Naphtho-furan-2-carboxamid | 69789-96-4

• 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: Naphtho-furan-2-carboxamid
• 英文别名: naphtho[2,1-b]furan-2-carboxylic acid amide；Naphtho[2,1-b]furan-2-carboxamide；benzo[e][1]benzofuran-2-carboxamide
• CAS: 69789-96-4
• 化学式: C₁₃H₉NO₂
• mdl: MFCD07360911
• 分子量: 211.22
• InChiKey: VQMXMQWQEILHQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  56.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  Benzo[e][1]benzofuran-2-carbonyl chloride 在 氨 作用下， 以 四氢呋喃 为溶剂， 反应 1.67h， 以125 mg的产率得到Naphtho-furan-2-carboxamid
  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

文献信息

• Enolamides, pharmaceutical compositions and methods for treating
  申请人：Warner-Lambert Company

  公开号：US04761424A1

  公开（公告）日：1988-08-02

  The present invention relates to novel enolamide type compounds, pharmaceutical compositions, and methods of use thereof, useful in the treatment of diseases in which products of lipoxygenase enzyme activity or the action of leukotrienes contribute to the pathological condition.

  本发明涉及新型烯酰胺类化合物、药物组合物及其使用方法，适用于治疗疾病，其中脂氧酶酶活性产物或白三烯的作用促成了病理状况。
• Novel enolamides, process for their manufacture and pharmaceutical compositions thereof with an activity as modulators of the arachidonic acid cascade
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0221345A1

  公开（公告）日：1987-05-13

  The present invention relates to novel enolamide type compounds, pharmaceutical compositions, and methods of use thereof, useful in the treatment of diseases in which products of lipoxygenase enzyme activity or the action of leukotrienes contribute to the pathological condition.

  本发明涉及新型烯酰胺类化合物、药物组合物及其使用方法，可用于治疗脂氧合酶酶活性产物或白三烯作用导致病理状态的疾病。
• US4761424A
  申请人：——

  公开号：US4761424A

  公开（公告）日：1988-08-02
• US4868195A
  申请人：——

  公开号：US4868195A

  公开（公告）日：1989-09-19
• US4868199A
  申请人：——

  公开号：US4868199A

  公开（公告）日：1989-09-19