2-(3,4-bis(methoxymethoxy)phenyl)-5-hydroxy-3,7-bis(methoxymethoxy)-4H-chromen-4-one | 143724-67-8

• 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: 2-(3,4-bis(methoxymethoxy)phenyl)-5-hydroxy-3,7-bis(methoxymethoxy)-4H-chromen-4-one
• 英文别名: Quercetin 3,3',4',7-tetra(methoxymethy) ether；2-[3,4-bis(methoxymethoxy)phenyl]-5-hydroxy-3,7-bis(methoxymethoxy)chromen-4-one
• CAS: 143724-67-8
• 化学式: C₂₃H₂₆O₁₁
• 分子量: 478.453
• InChiKey: PQDLPSCRBYSFMO-UHFFFAOYSA-N

物化性质

• 沸点：
  665.7±55.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  34
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  2-(3,4-bis(methoxymethoxy)phenyl)-5-hydroxy-3,7-bis(methoxymethoxy)-4H-chromen-4-one 在 盐酸 、 florisil 、 potassium carbonate 作用下， 以 甲醇 、 水 、 丙酮 、 甲苯 为溶剂， 反应 18.5h， 生成 3,3',4',7-tetramethoxy-8-C-prenylquercetin
  参考文献：
  名称：

  的区域选择性合成Ç -prenylated黄酮经由分子内[1,3]或[1,5]变换反应通过酸性粘土催化

  摘要：

  异戊二烯侧链和二氢吡喃基骨架存在于许多天然和合成的生物活性类黄酮中。用于合成一个高效和区域选择性方法Ç -prenylated黄酮经由分子内[1,3]或[1,5]移位5-反应ö -prenylflavonoids通过硅酸镁载体或蒙脱土催化进行说明。Florisil催化5- O-异戊烯基类黄酮的分子内[1,5]转化反应，从而获得8 - C-异戊烯基化黄酮，蒙脱土K10表现出优异的选择性，可促进分子内[1,3]转化反应获得6- C。-异戊二烯黄酮与Florisil和Montmorillonite KSF的比较。该方法提供了在温和条件下使用市售和廉价的催化剂以高收率选择性选择性地生物合成重要的生物学上重要的C-戊烯基黄酮类化合物的实用方法。

  DOI：

  10.1016/j.tetlet.2019.151138
• 作为产物：
  描述：

  芦丁 在 盐酸 、 硫酸 、 sodium hydride 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 2-(3,4-bis(methoxymethoxy)phenyl)-5-hydroxy-3,7-bis(methoxymethoxy)-4H-chromen-4-one
  参考文献：
  名称：

  大金钱草提取物和类黄酮的降血糖和降血脂双重活性和最有效的8-异戊二烯槲皮素的有效合成

  摘要：

  由于糖脂代谢紊乱往往是单靶点治疗无法控制血糖和血脂水平等并发症，因此寻找新的潜在药物或功能性食品作用于多靶点已迫在眉睫。大金钱草根茎叶的降糖降血脂双重作用, 用于中药, 进行了评价。制备了 12 种不同提取条件的提取物，发现提取物 9 对果糖 1、6-双磷酸酶 (FBPase)、α-葡萄糖苷酶和胰脂肪酶具有潜在的抑制活性，并促进细胞葡萄糖消耗并降低细胞内脂质含量. 从提取物 9 中分离鉴定出 5 种黄酮类化合物，其中 8-异戊二烯槲皮素表现出强效的 α-葡萄糖苷酶 (IC 50  = 4.38 μM) 和 FBPase (IC 50  = 3.62 μM) 双重抑制活性，比阿卡波糖 (IC) 高 75 倍。50  = 330.10 μM)，与 AMP (IC 50 = 2.92 微米）。此外，8-异戊二烯槲皮素能够促进葡萄糖消耗并降低脂质含量。此外，以廉价、市售的芦丁为原料，通过6个步骤高

  DOI：

  10.1016/j.fitote.2021.105083

文献信息

• [EN] ALLOSTERIC MODULATORS OF FACTOR XIa AS ANTICOAGULANT AGENTS<br/>[FR] MODULATEURS ALLOSTÉRIQUES DE FACTEUR XIA EN TANT QU'AGENTS ANTICOAGULANTS
  申请人：UNIV VIRGINIA COMMONWEALTH

  公开号：WO2014075045A1

  公开（公告）日：2014-05-15

  Compounds which allosterically modulate and/or inhibit factor XIa activity are provided, as are methods of their use. These compounds include i) sulfated gallolyl glucosides, ii) sulfated quinazolinones, and iii) sulfated inositol analogs. The compounds used as anticoagulant agents.

  提供了能够以别构调节和/或抑制XIa因子活性的化合物，以及它们的使用方法。这些化合物包括i) 硫酸酯化没食子醇葡萄糖苷，ii) 硫酸酯化喹唑啉酮，和iii) 硫酸酯化肌醇类似物。这些化合物被用作抗凝剂。
• Plasmin Regulation through Allosteric, Sulfated, Small Molecules
  作者：Rami Al-Horani、Rajesh Karuturi、Domonique White、Umesh Desai

  DOI：10.3390/molecules20010608

  日期：——

  matrix remodeling. Heparin, a natural polydisperse sulfated glycosaminoglycan, is known to allosterically modulate plasmin activity. No small allosteric inhibitor of plasmin has been discovered to date. We screened an in-house library of 55 sulfated, small glycosaminoglycan mimetics based on nine distinct scaffolds and varying number and positions of sulfate groups to discover several promising hits. Of

  纤溶酶是一种关键的丝氨酸蛋白酶，在血块溶解和细胞外基质重塑中起主要作用。肝素是一种天然的多分散的硫酸化糖胺聚糖，已知会变构地调节纤溶酶的活性。迄今为止，尚未发现纤溶酶的变构抑制剂。我们基于9个不同的支架以及不同数量和位置的硫酸盐基团，筛选了55个硫酸化的小糖胺聚糖模拟物的内部库，以发现一些有前途的命中。其中，发现五硫酸化的类黄酮-喹唑啉酮二聚体32是最有效的硫酸化纤溶酶小抑制剂（IC50 = 45μM，功效= 100％）。Michaelis-Menten动力学研究表明，这些抑制剂对纤溶酶具有变构抑制作用。研究还表明，最有效的抑制剂对纤溶酶的选择性优于凝血酶和Xa因子，两种丝氨酸蛋白酶在凝血级联反应中 有趣的是，不同的抑制剂表现出不同的功效水平（40％-100％），这一观察结果暗示了变构过程提供的独特优势。总体而言，我们的工作提出了首个小型的合成别构纤溶酶抑制剂，用于进一步的合理设计。
• SULFATED AND UNSULFATED FLAVONOID OLIGOMERS AS CANCER THERAPEUTICS
  申请人：VIRGINIA COMMONWEALTH UNIVERSITY

  公开号：US20160280676A1

  公开（公告）日：2016-09-29

  Sulfated and unsulfated flavonoid oligomers as inhibitors of cancer stem cells (CSCs) are provided. In particular, sulfated flavonoid dimers are shown to selectively inhibit CSCs growth and self-renewal both in vitro and in vivo.

  提供了硫酸化和非硫酸化黄酮寡聚体作为癌症干细胞(CSCs)抑制剂。特别是，硫酸化黄酮二聚体在体内外均显示出选择性抑制CSCs的生长和自我更新的作用。
• Studies on fragment-based design of allosteric inhibitors of human factor XIa
  作者：Rio S. Boothello、Nehru Viji Sankaranarayanan、Daniel K. Afosah、Rajesh Karuturi、Rami A. Al-Horani、Umesh R. Desai

  DOI：10.1016/j.bmc.2020.115762

  日期：2020.12

  Human factor XIa (hFXIa) has emerged as an attractive target for development of new anticoagulants that promise higher level of safety. Different strategies have been adopted so far for the design of anti-hFXIa molecules including competitive and non-competitive inhibition. Of these, allosteric dysfunction of hFXIa's active site is especially promising because of the possibility of controlled reduction in activity that may offer a route to safer anticoagulants. In this work, we assess fragment-based design approach to realize a group of novel allosteric hFXIa inhibitors. Starting with our earlier discovery that sulfated quinazolinone (QAO) bind in the heparin-binding site of hFXIa, we developed a group of two dozen dimeric sulfated QAOs with intervening linkers that displayed a progressive variation in inhibition potency. In direct opposition to the traditional wisdom, increasing linker flexibility led to higher potency, which could be explained by computational studies. Sulfated QAO 19S was identified as the most potent and selective inhibitor of hFXIa. Enzyme inhibition studies revealed that 19S utilizes a non-competitive mechanism of action, which was supported by fluorescence studies showing a classic sigmoidal binding profile. Studies with selected mutants of hFXIa indicated that sulfated QAOs bind in heparin-binding site of the catalytic domain of hFXIa. Overall, the approach of fragment-based design offers considerable promise for designing heparin-binding site-directed allosteric inhibitors of hFXIa.
• Effects of Flavonoids on Cell Proliferation and Caspase Activation in a Human Colonic Cell Line HT29:  An SAR Study
  作者：Jean-Baptiste Daskiewicz、Flore Depeint、Lionel Viornery、Christine Bayet、Geraldine Comte-Sarrazin、Gilles Comte、Jennifer M. Gee、Ian T. Johnson、Karine Ndjoko、Kurt Hostettmann、Denis Barron

  DOI：10.1021/jm040770b

  日期：2005.4.1

  A library of 42 natural and synthetic flavonoids has been screened for their effect on cell proliferation and apoptosis in a human colonic cell line (HT-29). Examples of different classes of flavonoids have been screened, and the effects of hydroxylation, methoxylation and/or C-alkylation at various positions in the A- and B-rings have been assessed. Flavones and flavonols possess greater antiproliferative activity than chalcones and flavanones. With respect to structural modification of flavonoids, C-isoprenylation was by far the most effective, with substitution at the 8-position and longer chains, such as geranyl giving the best results. Finally, most compounds that significantly reduced cell survival also increased caspase activity, suggesting that at least part of their antiproliferative activity might be attributable to an apoptotic response.