2-(3-tert-butyl-5,9-dimethyl-7-oxo-7H-furo[3,2-g]chromen-6-yl)acetic acid

• 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-(3-tert-butyl-5,9-dimethyl-7-oxo-7H-furo[3,2-g]chromen-6-yl)acetic acid
• 英文别名: 4,8-dimethyl-4'-tert-butyl-psoralen-3-acetic acid；(3-tert-butyl-5,9-dimethyl-7-oxo-7H-furo[3,2-g]chromen-6-yl)acetic acid；2-(3-tert-butyl-5,9-dimethyl-7-oxofuro[3,2-g]chromen-6-yl)acetic acid
• 化学式: C₁₉H₂₀O₅
• mdl: MFCD03850700
• 分子量: 328.365
• InChiKey: IZOOUGOSLDMECH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• 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-(3-tert-butyl-5,9-dimethyl-7-oxo-7H-furo[3,2-g]chromen-6-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 4-(2-(3-(tert-butyl)-5,9-dimethyl-7-oxo-7H-furo[3,2-g]chromen-6-yl)acetamido)butanoic acid
  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：

  一氯频呐酮 在 sodium hydroxide 、 potassium carbonate 作用下， 以 异丙醇 、 丙酮 为溶剂， 反应 3.0h， 生成 2-(3-tert-butyl-5,9-dimethyl-7-oxo-7H-furo[3,2-g]chromen-6-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

• Modified Coumarins. 33. Synthesis of Furo- and Dihydropyranocoumarins Containing a Lupinine Moiety
  作者：Yu. A. Nikitina、A. I. Galaev、Ya. L. Garazd、M. M. Garazd、V. G. Kartsev

  DOI：10.1007/s10600-015-1423-4

  日期：2015.9

  New coumarin derivatives containing a lupinine moiety were synthesized via amidation of furocoumarinylacetic, furocoumarinylpropionic, and dihydropyranocoumarinyloxyacetic acids with lupinylamine.

  通过呋喃香豆素乙酸、呋喃香豆素丙酸和二氢吡喃香豆素氧乙酸与羽扇豆胺的酰胺化反应，合成了含有羽扇豆碱分子的新型香豆素衍生物。
• 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。
• Development of a novel furocoumarin derivative inhibiting NF-κB dependent biological functions: Design, synthesis and biological effects
  作者：Monica Borgatti、Adriana Chilin、Laura Piccagli、Ilaria Lampronti、Nicoletta Bianchi、Irene Mancini、Giovanni Marzaro、Francesco dall’Acqua、Adriano Guiotto、Roberto Gambari

  DOI：10.1016/j.ejmech.2011.07.032

  日期：2011.10

  Nuclear Factor kappaB (NF-kappa B) plays a very important role in the control of gene expression and is deeply involved in several human pathologies. Accordingly, molecules targeting NF-kappa B dependent biological functions are considered of great interest. Virtual screening of furocoumarin libraries against NF-kappa B p50 allowed to rank compounds in respect to their expected ability to bind NF-kappa B and the identified compound might be considered for the development of analogs to be tested for biological activity on inhibition of NF-kappa B/DNA complex formation. The data reported in the present paper suggest that, following this approach, the best ranked compounds identified by virtual screening (a) strongly bind in silica to NF-kappa B and (b) efficiently inhibit the molecular interactions between P-32-labeled NF-kappa B double stranded DNA and p50 or p50/p65 complex. These data allowed to develop a novel lead of great interest for inhibiting NF-kappa B dependent biological functions. This novel molecule (compound 2), bearing a methyl group in the 9 position of the psoralen nucleus, exhibits high efficiency in inhibiting NF-kappa B/DNA interactions. In addition, we found that compound 2 is a potent inhibitor of IL-8 gene expression in TNF-alpha treated IB3-1 cystic fibrosis cells. Taken together, our data indicate that compound 2 might find an important place in the set of molecules of interest for the development of pharmaceutical strategies against the inflammatory phenotype of cystic fibrosis. (C) 2011 Elsevier Masson SAS. All rights reserved.
• ——
  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.