(Z)-2-(3,4-dimethoxybenzylidene)-6-hydroxybenzofuran-3(2H)-one | 32396-83-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 橙酮类黄酮
• 英文名称: (Z)-2-(3,4-dimethoxybenzylidene)-6-hydroxybenzofuran-3(2H)-one
• 英文别名: (Z)-6-hydroxy-2-(3,4-dimethoxybenzylidene)benzofuran-3(2H)-one；6-hydroxy-3',4'-dimethoxy-2-(phenylmethylene)-3(2H)-benzofuranone；(2Z)-2-(3,4-dimethoxybenzylidene)-6-hydroxy-1-benzofuran-3(2H)-one；(2Z)-2-[(3,4-dimethoxyphenyl)methylidene]-6-hydroxy-1-benzofuran-3-one
• CAS: 32396-83-1
• 化学式: C₁₇H₁₄O₅
• mdl: MFCD04144859
• 分子量: 298.295
• InChiKey: YUCCNWHJQXNUQE-PXNMLYILSA-N

物化性质

• 沸点：
  531.2±50.0 °C(Predicted)
• 密度：
  1.354±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.117
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (Z)-2-(3,4-dimethoxybenzylidene)-6-hydroxybenzofuran-3(2H)-one 在 potassium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (Z)-2-(3,4-dimethoxybenzylidene)-6-(5-(piperidin-1-yl)pentoxy)benzofuran-3(2H)-one hydrochloride
  参考文献：
  名称：

  Synthesis of aminoalkyl-substituted aurone derivatives as acetylcholinesterase inhibitors

  摘要：

  Alzheimer's disease (AD), a progressive and neurodegenerative disorder of the brain, is the most common cause of dementia among elderly people. To date, the successful therapeutic strategy to treat AD is maintaining the levels of acetylcholine by inhibiting acetylcholinesterase (AChE). In the present study, aurone derivatives were designed and synthesized as AChE inhibitors based on the lead structure of sulfuretin. Of those synthesized, compound 10d showed ca. 1700-fold and 6-fold higher AChE inhibitory activity than sulfuretin and galantamine, respectively. This compound also ameliorated scopolamine-induced memory deficit in mice when administered orally at the dose of 1 and 2 mg/kg. (C) 2014 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.11.004
• 作为产物：
  描述：

  2-氯-1-(2,4-二羟基苯基)乙酮 在 盐酸 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 异丙醇 为溶剂， 反应 24.0h， 生成 (Z)-2-(3,4-dimethoxybenzylidene)-6-hydroxybenzofuran-3(2H)-one
  参考文献：
  名称：

  设计和合成一类具有抗氧化特性的新型 PDE4 抑制剂作为潜在治疗 COPD 的双功能药物

  摘要：

  众所周知，慢性阻塞性肺疾病（COPD）患者总是陷入炎症和氧化应激的恶性循环中，因此抗炎和抗氧化双功能药物可能会打断COPD的这种恶性循环。磷酸二酯酶 4 (PDE4) 抑制剂作为抗炎药，已在临床上用于 COPD 治疗，具有抗氧化特性的 PDE4 抑制剂可能是设计双功能 COPD 药物的良好策略。Sappanone A 是我们在之前的研究中从天然产物中鉴定出的第一个具有抗氧化特性的 PDE4 抑制剂，在本研究中我们将其作为命中化合物来设计用于 COPD 的新型双功能药物。27种sappanone A的衍生物，包括同型异黄酮，创新性地融合多酚类儿茶酚的抗氧化药效团和咯利普兰、罗氟司特、阿普司特等儿茶酚醚类PDE4抑制剂提取的儿茶酚醚药效团，创新设计合成了橙酮类和查耳酮类化合物。对所有化合物进行了 PDE4 抑制和自由基清除对 2, 2-二苯基-1-苦基肼 (DPPH) 活性的体外测定。在此我们获得了一系列双功能化合物，其

  DOI：

  10.1016/j.ejmech.2023.115374

文献信息

• Benzofuranone derivatives and a method for producing them
  申请人：Snow Brand Milk Products Co., Ltd.

  公开号：US06143779A1

  公开（公告）日：2000-11-07

  The present invention provides new benzofuranone derivatives and a method for producing the derivatives useful for a therapeutic agent for preventing and/or treating hormone dependent diseases. The present invention is a new benzofuranone derivative represented by a particular general formula (I). ##STR1## In the production, a particular benzofuranone compound and a particular benzaldehyde are reacted.

  本发明提供了新的苯并呋喃酮衍生物以及用于生产这些衍生物的方法，该方法对于预防和/或治疗激素依赖性疾病的治疗剂非常有用。本发明是由特定通式（I）表示的新苯并呋喃酮衍生物。在生产过程中，特定的苯并呋喃酮化合物和特定的苯甲醛进行反应。
• Synthesis of Flavonoid Derivatives of Cytisine. 5. Aminomethylation of 6-Hydroxyaurones
  作者：A. V. Popova、S. P. Bondarenko、E. V. Podobii、M. S. Frasinyuk、V. I. Vinogradova

  DOI：10.1007/s10600-017-2096-y

  日期：2017.7

  Aminomethylation of 6-hydroxy- and 6-hydroxy-7-methylaurones by the alkaloid cytisine was studied. It was shown that the aminomethylation of the 6-hydroxyaurones occurred at the 7-position of the benzofuran ring and at the 5-position if the 7-position was occupied.

  研究了生物碱金雀花碱对6-羟基和6-羟基-7-甲基香豆酮进行氨基甲基化的反应。结果表明，6-羟基香豆酮的氨基甲基化发生在苯并呋喃环的7位上，如果7位已被占据，则发生在5位上。
• Efficient synthesis of aurone Mannich bases and evaluation of their antineoplastic activity in PC-3 prostate cancer cells
  作者：Antonina V. Popova、Mykhaylo S. Frasinyuk、Svitlana P. Bondarenko、Wen Zhang、Yanqi Xie、Zachary M. Martin、Xianfeng Cai、Michael V. Fiandalo、James L. Mohler、Chunming Liu、David S. Watt、Vitaliy M. Sviripa

  DOI：10.1007/s11696-018-0485-8

  日期：2018.10

  acetoxymethyl and methoxymethyl derivatives of 6-hydroxyaurones, some of which showed promising inhibition of PC-3 prostate cancer cell proliferation in the high nanomolar to low micromolar range that exceeded that of cisplatin. Graphical abstractCompound 12c (R3 = Ac, Ar = 3,4-OMePh) displays 75% inhibition of PC-3 prostate cancer cells proliferation at 300 nM concentration.

  摘要使用由二甲胺、二丙胺、双(2-甲氧基乙基)胺、N-甲基丁胺、 N-甲基苄胺、吗啉制备的缩醛胺，通过N,N-二烷基氨基甲基化，实现了区域选择性合成 6-羟基金黄酮的 C-7 曼尼希碱的有效方法、哌啶和1-甲基哌嗪。这些金黄酮中 7-( N,N-二烷基氨基)甲基基团的进一步转化导致 6-羟基金黄酮的 C-7 乙酰氧基甲基和甲氧基甲基衍生物的形成，其中一些在高浓度时显示出对 PC-3 前列腺癌细胞增殖的有希望的抑制作用。超过顺铂的纳摩尔到低微摩尔范围。 图形概要Compound 12c (R 3 = Ac, Ar = 3,4-OMePh) 在 300 nM 浓度下对 PC-3 前列腺癌细胞增殖有 75% 的抑制作用。
• New Heterocyclic Pyrano[2′,3′:5,6]Chromeno[3,2-c]Pyridin-4-Ones and Furo[2′,3′:5,6]Chromeno[3,2-c]Pyridin-3(2H)-Ones Synthesized Via a Hetero-Diels–Alder Reaction
  作者：A. V. Popova、G. P. Mrug、K. M. Kondratyuk、S. P. Bondarenko、M. S. Frasinyuk

  DOI：10.1007/s10600-016-1846-6

  日期：2016.11

  hetero-Diels–Alder reactions was studied. Isoflavones and aurones were used as examples to show that their Mannich bases reacted with 4-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)morpholine through an elimination mechanism and subsequent cycloaddition to form derivatives of the new heterocyclic systems pyrano[2′,3′:5,6]chromeno[3,2-c]pyridin-4-one and furo[2′,3′:5,6]chromeno[3,2-c]pyridin-3(2H)-one.

  研究了类黄酮曼尼希碱在逆电子需求异质 Diels-Alder 反应中的行为。以异黄酮和金酮为例，表明它们的曼尼希碱与 4-(1-甲基-1,2,3,6-四氢吡啶-4-基)吗啉通过消除机制和随后的环加成反应形成新的衍生物杂环系统 pyrano[2',3':5,6]chromeno[3,2-c]pyridin-4-one 和 furo[2',3':5,6]chromeno[3,2-c]pyridin- 3(2H)-一。
• Drug Design, Synthesis and In Vitro Evaluation of Substituted Benzofurans as Hsp90 Inhibitors
  作者：Sundeep Kadasi、Thadeu E.M.M. Costa、Neha Arukala、Mallika Toshakani、Chaitanya Duggineti、Sreekanth Thota、Sayan D. Gupta、Shiva Raj、Carmen Penido、Maria G. Henriques、Nulgumnalli M. Raghavendra

  DOI：10.2174/1573406413666170623085534

  日期：2018.1.11

  Background: Heat shock protein 90 is a molecular chaperone required for the stability and function of several client proteins that promote cancer cell growth and/or survival. Discovery of Hsp90 inhibitors has emerged as an attractive target of research in cancer therapeutics. Natural products like geldanamycin and radicicol are established Hsp90 inhibitors, but face limitations with toxicity and inactivity, by in vivo studies respectively. However, they lay the logical starting point for the design of novel synthetic or semi-synthetic congeners as Hsp90 inhibitors. Objective: In this article, the structure based drug design of substituted 2-aryl/heteroarylidene-6- hydroxybenzofuran-3(2H)-one analogues to optimize and mimic the pharmacophoric interactions of the valid Hsp90 inhibitor radicicolis focused. Method: In silico docking study was performed by Surflex dock-Geom (SYBYL- X 1.2 drug discovery suite) and the designed ligands were chemically synthesized by conventional method using resorcinol and chlororesorcinol as starting materials. Two dimensional chemical similarity search was carried out to identify the chemical space of ‘SY' series in comparison with reported Hsp90 inhibitors. The in vitro cell proliferation assay (resazurin reduction method) and proteomic investigation (DARTS) was carried out on whole cell lysate to evaluate anticancer activity. Results: The chemical structures of all the synthesized compounds were confirmed by IR, 1H-NMR and Mass spectral analysis. The results of chemical similarity search show that SY series fit it in the chemical space defined by existing Hsp90 inhibitors. In vitro cell proliferation assay, against human melanoma and breast cancer cell lines, identified ‘SY3' as the promising anticancer agent amongst the series. Conclusion: Docking studies, 2D chemical similarity search, resazurin reduction assay and qualitative proteomic analysis identify ‘SY3’as a promising Hsp90 inhibitor amongst the series.

  背景：热休克蛋白90是一种分子伴侣，参与多种促进癌细胞生长和/或存活的目标蛋白的稳定性和功能。Hsp90抑制剂的发现已成为癌症治疗研究中的一个有吸引力的目标。天然产物如胶丹霉素和雷地西酮已被确立为Hsp90抑制剂，但在体内研究中面临着毒性和无活性等限制。然而，它们为设计新型合成或半合成的相关化合物作为Hsp90抑制剂奠定了逻辑起点。 目标：本文聚焦于取代的2-芳基/杂芳基-6-羟基苯并呋喃-3(2H)-酮类似物的结构基础药物设计，以优化和模拟有效Hsp90抑制剂雷地西酮的药效团相互作用。 方法：通过Surflex dock-Geom (SYBYL-X 1.2药物发现套件)进行虚拟对接研究，设计的配体通过传统方法合成，使用对苯二酚和氯对苯二酚作为起始材料。进行二维化学相似性搜索，以识别与已报道Hsp90抑制剂相比的'SY'系列化学空间。采用体外细胞增殖测定（重氮还原法）和蛋白质组学研究（DARTS）对全细胞裂解液进行评估，以评估抗癌活性。 结果：所有合成化合物的化学结构通过红外光谱、1H-NMR和质谱分析得到确认。化学相似性搜索的结果表明，SY系列符合现有Hsp90抑制剂所定义的化学空间。在针对人黑色素瘤和乳腺癌细胞系的体外细胞增殖测定中，'SY3'被识别为该系列中有前景的抗癌剂。 结论：对接研究、二维化学相似性搜索、重氮还原测定和定性蛋白组学分析都确认了'SY3'作为该系列中有前景的Hsp90抑制剂。