3-(4-甲氧基萘-1-基)-3H-2-苯并呋喃-1-酮 | 60049-53-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 中文名称: 3-(4-甲氧基萘-1-基)-3H-2-苯并呋喃-1-酮
• 英文名称: 3-(4'-methoxynaphthyl)-2-brnofuran-1(H)-one
• 英文别名: 3-(4-methoxynaphthalen-1-yl)isobenzofuran-1(3H)-one；3-(4-Methoxyl-1-naphthyl)phthalid；3-(4-methoxy-naphthalen-1-yl)-3H-isobenzofuran-1-one；3-(4-Methoxy-1-naphthyl)-2-benzofuran-1(3H)-one；3-(4-methoxynaphthalen-1-yl)-3H-2-benzofuran-1-one
• CAS: 60049-53-8
• 化学式: C₁₉H₁₄O₃
• 分子量: 290.318
• InChiKey: QCKWGWOGNUTXTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-甲氧基萘-1-基)-3H-2-苯并呋喃-1-酮 在 吡啶 、 potassium permanganate 、 potassium hydroxide 作用下， 以 水 为溶剂， 反应 5.0h， 以36%的产率得到o-(4-methoxynaphthoyl)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：

  4-溴萘酚 在 正丁基锂 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醚 、 正庚烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 6.0h， 生成 3-(4-甲氧基萘-1-基)-3H-2-苯并呋喃-1-酮
  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

文献信息

• Purohit, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2001, vol. 40, # 3, p. 222 - 227
  作者：Purohit

  DOI：——

  日期：——
• NEWMAN M. S.; VENKATESWARAN S.; SANKARAN V., J. ORG. CHEM. <JOCE-AH>, 1975, 40, NO 20, 2996-2998
  作者：NEWMAN M. S.、 VENKATESWARAN S.、 SANKARAN V.

  DOI：——

  日期：——
• 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
  作者：Carmen Cerchia、Rosarita Nasso、Matteo Mori、Stefania Villa、Arianna Gelain、Alessandra Capasso、Federica Aliotta、Martina Simonetti、Rosario Rullo、Mariorosario Masullo、Emmanuele De Vendittis、Maria Rosaria Ruocco、Antonio Lavecchia

  DOI：10.1021/acs.jmedchem.9b00632

  日期：2019.8.8

  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.