3-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-4H-chromen-4-one | 159184-95-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 3-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-4H-chromen-4-one
• 英文别名: 3'-methoxy-4'-hydroxyflavonol；3-hydroxy-2-(4-hydroxy-3-methoxyphenyl)chromen-4-one
• CAS: 159184-95-9
• 化学式: C₁₆H₁₂O₅
• 分子量: 284.268
• InChiKey: YONDROKMQHIDPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-苄氧基-3-甲氧基苯甲醛 在 茴香硫醚 、 双氧水 、 三氟乙酸 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 8.0h， 生成 3-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-4H-chromen-4-one
  参考文献：
  名称：

  Exploration of Pharmacophore in Chrysosplenol C as Activator in Ventricular Myocyte Contraction

  摘要：

  Chrysosplenol C (4',5,6-trihydroxy-3,3',7-tri-methoxyflavone) isolated from Miliusa balansae has unique structural features as a reversible inotropic agent independent of beta-adrenergic signaling and with selective activation of cardiac myosin ATPase. Hence, a series of chrysosplenol analogues were synthesized and explored for identification of pharmacophore that is essential for the increasing contractility in rat ventricular myocytes. Analogue 7-chloro-2-(3-hydroxypheny1)-3-methoxy-4H-chromen-4-one showed highly potent contractility (54.8% at 10 mu M) through activating cardiac myosin ATPase (38.7% at 10 mu M). Our systematic structure activity relationship study revealed that flavonoid nucleus of chrososplenol C appears to be an essential basic skeleton and hydrophobic substituent at position 7 of chromenone such as methoxy or chloro enhances the activity. Additionally, our ATPase study suggested that these chrysosplenol analogues have selectivity toward cardiac myosin activation. Thus, the novel flavonone with 3-/7-hydrophobic substituent and 3'-hydrogen bonding donor function is a novel scaffold for discovery of a new positive inotropic agent.

  DOI：

  10.1021/acsmedchemlett.5b00043

文献信息

• Design, synthesis and biological activity of flavonoid derivatives as selective agonists for neuromedin U 2 receptor
  作者：Ming-Liang Ma、Ming Li、Jiao-Jiao Gou、Tian-Yu Ruan、Hai-Shan Jin、Ling-Hong Zhang、Liang-Chun Wu、Xiao-Yan Li、Ying-He Hu、Ke Wen、Zheng Zhao

  DOI：10.1016/j.bmc.2014.08.038

  日期：2014.11

  Central neuromedin U 2 receptor (NMU2R) plays important roles in the regulation of food intake and body weight. Identification of NMU2R agonists may lead to the development of pharmaceutical agents to treat obesity. Based on the structure of rutin, a typical flavonoid and one of the NMU2R agonists we previously identified from an in-house made natural product library, 30 flavonoid derivatives have been synthesized and screened on a cell-based reporter gene assay. A number of compounds were found to be selective and highly potent to NMU2R. For example, the EC50 value of compound NRA 4 is very close to that of NMU, the endogenous peptide ligand of NMU2R. Structure-activity relationship analysis revealed that a 3-hydroxyl group in ring C and a 2'-fluoride group in ring B were essential for this class of compounds to be active against NMU2R. (C) 2014 Elsevier Ltd. All rights reserved.
• Understanding the Cardioprotective Effects of Flavonols: Discovery of Relaxant Flavonols without Antioxidant Activity
  作者：Cheng Xue Qin、Xingqiang Chen、Richard A. Hughes、Spencer J. Williams、Owen L. Woodman

  DOI：10.1021/jm070352h

  日期：2008.3.1

  3 ',4 '-Dihydroxyflavonol (DiOHF) is a cardioprotective flavonol that can reduce injury after myocardial ischemia and reperfusion and thus is a promising small molecule for the treatment of cardiovascular disease. Like all vasoactive flavonols reported to date, DiOHF is both relaxant and antioxidant, hindering investigation of the relative contribution of each activity for the prevention of reperfusion injury. This study investigates structure-activity relationships of variations at the 3 ' and 4 ' positions of the B ring of DiOHF and vasorelaxant and antioxidant activities. Relaxation of rat isolated aortic rings precontracted with KCl revealed that the most active flavonols were those with a 4 '-hydroxyl group, with the opening of potassium channels as a possible contributing mechanism. For the antioxidant activity, with the exception of DiOHF, none of the flavonols investigated were able to significantly scavenge superoxide radical, and none of the three most potent vasorelaxant flavonols could prevent oxidant-induced endothelial dysfunction. The discovery of single-acting vasorelaxant flavonols without antioxidant activity, in particular 4 '-hydroxy-3 '-methoxyflavonol, will assist in investigating the mechanism of flavonol-induced cardioprotection.
• 3′-Hydroxy-3,4′-dimethoxyflavone blocks tubulin polymerization and is a potent apoptotic inducer in human SK-MEL-1 melanoma cells
  作者：Francisco Estévez-Sarmiento、Mercedes Said、Ignacio Brouard、Francisco León、Celina García、José Quintana、Francisco Estévez

  DOI：10.1016/j.bmc.2017.09.043

  日期：2017.11

  Flavonoids are naturally occurring polyphenolic compounds and are among the most promising anticancer agents. A series of flavonols and their 3-methyl ether derivatives were synthesized and assessed for cytotoxicity. It was found that 3'-hydroxy-3,4'-dimethoxyflavone (flavonoid 7a) displayed strong cytotoxicity against human SK-MEL-1 melanoma cells and blocked tubulin polymerization, but had no significant cytotoxic effects against quiescent or proliferating human peripheral blood mononuclear cells. Our analyses showed that flavonoid 7a induces G2-M cell cycle arrest and apoptosis in melanoma cells which is associated with cytochrome c release and activation of both extrinsic and intrinsic apoptotic pathways of cell death. (C) 2017 Elsevier Ltd. All rights reserved.
• UTILISATION D'UNE ASSOCIATION DE DEUX COMPOSÉS POUR LE TRAITEMENT ET/OU LA PRÉVENTION DE TROUBLES OSSEUX
  申请人：Institut National de la Recherche Agronomique (INRA)

  公开号：EP2999467B1

  公开（公告）日：2020-01-08
• NEUROPROTECTIVE POLYPHENOL ANALOGS
  申请人：Salk Institute for Biological Studies

  公开号：US20140186328A1

  公开（公告）日：2014-07-03

  The present invention provides neuroprotective polyphenol compounds, which can be synthetic analogs of fisetin, baicalein or chlorogenic acid, that maintain neuroprotective, anti-inflammatory, glutathione promoting, and/or antioxidant properties. The neuroprotective polyphenol compounds are useful for promoting, enhancing and/or increasing neuron protection, growth and/or regeneration. The polyphenol compounds further find use for increasing and or maintaining intracellular glutathione (GSH) levels. The polyphenol compounds are also useful for treating, preventing, mitigating and/or delaying neurodegenerative conditions, including diabetes, Parkinson's disease, Huntington's disease, Alzheimer's disease, non-Alzheimer's dementias, multiple sclerosis, traumatic brain injury, spinal cord injury or ALS.

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