2-(4,11-dimethyl-2-oxo-6,7,8,9-tetrahydro-2H-benzo[4,5]furo[3,2-g]chromen-3-yl)acetic acid | 664366-24-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 2-(4,11-dimethyl-2-oxo-6,7,8,9-tetrahydro-2H-benzo[4,5]furo[3,2-g]chromen-3-yl)acetic acid
• 英文别名: (4',11'-dimethyl-2'-oxo-6',7',8',9'-tetrahydrobenzofuro[3,2-g]-1-benzopyran-3'-yl)acetic acid；(4,11-dimethyl-2-oxo-6,7,8,9-tetrahydro-2H-[1]benzofuro[3,2-g]chromen-3-yl)acetic acid；2-(4,11-dimethyl-2-oxo-6,7,8,9-tetrahydro-[1]benzofuro[3,2-g]chromen-3-yl)acetic acid
• CAS: 664366-24-9
• 化学式: C₁₉H₁₈O₅
• mdl: MFCD03850089
• 分子量: 326.349
• InChiKey: FWJCITRYQDXYPE-UHFFFAOYSA-N

物化性质

• 沸点：
  565.1±50.0 °C(Predicted)
• 密度：
  1.330±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  76.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4,11-dimethyl-2-oxo-6,7,8,9-tetrahydro-2H-benzo[4,5]furo[3,2-g]chromen-3-yl)acetic acid 在 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 生成 2-(4,11-dimethyl-2-oxo-6,7,8,9-tetrahydro-[1]benzofuro[3,2-g]chromen-3-yl)-N-(4-hydroxyphenyl)acetamide
  参考文献：
  名称：

  Psoralen Derivatives as Inhibitors of NF-κB/DNA Interaction: Synthesis, Molecular Modeling, 3D-QSAR, and Biological Evaluation

  摘要：

  Some new psoralen derivatives were synthesized and evaluated as inhibitors of NF-kappa B/DNA interaction, with the aim to investigate the structural determinants required to inhibit this interaction. Starting from molecular docking studies, several possible protein binding sites were proposed and several three-dimensional quantitative structure activity relationship (3D-QSAR) models were built using the docked poses of 29 (the most active psoralen in the series) as templates for alignment of the inhibitors. The selected best model was validated through the prediction of the activity of 17 novel compounds. All the experimental data agreed with the computational experiments, supporting the reliability of the computational approach. The hypothesis about the interaction with NF-kappa B was also supported by surface plasmon resonance based assays using compound 29. All the collected data allowed the identification of compound 29 as a potential candidate for the development of pharmaceutical strategies against the inflammatory phenotype of cystic fibrosis.

  DOI：

  10.1021/jm3009647
• 作为产物：
  描述：

  2,6-二羟基甲苯 在 盐酸 、 sodium hydroxide 、 potassium carbonate 作用下， 以 甲醇 、 异丙醇 、 丙酮 为溶剂， 反应 3.0h， 生成 2-(4,11-dimethyl-2-oxo-6,7,8,9-tetrahydro-2H-benzo[4,5]furo[3,2-g]chromen-3-yl)acetic acid
  参考文献：
  名称：

  摘要：

  Substituted 2-(7-oxofuro[3,2-g]chromen-6-yl) acetic acids, modified psoralen analogs, were synthesized by linear fusion of a furan ring to the coumarin system.

  DOI：

  10.1023/a:1025466317733

文献信息

• Photobiological properties of 3-psoralenacetic acids
  作者：Lisa Dalla Via、Giovanni Marzaro、Alessandra Mazzoli、Adriana Chilin、Giorgia Miolo

  DOI：10.1039/c5pp00210a

  日期：2015.11

  peculiar mechanism of action consisting of a decarboxylation step before exerting their photobiological activity. The most active compound 2 is able to induce a noteworthy photocytotoxic effect, with GI50 values being submicromolar on human tumor cell lines and no effect in the dark. The involvement of DNA photoaddition after UVA light-mediated decarboxylation and ROS formation is responsible for its biological

  合成并研究了一些4,8-二甲基-3-补骨脂乙酸。所有设计的补骨脂酸在呋喃环上带有烷基或环烷基取代基。这些补骨脂素乙酸被证明是一类新型的补骨脂素衍生物，其特征在于有趣的光生物学特性。在3位的羧基可用于赋予亲水性，这似乎不利于经典的插入DNA，这可能是由于与大分子负表面的排斥性相互作用。然而，由于新的衍生物具有独特的作用机理，该特殊的作用机理包括在发挥其光生物活性之前进行的脱羧步骤，因此它们具有显着的光抗增殖活性。活性最高的化合物2能够诱导显着的光细胞毒性作用，GI 50值对人肿瘤细胞系具有亚微摩尔浓度，而在黑暗中则无作用。UVA光介导的脱羧和ROS形成后DNA光加成的参与为其生物学活性负责，如比较脱羧类似物的活性谱所证明。但是，其他生物靶标似乎也参与了光氧化损伤，例如蛋白质。因此，化合物2可以被视为前药，在没有UVA光的情况下没有活性，但在特定的辐射下被激活，从而防止了非选择性的副作用，并为光化学疗法中有用的药物开辟了新的前景。
• Modified coumarins. 20. Furocoumarin derivatives of cytisine
  作者：M. V. Veselovskaya、M. M. Garazd、V. I. Vinogradova、V. P. Khilya

  DOI：10.1007/s10600-006-0098-2

  日期：2006.5

  Cytisine derivatives modified by furocoumarins were synthesized using activated esters.

  使用活化酯合成了呋喃香豆素修饰的金雀花碱衍生物。
• ——
  作者：I. V. Nagorichna、I. P. Dubovik、M. M. Garazd、V. P. Khilya

  DOI：10.1023/a:1025466317733

  日期：——

  Substituted 2-(7-oxofuro[3,2-g]chromen-6-yl) acetic acids, modified psoralen analogs, were synthesized by linear fusion of a furan ring to the coumarin system.
• Psoralen Derivatives as Inhibitors of NF-κB/DNA Interaction: Synthesis, Molecular Modeling, 3D-QSAR, and Biological Evaluation
  作者：Giovanni Marzaro、Adriano Guiotto、Monica Borgatti、Alessia Finotti、Roberto Gambari、Giulia Breveglieri、Adriana Chilin

  DOI：10.1021/jm3009647

  日期：2013.3.14

  Some new psoralen derivatives were synthesized and evaluated as inhibitors of NF-kappa B/DNA interaction, with the aim to investigate the structural determinants required to inhibit this interaction. Starting from molecular docking studies, several possible protein binding sites were proposed and several three-dimensional quantitative structure activity relationship (3D-QSAR) models were built using the docked poses of 29 (the most active psoralen in the series) as templates for alignment of the inhibitors. The selected best model was validated through the prediction of the activity of 17 novel compounds. All the experimental data agreed with the computational experiments, supporting the reliability of the computational approach. The hypothesis about the interaction with NF-kappa B was also supported by surface plasmon resonance based assays using compound 29. All the collected data allowed the identification of compound 29 as a potential candidate for the development of pharmaceutical strategies against the inflammatory phenotype of cystic fibrosis.