7-(benzo[d][1,3]dioxol-5-yl)-2-nitronaphtho[2,1-b]furan | 1192648-50-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并呋喃类
• 英文名称: 7-(benzo[d][1,3]dioxol-5-yl)-2-nitronaphtho[2,1-b]furan
• CAS: 1192648-50-2
• 化学式: C₁₉H₁₁NO₅
• 分子量: 333.3
• InChiKey: NIMJKLMCSVRHIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.89
• 重原子数：
  25.0
• 可旋转键数：
  2.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  74.74
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  3.4-(亚甲基二氧基)苯硼酸 、 7-溴-2-硝基苯并[e][1]苯并呋喃 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 反应 2.0h， 以88%的产率得到7-(benzo[d][1,3]dioxol-5-yl)-2-nitronaphtho[2,1-b]furan
  参考文献：
  名称：

  Identification of small molecule regulators of the nuclear receptor HNF4α based on naphthofuran scaffolds

  摘要：

  Nuclear receptors are ligand-activated transcription factors involved in all major physiological functions of complex organisms. In this respect, they are often described as drugable targets for a number of pathological states including hypercholesterolemia and atherosclerosis. HNF4 alpha (NR2A1) is a recently 'deorphanized' nuclear receptor which is bound in vivo by linoleic acid, although this natural ligand does not seem to promote transcriptional activation. In mouse, HNF4 alpha is a major regulator of liver development and hepatic lipid metabolism and mutations in human have been linked to diabetes. Here, we have used a yeast one-hybrid system to identify small molecule activators of HNF4 alpha in a library of synthetic compounds and found one hit bearing a methoxy group branched on a nitronaphthofuran backbone. A collection of molecules deriving from the discovered hit was generated and tested for activity toward HNF4 alpha in yeast one-hybrid system. It was found that both the nitro group and a complete naphthofuran backbone were required for full activity of the compounds. Furthermore, adding a hydroxy group at position 7 of the minimal backbone led to the most active compound of the collection. Accordingly, a direct interaction of the hydroxylated compound with the ligand binding domain of HNF4 alpha was detected by NMR and thermal denaturation assays. When used in mammalian cell culture systems, these compounds proved to be highly toxic, except when methylated on the furan ring. One such compound was able to modulate HNF4 alpha-driven transcription in transfected HepG2C3A cells. These data indicate that HNF4 alpha activity can be modulated by small molecules and suggest new routes for targeting the receptor in humans. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.07.079