5-(benzyloxy)-2-methylpyridin-4(1H)-one | 958753-83-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-(benzyloxy)-2-methylpyridin-4(1H)-one
• 英文别名: 3-benzyloxy-6-methyl-pyridin-4(1H)-one；2-methyl-5-benzyloxypyridin-4(1H)-one；5-benzyloxy-2-methyl-4(1H)-pyridone；5-benzyloxy-2-methyl-1H-pyridin-4-one；2-methyl-5-phenylmethoxy-1H-pyridin-4-one
• CAS: 958753-83-8
• 化学式: C₁₃H₁₃NO₂
• mdl: MFCD20535503
• 分子量: 215.252
• InChiKey: KUXLNQVLYVVIJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(benzyloxy)-2-methylpyridin-4(1H)-one 在 sodium hypochlorite 、 potassium carbonate 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 5-(benzyloxy)-3-chloro-1,2-dimethylpyridin-4(1H)-one
  参考文献：
  名称：

  [EN] FLUORINATED DERIVATIVES OF 3-HYDROXYPYRIDIN-4-ONES
  [FR] DÉRIVÉS FLUORÉS DE 3-HYDROXYPYRIDIN-4-ONES

  摘要：

  提供的是Formula I的化合物，它们是3-羟基吡啶-4-酮的衍生物。这些化合物可用于治疗与铁的毒性浓度有关的医疗状况。这些化合物可用于制备用于治疗与铁的毒性浓度有关的医疗状况的药物。与铁的毒性浓度有关的医疗状况可从以下组中选择：癌症、肺部疾病、进行性肾病和弗里德里希共济失调。

  公开号：

  WO2011000104A1
• 作为产物：
  描述：

  2-乙基-3-苯基甲氧基吡喃-4-酮 在 ammonium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 12.0h， 生成 5-(benzyloxy)-2-methylpyridin-4(1H)-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of hydroxypyridinone-coumarin hybrids as multimodal monoamine oxidase B inhibitors and iron chelates against Alzheimer's disease

  摘要：

  A series of hybrids of hydroxypyridinone and coumarin were rationally designed, synthesized and biologically evaluated for their iron ion chelating and MAO-B inhibitory activities. Most of the compounds displayed excellent iron ion chelating effects and moderate to good anti-MAO-B activities. Compound 27a exhibited the most potent activity against MAO-B, with an IC50 value of 14.7 nM. Importantly, 27a showed good U251 cell protective effect and significantly ameliorated the cognitive dysfunction of scopolamine-induced AD mice. Moreover, molecular docking was performed to elucidate the probable ligand-receptor interaction, and the structure-activity relationships were also summarized. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.07.031

文献信息

• Prediction of 3-hydroxypyridin-4-one (HPO) log K1 values for Fe(iii)
  作者：Yu-Lin Chen、Dave J. Barlow、Xiao-Le Kong、Yong-Min Ma、Robert C. Hider

  DOI：10.1039/c2dt31254a

  日期：——

  As a means to aid in the design of 3-hydroxypyridin-4-ones (HPOs) intended for use as therapeutic Fe3+ chelating agents, a novel methodology has been developed using quantum mechanical (QM) calculations for predicting the iron binding affinities of the compounds (more specifically, their log K1 values). The reported/measured HPO log K1 values were verified through their correlation with the corresponding sum of the compounds’ ligating group pKa values. Using a training set of eleven HPOs with known log K1 values, reliable predictions are shown to be obtained with QM calculations using the B3LYP/6-31+G(d)/CPCM model chemistry (with Bondi radii, and water as solvent). With this methodology, the observed log K1 values for the training set compounds are closely matched by the predicted values, with the correlation between the observed and predicted values giving r2 = 0.9. Predictions subsequently made by this method for a test set of 42 HPOs of known log K1 values gave predicted values accurate to within ±0.32 log units. In order to further investigate the predictive power of the method, four novel HPOs were synthesised and their log K1 values were determined experimentally. Comparison of these predicted log K1 values against the measured values gave absolute deviations of 0.22 (13.87 vs. 14.09), 0.02 (14.31 vs. 14.29), 0.12 (14.62 vs. 14.50), and 0.13 (15.04 vs. 15.17). The prediction methodology reported here is the first to be provided for predicting the absolute log K1 values of iron-chelating agents in the absence of pKa values.

  为了帮助设计用于治疗的三羟基吡啶-4-酮（HPOs）作为Fe3+螯合剂，开发了一种新方法，利用量子力学（QM）计算预测化合物的铁结合亲和力（更具体地说，是它们的log K1值）。报告/测量的HPO log K1值通过与相应化合物配位基团pKa值和的总和的相关性得到验证。使用已知log K1值的十一种HPO作为训练集，通过采用B3LYP/6-31+G(d)/CPCM模型化学（以Bondi半径和水作为溶剂）进行QM计算，显示可以获得可靠的预测。使用这种方法，观察到的训练集化合物的log K1值与预测值紧密匹配，观察值与预测值之间的相关性为r2 = 0.9。随后，使用该方法对42种已知log K1值的HPO的预测值在±0.32 log单位内是准确的。为了进一步研究该方法的预测能力，合成了四种新型HPO，并对其log K1值进行了实验测定。将这些预测的log K1值与测量值进行比较，得到的绝对偏差为0.22（13.87对14.09）、0.02（14.31对14.29）、0.12（14.62对14.50）和0.13（15.04对15.17）。此处报告的预测方法是首个在没有pKa值的情况下预测铁螯合剂绝对log K1值的方法。
• 具有铁螯合和单胺氧化酶B抑制活性的香豆 素杂合吡啶酮类化合物及其制备与应用
  申请人：浙江工业大学

  公开号：CN110218207B

  公开（公告）日：2020-12-25

  本发明公开了一种如式(Ⅰ)所示的香豆素/吡啶酮杂合衍生物或其药学上可接受的盐，所述的香豆素/吡啶酮杂合衍生物的制备方法为：以式1所示的不同取代基的羟基吡喃酮为原料通过一系列合成得到式3所示的吡啶酮衍生物；以式4所示的化合物经过缩合反应得到如式5所示的化合物经一步溴代得到式6所示的化合物与式3所示的吡啶酮衍生物经过一步亲核取代反应得到如式7所示的化合物，最后脱除吡啶酮结构中的烷基保护基团得到式(I)所示的目标化合物。本发明提供的化合物是一类全新的单分子多靶点系列药物，具有铁螯合性也有靶向MAO‑B抑制活性以及抗氧化活性，对于发病机理复杂的阿尔兹海默病具有独到的优势，作用机制明确，活性优异。
• Fluorinated derivatives of deferiprone
  申请人：Tam Tim Fat

  公开号：US20080242706A1

  公开（公告）日：2008-10-02

  The present invention relates to novel derivatives of deferiprone. In particular, the present invention relates to fluorinated derivatives of deferiprone or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising same, processes for the manufacture thereof and their use in the treatment of neurodegenerative diseases caused by the presence of free iron or iron accumulation in neural tissues and in diseases wherein excess iron must be removed or redistributed.

  本发明涉及延胜肽的新颖衍生物。具体地，本发明涉及延胜肽的氟化衍生物或其药用盐，包括相同的药物组成部分，制造这些药物组成部分的方法以及它们在治疗由游离铁或神经组织中铁积累引起的神经退行性疾病以及需要去除或重新分配过量铁的疾病中的用途。
• FLUORINATED DERIVATES OF 3-HYDROXYPYRIDIN-4-ONES
  申请人：Tam Tim Fat

  公开号：US20120270882A1

  公开（公告）日：2012-10-25

  Provided are compounds of Formula I which are derivatives of 3-Hydroxypyridin-4-ones. The compounds may be used in treatment of a medical condition related to a toxic concentration of iron. The compounds may be used for preparation of a medicament for treatment of a medical condition related to a toxic concentration of iron. The medical condition related to a toxic concentration of iron may be selected from the group consisting of: cancer, pulmonary disease, progressive kidney disease and Frederich's Ataxia.

  提供的是公式I的化合物，它们是3-羟基吡啶-4-酮的衍生物。这些化合物可以用于治疗与铁的毒性浓度相关的医疗状况。这些化合物可以用于制备治疗与铁的毒性浓度相关的医疗状况的药物。与铁的毒性浓度相关的医疗状况可以从以下组中选择：癌症、肺部疾病、进行性肾脏疾病和弗里德里希共济失调症。
• Fluorinated Derivatives of Deferiprone
  申请人：Tam Tim Fat

  公开号：US20120095061A1

  公开（公告）日：2012-04-19

  The present invention relates to novel derivatives of deferiprone. In particular, the present invention relates to fluorinated derivatives of deferiprone or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising same, processes for the manufacture thereof and their use in the treatment of neurodegenerative diseases caused by the presence of free iron or iron accumulation in neural tissues and in diseases wherein excess iron must be removed or redistributed.

  本发明涉及新型去铁酮衍生物。特别地，本发明涉及氟化去铁酮衍生物或其药学上可接受的盐、包含其的制药组合物、其制造过程以及在治疗由自由铁或神经组织中铁积累引起的神经退行性疾病和需要去除或重新分配过量铁的疾病中的应用。