3-(溴甲基)-7-甲氧基-2H-色烯-2-酮 | 133932-20-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 中文名称: 3-(溴甲基)-7-甲氧基-2H-色烯-2-酮
• 英文名称: 3-(bromomethyl)-7-methoxy-2H-chromen-2-one
• 英文别名: 3-bromomethyl-7-methoxy-2H-chromen-2-one；3-(bromomethyl)-7-methoxycoumarin；7-methoxy-3-bromomethylcoumarin；3-(bromomethyl)-7-methoxychromen-2-one
• CAS: 133932-20-4
• 化学式: C₁₁H₉BrO₃
• 分子量: 269.095
• InChiKey: CMOYFLHIGAOGTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(溴甲基)-7-甲氧基-2H-色烯-2-酮 在 三氯化硼 、 potassium carbonate 作用下， 以 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 14.0h， 生成 2-methyl-5-hydroxy-1-((7-methoxycoumarin-3-yl)methyl)pyridin-4(1H)-one
  参考文献：
  名称：

  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

  摘要：

  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。

  公开号：

  CN110218207B
• 作为产物：
  描述：

  3-甲氧基苯酚 在 N-溴代丁二酰亚胺(NBS) 、 磷酸 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 反应 3.5h， 生成 3-(溴甲基)-7-甲氧基-2H-色烯-2-酮
  参考文献：
  名称：

  Fluorescent markers for hypoxic cells: a study of nitroaromatic compounds, with fluorescent heterocyclic side chains, that undergo bioreductive binding

  摘要：

  Several novel compounds having both a 2-nitroimidazole nucleus and a fluorescent ring system in their molecular structure were prepared and evaluated as potential fluorescent probes for hypoxia. Bioreduction of nitroimidazoles, which is inhibited by oxygen, is known to lead to binding of bioreductive metabolites to cellular macromolecules and this provides a mechanism for binding the fluorescent moiety to hypoxic cells. These compounds can incorporate a wide range of fluorophors and can therefore be designed to suit the laser-line wavelengths available for excitation of fluorescence in the flow cytometer. Several nitroimidazoles with naphthalimide side chains were rapidly taken up into cells and became concentrated in the cells, thus reducing their concentration in the extracellular medium. This suggests a potential microscopic bioavailability problem with probes of this type when used in vivo as they would become progressively depleted in the extracellular fluid as they diffused from blood vessels, through layers of packed cells in tumors, to the hypoxic cells where they could undergo hypoxia-specific metabolism. Synthesis of nitroimidazoles with coumarin fluorophors led to several potentially useful probes for hypoxia; substituents on the coumarin fluorophor had a marked effect on the cellular fluorescence of these compounds.

  DOI：

  10.1021/jm00111a049

文献信息

• Searching for Multi-Targeting Neurotherapeutics against Alzheimer’s: Discovery of Potent AChE-MAO B Inhibitors through the Decoration of the 2H-Chromen-2-one Structural Motif
  作者：Leonardo Pisani、Roberta Farina、Ramon Soto-Otero、Nunzio Denora、Giuseppe Mangiatordi、Orazio Nicolotti、Estefania Mendez-Alvarez、Cosimo Altomare、Marco Catto、Angelo Carotti

  DOI：10.3390/molecules21030362

  日期：——

  vitro inhibitory activities against MAO-B. Within this series, derivative 3h emerged as the most interesting hit compound, being a moderate AChE inhibitor (IC50 = 8.99 µM) and a potent and selective MAO-B inhibitor (IC50 = 2.8 nM). Preliminary studies in human neuroblastoma SH-SY5Y cell lines demonstrated its low cytotoxicity and disclosed a promising neuroprotective effect at low doses (0.1 µM) under oxidative

  对开发针对神经退行性综合症，尤其是阿尔茨海默氏病（AD）的真正的疾病缓解药物的需求，使研究转向可靠的药物发现策略，以揭示具有比单靶标药物更高的治疗功效的临床候选药物。通过遵循多目标方法，我们设计和合成了新型的双乙酰胆碱酯酶（AChE）-单胺氧化酶B（MAO-B）抑制剂，通过装饰2H-chromen-2-one骨架。在位置3带有炔丙基胺部分的化合物在体外对MAO-B表现出最高的抑制活性。在该系列中，衍生物3h成为最有趣的命中化合物，是中度AChE抑制剂（IC50 = 8.99 µM）和有效且选择性的MAO-B抑制剂（IC50 = 2.8 nM）。对人类神经母细胞瘤SH-SY5Y细胞系的初步研究表明，它具有较低的细胞毒性，并揭示了在两种线粒体毒素（寡霉素-A和鱼藤酮）促进的氧化应激条件下，低剂量（0.1 µM）下有希望的神经保护作用。在基于Madin-Darby犬肾（MDCK）II-MDR1细
• Design, Synthesis, and 3D QSAR of Novel Potent and Selective Aromatase Inhibitors
  作者：Francesco Leonetti、Angelo Favia、Angela Rao、Rosaria Aliano、Anja Paluszcak、Rolf W. Hartmann、Angelo Carotti

  DOI：10.1021/jm049535j

  日期：2004.12.1

  imidazole or triazole ring linked to a fluorene (A), indenodiazine (B), or coumarin scaffold (C) are reported. Properly substituted coumarin derivatives displayed the highest aromatase inhibitory potency and selectivity over 17-alpha-hydroxylase/17-20 lyase. The modeling of the aromatase inhibition data by Comparative Molecular Field Analysis (CoMFA/GOLPE 3D QSAR approach) led to the development of a PLS

  报道了一系列新的芳香酶抑制剂的设计，合成和生物学评估，这些抑制剂带有与芴（A），茚并二嗪（B）或香豆素骨架（C）连接的咪唑或三唑环。与17-α-羟化酶/ 17-20裂解酶相比，正确取代的香豆素衍生物显示出最高的芳香酶抑制能力和选择性。通过比较分子场分析（CoMFA / GOLPE 3D QSAR方法）对芳香化酶抑制数据进行建模，导致了具有良好拟合和预测能力（n = 22，ONC = 3，r（2）= 0.949， s = 0.216，而q（2）= 0.715）。
• Determination of Key Hydrocarbon Autoxidation Products by Fluorescence
  作者：Ron Shah、Derek A. Pratt

  DOI：10.1021/acs.joc.6b01032

  日期：2016.8.5

  system compatible with heavy hydrocarbons. The latter can be used directly with our previously described hydroperoxide-sensitive coumarin-conjugated phosphine probe to enable rapid quantification of both carboxylic acids and hydroperoxides in hydrocarbon samples. The utility of the approach is illustrated by the ready determination of the differing relative rates of hydroperoxide and acid formation with

  氢过氧化物和羧酸是碳氢化合物自氧化过程中产生的主要主要产物。我们已经开发出一种简单的方法，可以使用与基于非极性香豆素和BODIPY的荧光团偶联的氢过氧化物和酸敏感部分，快速，同时确定两种类型的产品。在与重质烃相容的溶剂系统中进行质子化后，本文所述的香豆素和BODIPY共轭的胺探针分别经历了38倍和8倍的增强。后者可以直接与我们先前描述的氢过氧化物敏感性香豆素共轭膦探针一起使用，从而能够快速定量烃样品中的羧酸和氢过氧化物。正十六烷对1-十六烯对润滑剂基础油）。与常见但费力的滴定方法相比，该方法具有显着的多功能性和自动化性，并且大大提高了用于高温应用的新型自由基捕获抗氧化剂的鉴定效率和准确性。通过自动分析24种受抑制的润滑油自氧化反应的样品中的氢过氧化物和羧酸（通过酶标仪）进行自动化分析，证明了这一应用，该反应在平行合成器中于160°C上一天进行三次。
• Photoresist underlayer film-forming composition and pattern forming process
  申请人：Shin-Etsu Chemical Co., Ltd.

  公开号：EP2813891A2

  公开（公告）日：2014-12-17

  In lithography, a composition comprising a novolak resin comprising recurring units of hydroxycoumarin is used to form a photoresist underlayer film. The underlayer film is strippable in alkaline water, without causing damage to ion-implanted Si substrates or SiO2 substrates.

  在光刻技术中，一种由包含羟基香豆素递归单元的酚醛树脂组成的组合物可用于形成光刻胶底层膜。该底层膜可在碱水中剥离，而不会对离子注入硅基底或二氧化硅基底造成损坏。
• Design, synthesis and biological evaluation of hydroxypyridinone-coumarin hybrids as multimodal monoamine oxidase B inhibitors and iron chelates against Alzheimer's disease
  作者：Changjun Zhang、Ke Yang、Sihang Yu、Jing Su、Shengli Yuan、Jiaxin Han、Yan Chen、Jinping Gu、Tao Zhou、Renren Bai、Yuanyuan Xie

  DOI：10.1016/j.ejmech.2019.07.031

  日期：2019.10

  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.