methyl 2-[7-(3,3-dimethyl-2-oxobutoxy)-4-methyl-2-oxo-2H-3-chromenyl]acetate | 664365-85-9

• 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: methyl 2-[7-(3,3-dimethyl-2-oxobutoxy)-4-methyl-2-oxo-2H-3-chromenyl]acetate
• 英文别名: methyl [4-methyl-7-(3',3'-dimethyl-2'-oxobutoxy)-2-oxo-2H-benzopyran-3-yl]-acetate；methyl [7-(3,3-dimethyl-2-oxobutoxy)-4-methyl-2-oxo-2H-chromen-3-yl]acetate；methyl 2-[7-(3,3-dimethyl-2-oxobutoxy)-4-methyl-2-oxochromen-3-yl]acetate
• CAS: 664365-85-9
• 化学式: C₁₉H₂₂O₆
• mdl: MFCD03661030
• 分子量: 346.38
• InChiKey: AOBBQNFQVXYECH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-[7-(3,3-dimethyl-2-oxobutoxy)-4-methyl-2-oxo-2H-3-chromenyl]acetate 在 氯化亚砜 、 异丙醇 、 sodium hydroxide 作用下， 反应 4.0h， 生成 L-2-[2'-(3''-tert-butyl-5''-methyl-7''-oxo-7H-furo[3,2-g][1]benzopyran-6''-yl)-acetylamino]-3-phenylpropionic acid
  参考文献：
  名称：

  Development of a novel furocoumarin derivative inhibiting NF-κB dependent biological functions: Design, synthesis and biological effects

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2011.07.032
• 作为产物：
  描述：

  乙酰丁二酸二甲酯 在 盐酸 、 potassium carbonate 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 3.0h， 生成 methyl 2-[7-(3,3-dimethyl-2-oxobutoxy)-4-methyl-2-oxo-2H-3-chromenyl]acetate
  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

• ——
  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.
• 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.