ethyl 3-(3-methoxy-1-naphthylamino)benzoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: ethyl 3-(3-methoxy-1-naphthylamino)benzoate
• 英文别名: Cdc25B-IN-1；ethyl 3-[(3-methoxynaphthalen-1-yl)amino]benzoate
• 化学式: C₂₀H₁₉NO₃
• 分子量: 321.376
• InChiKey: UCMCQFKDMRVNDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-(3-methoxy-1-naphthylamino)benzoate 在 水 、 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 0.67h， 以96%的产率得到3-(3-methoxy-1-naphthylamino)benzoic acid
  参考文献：
  名称：

  Discovery of Novel Naphthylphenylketone and Naphthylphenylamine Derivatives as Cell Division Cycle 25B (CDC25B) Phosphatase Inhibitors: Design, Synthesis, Inhibition Mechanism, and in Vitro Efficacy against Melanoma Cell Lines

  摘要：

  CDC25 phosphatases play a critical role in the regulation of the cell cycle and thus represent attractive cancer therapeutic targets. We previously discovered the 4-(2-carboxybenzoyl)phthalic acid (NSC28620) as a new CDC25 inhibitor endowed with promising anticancer activity in breast, prostate, and leukemia cells. Herein, we report a structure-based optimization of NSC28620, leading to the identification of a series of novel naphthylphenylketone and naphthylphenylamine derivatives as CDC25B inhibitors. Compounds 7j, 7i, 6e, 7f, and 3 showed higher inhibitory activity than the initial lead, with Ki values in the low micromolar range. Kinetic analysis, intrinsic fluorescence studies, and induced fit docking simulations provided a mechanistic understanding of the activity of these derivatives. All compounds were tested in the highly aggressive human melanoma cell lines A2058 and A375. Compound 4a potently inhibited cell proliferation and colony formation, causing an increase of the G2/M phase and a reduction of the G0/G1 phase of the cell cycle in both cell lines.

  DOI：

  10.1021/acs.jmedchem.9b00632
• 作为产物：
  描述：

  硝基萘 在 三乙基硅烷 、 sodium tetrahydroborate 、 溴 、 palladium diacetate 、 sodium hydride 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 溶剂黄146 、 丙酸 、 palladium dichloride 、 sodium nitrite 作用下， 以 乙醇 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 甲苯 、 mineral oil 为溶剂， 反应 21.59h， 生成 ethyl 3-(3-methoxy-1-naphthylamino)benzoate
  参考文献：
  名称：

  Discovery of Novel Naphthylphenylketone and Naphthylphenylamine Derivatives as Cell Division Cycle 25B (CDC25B) Phosphatase Inhibitors: Design, Synthesis, Inhibition Mechanism, and in Vitro Efficacy against Melanoma Cell Lines

  摘要：

  CDC25 phosphatases play a critical role in the regulation of the cell cycle and thus represent attractive cancer therapeutic targets. We previously discovered the 4-(2-carboxybenzoyl)phthalic acid (NSC28620) as a new CDC25 inhibitor endowed with promising anticancer activity in breast, prostate, and leukemia cells. Herein, we report a structure-based optimization of NSC28620, leading to the identification of a series of novel naphthylphenylketone and naphthylphenylamine derivatives as CDC25B inhibitors. Compounds 7j, 7i, 6e, 7f, and 3 showed higher inhibitory activity than the initial lead, with Ki values in the low micromolar range. Kinetic analysis, intrinsic fluorescence studies, and induced fit docking simulations provided a mechanistic understanding of the activity of these derivatives. All compounds were tested in the highly aggressive human melanoma cell lines A2058 and A375. Compound 4a potently inhibited cell proliferation and colony formation, causing an increase of the G2/M phase and a reduction of the G0/G1 phase of the cell cycle in both cell lines.

  DOI：

  10.1021/acs.jmedchem.9b00632