5,6,7-trihydroxy-8-((4-hydroxypiperidin-1-yl)methyl)-2-phenyl-4H-chromen-4-one | 1334523-98-6

• 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: 5,6,7-trihydroxy-8-((4-hydroxypiperidin-1-yl)methyl)-2-phenyl-4H-chromen-4-one
• 英文别名: 8-hydroxypiperidinylmethyl-baicalein；5,6,7-trihydroxy-8-[(4-hydroxypiperidin-1-yl)methyl]-2-phenylchromen-4-one
• CAS: 1334523-98-6
• 化学式: C₂₁H₂₁NO₆
• 分子量: 383.401
• InChiKey: HERQHVGZVXIZFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  111
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  甲烷磺酸 、 5,6,7-trihydroxy-8-((4-hydroxypiperidin-1-yl)methyl)-2-phenyl-4H-chromen-4-one 以 乙醇 为溶剂， 生成 5,6,7-trihydroxy-8-((4-hydroxypiperidin-1-yl)methyl)-2-phenyl-4H-chromen-4-one mesylate
  参考文献：
  名称：

  CYCLIN-DEPENDENT PROTEIN KINASES INHIBITORS OF SCUTELLARIA FLAVONOID ORGANIC AMINE DERIVATIVES, SYNTHESIS AND USE THEREOF

  摘要：

  本发明提供了一系列依赖于细胞周期蛋白激酶（Cdks）的抑制剂，即黄芩黄酮有机胺衍生物，其合成和使用方法。制备方法如下：以黄芩中的黄芩素（或黄芩苷）为引物化合物，与甲醛溶液和有机胺化合物按摩尔比1:1-1.2:1-1.2混合，加入重量为黄芩素两倍的甲醇，在50-70°C下反应，过滤沉淀并洗涤，然后干燥以得到含量不低于97%（重量）的产品。类似于Flavopiridol和P276-00，黄芩素有机胺衍生物抑制Cdks的活性比黄芩苷增加了50倍。它可以选择性地诱导增殖期癌细胞的凋亡，对正常结构几乎没有影响，属于细胞周期抑制剂类的抗癌药物。该产品具有丰富的原材料来源和简单的工艺，高纯度，低成本，代谢机制清晰，效率高，毒性低，可以与酸盐一起制成口服制剂或注射剂，预计将成为高效低毒的抗癌和艾滋病药物。

  公开号：

  US20100197619A1
• 作为产物：
  描述：

  4-羟基哌啶 、 聚合甲醛 、 黄芩素 以 甲醇 、 水 为溶剂， 反应 8.0h， 生成 5,6,7-trihydroxy-8-((4-hydroxypiperidin-1-yl)methyl)-2-phenyl-4H-chromen-4-one
  参考文献：
  名称：

  设计，合成，生物学评估和新型黄酮类化合物作为H3R抑制剂的分子对接

  摘要：

  设计，合成和评估了一系列新颖的黄酮衍生物的H 3 R抑制活性。结果显示四种化合物显示出显着的抗H 3 R活性。分子对接实验表明，盐桥，氢键和疏水相互作用都促进了抑制剂与H 3 R之间的相互作用。

  DOI：

  10.1111/cbdd.12981

文献信息

• Cyclin-dependent protein kinases inhibitors of Scutellaria flavonoid organic amine derivatives, synthesis and use thereof
  申请人：Zhang Shixuan

  公开号：US08377895B2

  公开（公告）日：2013-02-19

  The present invention provides a series of cyclin-dependent protein kinases (Cdks) inhibitors, Scutellaria flavonoid organic amine derivatives, synthesis and use thereof. The preparation method is as follows: taking Baicalein (or Wogonin) from Scutellaria baicalensis as lead compound, mixting it with formaldehyde solution and organic amine compounds based on the molar ratio of 1:1-1.2:1-1.2, adding methanol of duplicate weight than baicalein and reacting at 50-70° C., filtering the sediment and washing and then drying so as to get the product with a content of not less than 97% (weight). Similar to Flavopiridol and P276-00, the activity of baicalein organic amine derivatives inhibiting Cdks has an increase of 50 times compared with that of Baicalin. It can selectively induce apoptosis of the proliferative phase cancer cells, which has scarcely any influence to the normal structure, and it belongs to anticancer drugs of cell cycle inhibitor kind. The product has a rich source of raw materials and has simple process, high purity, low cost, clear metabolic mechanism, high efficiency and low toxicity, which can be made into oral preparations or injections together with acid salts and is expected to become high efficient and low toxicity anti-cancer and AIDS drugs.

  本发明提供了一系列的细胞周期依赖性蛋白激酶（Cdks）抑制剂，即黄芩素类有机胺衍生物，以及它们的合成和使用方法。该制备方法如下：以黄芩根中的黄芩素（或黄芩苷）为引物化合物，按照摩尔比1:1-1.2:1-1.2的比例，将其与甲醛溶液和有机胺化合物混合，加入比黄芩素重量翻倍的甲醇，在50-70℃下反应，过滤沉淀并洗涤，然后干燥，以获得含量不低于97%（重量）的产品。与黄芩苷相比，类似于Flavopiridol和P276-00，黄芩素有机胺衍生物抑制Cdks的活性增加了50倍。它可以选择性地诱导增殖期癌细胞的凋亡，对正常结构几乎没有影响，属于细胞周期抑制剂类的抗癌药物。该产品原材料来源丰富，工艺简单，纯度高，成本低，代谢机制清晰，效率高，毒性低，可以与酸盐一起制成口服制剂或注射剂，预计成为高效低毒的抗癌和艾滋病药物。
• CDK1 inhibitors of acetyl chrysin mannich base derivatives, synthesis and use thereof
  申请人：Zhang Fan

  公开号：US10471054B2

  公开（公告）日：2019-11-12

  Provided is a series of acetyl Chrysin Mannich base derivatives with the structures illustrated in the following scheme: wherein R1 is acetyl and R2 is cycloalkylamine-methyl, or R2 is acetyl and R1 is cycloalkylamine-methyl. Such derivatives are cyclin-dependent protein kinases 1 (CDK1) selective inhibitors. Base on the levels of .O2− and Fe++ are higher 5-15 times in cancer cells than in normal cells, the action mechanism of such derivatives by regulating intracellular reactive oxygen species (ROS) is activating mitochondria apoptosis pathway without the death receptor pathway, thus selectively inducing apoptosis of cancer cells and protecting normal cells. Inside, CH-j has a good druggability for the selectivity of solid cancers. Moreover, CH-f has also a good druggability for the systemic cancers.

  本研究提供了一系列乙酰基 Chrysin Mannich 碱衍生物，其结构如下图所示：其中 R1 是乙酰基，R2 是环烷基胺甲基，或 R2 是乙酰基，R1 是环烷基胺甲基。这类衍生物是细胞周期蛋白依赖性蛋白激酶 1（CDK1）选择性抑制剂。基于癌细胞中.O2-和Fe++的水平比正常细胞高5-15倍，此类衍生物通过调节细胞内活性氧（ROS）的作用机制是激活线粒体凋亡途径，而不是死亡受体途径，从而选择性地诱导癌细胞凋亡，保护正常细胞。其中，CH-j 对实体瘤的选择性具有良好的可药性。此外，CH-f 对全身性癌症也有良好的可药性。
• CDK1 INHIBITORS OF ACETYL CHRYSIN MANNICH BASE DERIVATIVES, SYNTHESIS AND USE THEREOF
  申请人：ZHANG Fan

  公开号：US20190216792A1

  公开（公告）日：2019-07-18

  Provided is a series of acetyl Chrysin Mannich base derivatives with the structures illustrated in the following scheme: wherein R 1 is acetyl and R 2 is cycloalkylamine-methyl, or R 2 is acetyl and R 1 is cycloalkylamine-methyl. Such derivatives are cyclin-dependent protein kinases 1 (CDK1) selective inhibitors. Base on the levels of .O 2 − and Fe ++ are higher 5-15 times in cancer cells than in normal cells, the action mechanism of such derivatives by regulating intracellular reactive oxygen species (ROS) is activating mitochondria apoptosis pathway without the death receptor pathway, thus selectively inducing apoptosis of cancer cells and protecting normal cells. Inside, CH-j has a good druggability for the selectivity of solid cancers. Moreover, CH-f has also a good druggability for the systemic cancers.
• US8377895B2
  申请人：——

  公开号：US8377895B2

  公开（公告）日：2013-02-19