N-((1H-benzo[d]imidazol-2-yl)methyl)-6-chloro-2-oxo-4-phenyl-1,2-dihydroquinoline-3-carboxamide

• 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: N-((1H-benzo[d]imidazol-2-yl)methyl)-6-chloro-2-oxo-4-phenyl-1,2-dihydroquinoline-3-carboxamide
• 英文别名: N-(1H-benzimidazol-2-ylmethyl)-6-chloro-2-oxo-4-phenyl-1H-quinoline-3-carboxamide
• 化学式: C₂₄H₁₇ClN₄O₂
• 分子量: 428.878
• InChiKey: AAZAIGWOFRALDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  86.9
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  ethyl 6-chloro-2-oxo-4-phenyl-1,2-dihydroquinoline-3-carboxylate 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.0h， 生成 N-((1H-benzo[d]imidazol-2-yl)methyl)-6-chloro-2-oxo-4-phenyl-1,2-dihydroquinoline-3-carboxamide
  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

文献信息

• Synthesis and SAR Studies of Dual AKT/NF-κB Inhibitors Against Melanoma
  作者：Elisa Barile、Surya K. De、Yongmei Feng、Vida Chen、Li Yang、Ze'ev Ronai、Maurizio Pellecchia

  DOI：10.1111/cbdd.12177

  日期：2013.11

  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.