5,6,7-trihydroxy-8-((4-methylpiperazin-1-yl)methyl)-2-phenyl-4H-chromen-4-one | 1060171-92-7

• 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-methylpiperazin-1-yl)methyl)-2-phenyl-4H-chromen-4-one
• 英文别名: 5,6,7-trihydroxy-8-[(4-methylpiperazin-1-yl)methyl]-2-phenylchromen-4-one
• CAS: 1060171-92-7
• 化学式: C₂₁H₂₂N₂O₅
• 分子量: 382.416
• InChiKey: NZDRFIGSZYJEPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 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：
  93.5
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  甲基丙烯酸 、 5,6,7-trihydroxy-8-((4-methylpiperazin-1-yl)methyl)-2-phenyl-4H-chromen-4-one 在 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 4-二甲氨基吡啶 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 22.0h， 以40.3%的产率得到5,6-dihydroxy-8-((4-methylpiperazin-1-yl)methyl)-4-oxo-2-phenyl-4H-chromen-7-yl methacrylate
  参考文献：
  名称：

  7-酯-8-氨基亚甲基取代黄芩素衍生物的合成与结构确认

  摘要：

  12 种黄芩素衍生物，由 7-酯和 8-氨基亚甲基衍生，合成为细胞周期蛋白依赖性激酶 1 (CDK1) 抑制剂，通过将四种仲胺之一添加到 C-8，使用曼尼希反应，然后单- 与三种羧酸中的一种进行酯化。通过1 H-、13 C-NMR 和 HMBC 光谱的分析以及化学测试证实，酯化发生在黄芩素的 7-酚羟基位置，而不是发生在 5-或 6-位。

  DOI：

  10.1002/jccs.202100194
• 作为产物：
  描述：

  黄芩苷 在 硫酸 作用下， 以 甲醇 、 水 为溶剂， 反应 0.08h， 生成 5,6,7-trihydroxy-8-((4-methylpiperazin-1-yl)methyl)-2-phenyl-4H-chromen-4-one
  参考文献：
  名称：

  一种黄酮类衍生物及其制备方法和鉴定方法

  摘要：

  本发明公开了一种黄酮类衍生物，所述衍生物结构式包括如通式(Ⅰ)和通式(Ⅱ)所示：其中，R1为烷基或环烷基，R2为烷基或环烷基，R1、R2和氮原子形成脂肪环或者杂环，R3为烷基、芳基或芳烷基，n取值为1～10。本发明还公开了一种黄酮类衍生物的制备方法和鉴定方法。

  公开号：

  CN109265424B

文献信息

• Design, synthesis, and primary activity assays of baicalein derivatives as cyclin‐dependent kinase 1 inhibitors
  作者：Jiajia Mou、Shuang Qiu、Danghui Chen、Yanru Deng、Teka Tekleab

  DOI：10.1111/cbdd.13917

  日期：2021.10

  cyclin-dependent kinase 1 (CDK1) plays an indispensable role in cell cycle regulation, it became an attractive target in rational anti-cancer drug discovery. Herein, we reported a series of baicalein derivatives, which remarkably repressed the proliferation of MCF-7 tumor cells and the activity of CDK1/cyclin B kinase. Among them, compound 4a displayed better inhibition rate than flavopiridol against

  恶性肿瘤是一种死亡率很高的疾病。传统的治疗方法存在副作用、耐药性等诸多弊端。由于细胞周期蛋白依赖性激酶 1 (CDK1) 在细胞周期调节中发挥着不可或缺的作用，因此它成为理性抗癌药物发现的一个有吸引力的目标。在此，我们报道了一系列黄芩素衍生物，它们显着抑制了 MCF-7 肿瘤细胞的增殖和 CDK1/cyclin B 激酶的活性。其中，化合物4a在50 μg/ml浓度下对MCF-7增殖的抑制率优于flavopiridol，与化合物CGP74514A相当，而化合物3o对CDK1/cyclin B激酶的抑制活性最佳（IC 50 = 1.26 微米）。对激酶的抑制活性与抗增殖活性密切相关。分子对接结果表明，化合物3o可以像黄酮吡啶一样通过氢键与 CDK1 的关键氨基酸残基 E81、L83 和 D146 相互作用。并且它还可以通过其引入的7-丙烯酸酯基团与D146形成额外的氢键，这是黄酮吡啶所没有的
• Nitrogen-containing flavonoid analogues as CDK1/cyclin B inhibitors: Synthesis, SAR analysis, and biological activity
  作者：Shixuan Zhang、Jigang Ma、Yongming Bao、Puwen Yang、Liang Zou、Kangjian Li、Xiaodan Sun

  DOI：10.1016/j.bmc.2008.06.055

  日期：2008.8

  A series of nitrogen-containing flavonoid analogues were designed and synthesized by Mannich reaction, and screened for the inhibitory activities of cyclin-dependent kinases using a FRET-based biochemical assay method. The results showed that C-8 nitrogen-containing baicalein analogues 3a-3f exhibited potent CDK1/Cyclin B inhibitory activities. 5,6,7-Trihydroxy-8-(dimethylaminomethyl)-2-phenyl-4H-chromen-4-one

  通过曼尼希反应设计和合成了一系列含氮类黄酮类似物，并使用基于FRET的生化分析方法筛选了细胞周期蛋白依赖性激酶的抑制活性。结果表明，C-8含氮黄ical素类似物3a-3f表现出有效的CDK1 / Cyclin B抑制活性。5,6,7-三羟基-8-（二甲基氨基甲基）-2-苯基-4H-铬n-4-1 3a，5,6,7-三羟基-8-（吡咯烷基甲基）-2-苯基-4H-铬n- 4-one 3b和5,6,7-三羟基-8-（哌啶基甲基）-2-苯基-4H-chromen-4-one 3c（IC（50）1.05-1.28 microM）的效力是黄ical素2的约六倍（IC（50）6.53 microM）。5,6,7-三羟基-8-（吗啉代甲基）-2-苯基-4H-chromen-4-one 3d，5,6,7-三羟基-8-（硫代吗啉代）-2-苯基-4H-chrom en- 4个3e和5,6，
• CYCLIN-DEPENDENT PROTEIN KINASES INHIBITORS OF SCUTELLARIA FLAVONOID ORGANIC AMINE DERIVATIVES, SYNTHESIS AND USE THEREOF
  申请人：Zhang Shixuan

  公开号：US20100197619A1

  公开（公告）日：2010-08-05

  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。
• 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。