.; WEFER E. A.; HANNON J.; LARCA L. L.; LANDON M.+, J. MED. CHEM. , 1975, 18, NO 1, 1-8

  摘要：

  DOI：

文献信息

• Acetylcholinesterase Inhibitors:  Synthesis and Structure−Activity Relationships of ω-[<i>N</i>-Methyl-<i>N</i>-(3-alkylcarbamoyloxyphenyl)- methyl]aminoalkoxyheteroaryl Derivatives
  作者：Angela Rampa、Alessandra Bisi、Piero Valenti、Maurizio Recanatini、Andrea Cavalli、Vincenza Andrisano、Vanni Cavrini、Lorena Fin、Alessandro Buriani、Pietro Giusti

  DOI：10.1021/jm9810046

  日期：1998.10.1

  Acetylcholinesterase (AChE) inhibitors are one of the most actively investigated classes of compounds in the search for an effective treatment of Alzheimer's disease. This work describes the synthesis, AChE inhibitory activity, and structure-activity relationships of some compounds related to a recently discovered series of AChE inhibitors: the omega-[N-methyl-N-(3-alkylcarbamoyloxyphenyl)methyl]aminoalkoxyxanthen-9-ones. The influence of structural variations on the inhibitory potency was carefully investigated by modifying different parts of the parent molecule, and a theoretical model of the binding of one representative compound to the enzyme was developed. The biological properties of the series were investigated in some detail by considering not only the activity on isolated enzyme but the selectivity with respect to butyrylcholinesterase (BuChE) and the in vitro inhibitory activity on rat cerebral cortex as well. Some of the newly synthesized derivatives, when tested on isolated and/or AChE-enriched rat brain cortex fraction, displayed a selective inhibitory activity and were more active than physostigmine. In particular, compound 13, an azaxanthone derivative, displayed the best rat cortex AChE inhibition (190-fold higher than physostigmine), as well as a high degree of enzyme selectivity (over 60-fold more selective for AChE than for BuChE). When tested in the isolated enzyme, compound 13 was less active, suggesting some differences either in drug availability/biotransformation or in the inhibitor-sensitive residues of the enzyme when biologically positioned in rat brain membranes.
• Benzopyranopyridine derivatives. 1. Aminoalkyl derivatives of the azaxanthenes as bronchodilating agents
  作者：Frank J. Villani、Thomas A. Mann、Elizabeth A. Wefer、Janet Hannon、Louis L. Larca、Mildred J. Landon、William Spivak、Dhiru Vashi、Salvatore Tozzi

  DOI：10.1021/jm00235a001

  日期：1975.1

  The preparation of the four isomeric azaxanthones 3 and a number of their aromatic ring substituted derivatives is described. These ketones were converted into the title compounds which were examined for their biological properties. The most interesting compound in this series, the 1-methyl-4-piperidylidene derivative of 1-azaxanthene, shows the profile of an orally effective potent bronchodilating agent as well as a moderate antihistamine. Biological properties of this compound were compared to a number of antihistamines as well as known bronchodilating agents. Structure-activity relationships are also discussed.
• Fatty Acid Amide Hydrolase (FAAH), Acetylcholinesterase (AChE), and Butyrylcholinesterase (BuChE): Networked Targets for the Development of Carbamates as Potential Anti-Alzheimer’s Disease Agents
  作者：Serena Montanari、Laura Scalvini、Manuela Bartolini、Federica Belluti、Silvia Gobbi、Vincenza Andrisano、Alessia Ligresti、Vincenzo Di Marzo、Silvia Rivara、Marco Mor、Alessandra Bisi、Angela Rampa

  DOI：10.1021/acs.jmedchem.6b00609

  日期：2016.7.14

  a viable avenue for the treatment of neurodegeneration, being involved in neuroprotective and anti-inflammatory processes. In particular, indirectly enhancing endocannabinoid signaling to therapeutic levels through FAAH inhibition might be beneficial for neurodegenerative disorders such as Alzheimer’s disease, effectively preventing or slowing the progression of the disease. Hence, in the search for

  内源性大麻素系统的调节正在成为治疗神经退行性疾病的可行途径，参与神经保护和抗炎过程。特别地，通过FAAH抑制间接增强内源性大麻素信号传导至治疗水平可能有益于神经退行性疾病，例如阿尔茨海默氏病，有效预防或减慢疾病的发展。因此，在寻找更有效的阿尔茨海默氏病治疗方法中，本文将多目标导向的配体范式用于氨基甲酸酯的设计，该氨基甲酸酯能够同时靶向最近提出的内源性大麻素系统和经典的胆碱酯酶系统，并实现有效的双重治疗。 FAAH /胆碱酯酶抑制剂。在这两个合成的化合物系列中，9和19被确定为有效的双重FAAH / ChE抑制剂，具有均衡的纳摩尔活性。因此，9和19可被视为阿尔茨海默氏病治疗的新有希望的候选者。
• VILLANI F. J.; MANN T. A.; WEFER E. A.; HANNON J.; LARCA L. L.; LANDON M.+, J. MED. CHEM. <JMCM-AR>, 1975, 18, NO 1, 1-8
  作者：VILLANI F. J.、 MANN T. A.、 WEFER E. A.、 HANNON J.、 LARCA L. L.、 LANDON M.+

  DOI：——

  日期：——