2-acetyl-3,5-dimethoxyphenyl 3,4-dimethoxybenzoate | 71847-56-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 缩酚酸和缩酚酸环醚类
• 英文名称: 2-acetyl-3,5-dimethoxyphenyl 3,4-dimethoxybenzoate
• 英文别名: 2-Veratroyloxy-4,6-dimethoxyacetophenon；(2-acetyl-3,5-dimethoxyphenyl) 3,4-dimethoxybenzoate
• CAS: 71847-56-8
• 化学式: C₁₉H₂₀O₇
• 分子量: 360.364
• InChiKey: KNMYQLMTNGZBAR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  80.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-acetyl-3,5-dimethoxyphenyl 3,4-dimethoxybenzoate 在 吡啶 、 硫酸 、 三溴化硼 、 溶剂黄146 、 potassium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 木犀草素
  参考文献：
  名称：

  新型合成的黄酮衍生物可为增强抗增殖活性所需的结构特征提供重要见解†

  摘要：

  随着许多癌症显示出对当前化学疗法的抗性，寻找新型抗癌药引起了极大的关注。天然类黄酮已被确认为此类计划的有用线索。然而，由于通常缺乏对最佳活性的结构要求的深入了解，因此在实现类黄酮作为抗增殖剂的全部潜力之前，需要进行进一步的研究。本文构建了一个包含76个甲氧基和羟基黄酮及其4-硫代类似物的宽泛文库，并建立了它们与乳腺癌细胞系MCF-7（ER + ve），MCF-7 /的抗增殖活性的结构-活性关系。探测了DX（ER + ve，抗蒽环类）和MDA-MB-231（ER -ve）。在该库中，有42种化合物是新颖的，所有化合物的收率都很高，纯度95％。最有前途的先导化合物，特别是新型羟基4-硫代黄酮美国国家癌症研究所（NCI）进一步评估了15f和16f对多种癌细胞系的抗增殖活性，并显示出显着的生长抑制特征（例如化合物15f：MCF-7（GI 50 = 0.18μM），T-47D（GI 50 = 0.03μM）和MDA-MB-468（GI

  DOI：

  10.1039/c6ra11041j
• 作为产物：
  描述：

  2-羟基-4,6-二甲氧基苯乙酮 、 藜芦酸 在 4-吡咯烷基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 2-acetyl-3,5-dimethoxyphenyl 3,4-dimethoxybenzoate
  参考文献：
  名称：

  具有癌症预防和治疗潜力的苯并吡喃 4-酮的一锅法合成

  摘要：

  描述了新型苯并吡喃-4-酮的一锅合成。在串联反应中，有机碱催化 (RCOCH2COR2)-C-1 在色酮-3-羧酸上的迈克尔加成导致后者的脱羧和吡喃-4-一环开环。当R-1是邻羟基芳基时，随后是色酮-和/或色满酮环闭合所得迈克尔加合物。14 种衍生物的抗氧化测试确定了色满酮 3o-r 的强抗自由基特性（DPPH 测定中为 2.1-3.1 微摩尔 Trolox 当量/微摩尔化合物）。Chromanones 3p 和 3r 以及 2-styrylchromone 3k 在报告基因测定中诱导细胞保护性 Keap1-Nrf2 信号通路方面也最有效（浓度 <3 μ M 时诱导五倍）。在评估抗增殖活性的七种化合物中，3k 和 3r 的活性最高，

  DOI：

  10.1002/ejoc.201501278

文献信息

• Chromenone derivatives useful for the treatment of neurodegenerative diseases
  申请人：AxoGlia Therapeutics S.A.

  公开号：EP2112145A1

  公开（公告）日：2009-10-28

  Compounds of general formula (I) and (II) in which R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14 and R15 have the meanings given in the specification, are useful in the treatment of neurodegenerative disease.

  通式（I）和（II）的化合物 其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、R13、R14和R15具有规范中给定的含义，在神经退行性疾病的治疗中是有用的。
• Flavonoids with M1 Muscarinic Acetylcholine Receptor Binding Activity
  作者：Meyyammai Swaminathan、Chin Chee、Sek Chin、Michael Buckle、Noorsaadah Rahman、Stephen Doughty、Lip Chung

  DOI：10.3390/molecules19078933

  日期：——

  Muscarinic acetylcholine receptor-active compounds have potential for the treatment of Alzheimer’s disease. In this study, a series of natural and synthetic flavones and flavonols was assayed in vitro for their ability to inhibit radioligand binding at human cloned M1 muscarinic receptors. Several compounds were found to possess competitive binding affinity (Ki = 40–110 µM), comparable to that of acetylcholine (Ki = 59 µM). Despite the fact that these compounds lack a positively-charged ammonium group under physiological conditions, molecular modelling studies suggested that they bind to the orthosteric site of the receptor, mainly through non-polar interactions.

  毒蕈碱乙酰胆碱受体活性化合物具有治疗阿尔茨海默病的潜力。在这项研究中，对一系列天然和合成黄酮和黄酮醇进行了体外检测，以确定它们抑制人体克隆 M1 肌卡因受体的放射性配体结合的能力。结果发现，有几种化合物具有竞争性结合亲和力（Ki = 40-110 µM），与乙酰胆碱（Ki = 59 µM）的结合亲和力相当。尽管这些化合物在生理条件下缺乏带正电荷的铵基团，但分子建模研究表明，它们主要通过非极性相互作用与受体的正交位点结合。
• CHROMENONE DERIVATIVES USEFUL FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
  申请人：Coowar Djalil

  公开号：US20110144194A1

  公开（公告）日：2011-06-16

  Compounds of general formula (I) and (II) in which R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 and R 15 have the meanings given in the specification, are useful in the treatment of neurodegenerative disease.

  通式（I）和（II）的化合物，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、R13、R14和R15的含义如规范中所述，对于治疗神经退行性疾病是有用的。
• Exploring quercetin and luteolin derivatives as antiangiogenic agents
  作者：Divyashree Ravishankar、Kimberly A. Watson、Samuel Y. Boateng、Rebecca J. Green、Francesca Greco、Helen M.I. Osborn

  DOI：10.1016/j.ejmech.2015.04.056

  日期：2015.6

  The formation of new blood vessels from the pre-existing vasculature (angiogenesis) is a crucial stage in cancer progression and, indeed, angiogenesis inhibitors are now used as anticancer agents, clinically. Here we have explored the potential of flavonoid derivatives as antiangiogenic agents. Specifically, we have synthesised methoxy and 4-thio derivatives of the natural flavones quercetin and luteolin, two of which (4-thio quercetin and 4-thio luteolin) had never been previously reported. Seven of these compounds showed significant (p < 0.05) antiangiogenic activity in an in vitro scratch assay. Their activity ranged from an 86% inhibition of the vascular endothelium growth factor (VEGF)-stimulated migration (observed for methoxyquercetin at 10 mu M and for luteolin at 1 mu M) to a 36% inhibition (for thiomethoxy quercetin at 10 mu M). Western blotting studies showed that most (4 out of 7) compounds inhibited phosphorylation of the VEGF receptor-2 (VEGFR2), suggesting that the antiangiogenic activity was due to an interference with the VEGF/VEGFR2 pathway. Molecular modelling studies looking at the affinity of our compounds towards VEGFR and/or VEGF confirmed this hypothesis, and indeed the compound with the highest antiangiogenic activity (methoxyquercetin) showed the highest affinity towards VEGFR and VEGF. As reports from others have suggested that structurally similar compounds can elicit biological responses via a non-specific, promiscuous membrane perturbation, potential interactions of the active compounds with a model lipid bilayer were assessed via DSC. Luteolin and its derivatives did not perturb the model membrane even at concentrations 10 times higher than the biologically active concentration and only subtle interactions were observed for quercetin and its derivatives. Finally, cytotoxicity assessment of these flavonoid derivatives against MCF-7 breast cancer cells demonstrated also a direct anticancer activity albeit at generally higher concentrations than those required for an antiangiogenic effect (10 fold higher for the methoxy analogues). Taken together these results show promise for flavonoid derivatives as antiangiogenic agents. (C) 2015 Elsevier Masson SAS. All rights reserved.
• [EN] CHROMENONE DERIVATIVES USEFUL FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] DÉRIVÉS DE CHROMÉNONE UTILES POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：AXOGLIA THERAPEUTICS S A

  公开号：WO2009130253A1

  公开（公告）日：2009-10-29

  Compounds of general formula (I) and (II) in which R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14 and R15 have the meanings given in the specification, are useful in the treatment of neurodegenerative disease.