5-[[7-(Hydroxyamino)-7-oxoheptyl]amino]benzo[c][2,6]naphthyridine-8-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 5-[[7-(Hydroxyamino)-7-oxoheptyl]amino]benzo[c][2,6]naphthyridine-8-carboxylic acid
• 英文别名: 5-[[7-(hydroxyamino)-7-oxoheptyl]amino]benzo[c][2,6]naphthyridine-8-carboxylic acid
• 化学式: C₂₀H₂₂N₄O₄
• 分子量: 382.419
• InChiKey: YGFSEWGMMQRLQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.35
• 重原子数：
  28.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  124.44
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  5-[[7-(Hydroxyamino)-7-oxoheptyl]amino]benzo[c][2,6]naphthyridine-8-carboxylic acid 、 三氟乙酸 在 ACE 5 C₁₈ 作用下， 以 水 、 乙腈 为溶剂， 以40 mg的产率得到8-carboxy-5-((7-(hydroxyamino)-7-oxoheptyl)amino)benzo[c][2,6]naphthyridin-2-ium 2,2,2-trifluoroacetate
  参考文献：
  名称：

  New Dual CK2/HDAC1 Inhibitors with Nanomolar Inhibitory Activity against Both Enzymes

  摘要：

  Four potent CK2 inhibitors derived from CX-4945 are described. They also provided nanomolar activity against HDAC1, therefore having promising utility as dual-target agents for cancer. The linker length between the hydroxamic acid and the CX-4945 scaffold plays an important role in dictating balanced activity against the targeted enzymes. The seven-carbon linker (compound 15c) was optimal for inhibition of both CK2 and HDAC1. Remarkably, 15c showed 3.0 and 3.5 times higher inhibitory activity than the reference compounds CX-4945 (against CK2) and SAHA (against HDAC1), respectively. Compound 15c exhibited micromolar activity in cell-based cytotoxic assays against multiple cell lines.

  DOI：

  10.1021/acsmedchemlett.9b00561
• 作为产物：
  描述：

  7-溴庚酸 在 sodium azide 、 lithium hydroxide monohydrate 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 135.0 ℃ 、400.01 kPa 条件下， 反应 170.92h， 生成 5-[[7-(Hydroxyamino)-7-oxoheptyl]amino]benzo[c][2,6]naphthyridine-8-carboxylic acid
  参考文献：
  名称：

  New Dual CK2/HDAC1 Inhibitors with Nanomolar Inhibitory Activity against Both Enzymes

  摘要：

  Four potent CK2 inhibitors derived from CX-4945 are described. They also provided nanomolar activity against HDAC1, therefore having promising utility as dual-target agents for cancer. The linker length between the hydroxamic acid and the CX-4945 scaffold plays an important role in dictating balanced activity against the targeted enzymes. The seven-carbon linker (compound 15c) was optimal for inhibition of both CK2 and HDAC1. Remarkably, 15c showed 3.0 and 3.5 times higher inhibitory activity than the reference compounds CX-4945 (against CK2) and SAHA (against HDAC1), respectively. Compound 15c exhibited micromolar activity in cell-based cytotoxic assays against multiple cell lines.

  DOI：

  10.1021/acsmedchemlett.9b00561

文献信息

• New Dual CK2/HDAC1 Inhibitors with Nanomolar Inhibitory Activity against Both Enzymes
  作者：Loganathan Rangasamy、Irene Ortín、José María Zapico、Claire Coderch、Ana Ramos、Beatriz de Pascual-Teresa

  DOI：10.1021/acsmedchemlett.9b00561

  日期：2020.5.14

  Four potent CK2 inhibitors derived from CX-4945 are described. They also provided nanomolar activity against HDAC1, therefore having promising utility as dual-target agents for cancer. The linker length between the hydroxamic acid and the CX-4945 scaffold plays an important role in dictating balanced activity against the targeted enzymes. The seven-carbon linker (compound 15c) was optimal for inhibition of both CK2 and HDAC1. Remarkably, 15c showed 3.0 and 3.5 times higher inhibitory activity than the reference compounds CX-4945 (against CK2) and SAHA (against HDAC1), respectively. Compound 15c exhibited micromolar activity in cell-based cytotoxic assays against multiple cell lines.