3-acetyl-6-fluoro-4-(4-fluorophenyl)quinolin-2(1H)-one | 1257535-68-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3-acetyl-6-fluoro-4-(4-fluorophenyl)quinolin-2(1H)-one
• 英文别名: 3-acetyl-6-fluoro-4-(4-fluorophenyl)-1H-quinolin-2-one
• CAS: 1257535-68-4
• 化学式: C₁₇H₁₁F₂NO₂
• 分子量: 299.277
• InChiKey: NZPMYWSPOUXVEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-氟-苯并咪唑-2-甲醛 、 3-acetyl-6-fluoro-4-(4-fluorophenyl)quinolin-2(1H)-one 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 16.25h， 以54%的产率得到(E)-6-fluoro-3-(3-(5-fluoro-1H-benzo[d]imidazol-2-yl)acryloyl)-4-(4-fluorophenyl)quinolin-2(1H)-one
  参考文献：
  名称：

  Synthesis and SAR Studies of Dual AKT/NF-κB Inhibitors Against Melanoma

  摘要：

  The protein Kinase B alpha (AKT) and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) pathways are central regulators of cellular signaling events at the basis of tumor development and progression. Both pathways are often up‐regulated in different tumor types including melanoma. We recently reported the identification of compound 1 (BI‐69A11) as inhibitor of the AKT and the NF‐κB pathways. Here, we describe SAR studies that led to novel fluorinated derivatives with increased cellular potency, reflected in efficient inhibition of AKT and IKKs. Selected compounds demonstrated effective toxicity on melanoma, breast, and prostate cell lines. Finally, a representative derivative showed promising efficacy in an in vivo melanoma xenograft model.

  DOI：

  10.1111/cbdd.12177
• 作为产物：
  描述：

  乙酰乙酸乙酯 、 2-amino-4',5-difluorobenzophenone 在 cerium(III) chloride heptahydrate 作用下， 以 neat (no solvent) 为溶剂， 反应 0.13h， 以61%的产率得到3-acetyl-6-fluoro-4-(4-fluorophenyl)quinolin-2(1H)-one
  参考文献：
  名称：

  Synthesis and SAR Studies of Dual AKT/NF-κB Inhibitors Against Melanoma

  摘要：

  The protein Kinase B alpha (AKT) and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) pathways are central regulators of cellular signaling events at the basis of tumor development and progression. Both pathways are often up‐regulated in different tumor types including melanoma. We recently reported the identification of compound 1 (BI‐69A11) as inhibitor of the AKT and the NF‐κB pathways. Here, we describe SAR studies that led to novel fluorinated derivatives with increased cellular potency, reflected in efficient inhibition of AKT and IKKs. Selected compounds demonstrated effective toxicity on melanoma, breast, and prostate cell lines. Finally, a representative derivative showed promising efficacy in an in vivo melanoma xenograft model.

  DOI：

  10.1111/cbdd.12177