2-(4-formyl-2-methoxyphenoxy)-N-(naphthalen-2-yl)acetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-(4-formyl-2-methoxyphenoxy)-N-(naphthalen-2-yl)acetamide
• 英文别名: 2-(4-formyl-2-methoxyphenoxy)-N-naphthalen-2-ylacetamide
• 化学式: C₂₀H₁₇NO₄
• 分子量: 335.359
• InChiKey: CERJKHCDUHGVTD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-formyl-2-methoxyphenoxy)-N-(naphthalen-2-yl)acetamide 、 2-氨基苯甲酰胺 在 碘 、 sodium acetate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以82.28%的产率得到2-(2-methoxy-4-(4-oxo-3,4-dihydroquinazolin-2-yl)phenoxy)-N-(naphthalen-2-yl)acetamide
  参考文献：
  名称：

  CYP enzymes, expressed within live human suspension cells, are superior to widely-used microsomal enzymes in identifying potent CYP1A1/CYP1B1 inhibitors: Identification of quinazolinones as CYP1A1/CYP1B1 inhibitors that efficiently reverse B[a]P toxicity and cisplatin resistance

  摘要：

  Microsomal cytochrome P450 (CYP) enzymes, isolated from recombinant bacterial/insect/yeast cells, are extensively used for drug metabolism studies. However, they may not always portray how a developmental drug would behave in human cells with intact intracellular transport mechanisms. This study emphasizes the usefulness of human HEK293 kidney cells, grown in 'suspension' for expression of CYPs, in finding potent CYP1A1/CYP1B1 inhibitors, as possible anticancer agents. With live cell-based assays, quinazolinones 9i/9b were found to be selective CYP1A1/CYP1B1 inhibitors with IC50 values of 30/21 nM, and > 150-fold selectivity over CYP2/3 enzymes, whereas they were far less active using commercially-available CYP1A1/CYP1B1 microsomal enzymes (IC50, > 10/1.3-1.7 mu M). Compound 9i prevented CYP1A1-mediated benzo [a]pyrene-toxicity in normal fibroblasts whereas 9b completely reversed cisplatin resistance in PC-3/prostate, COR-L23/1ung, MIAPaCa-2/pancreatic and LS174T/colon cancer cells, underlining the human-cell-assays' potential. Our results indicate that the most potent CYP1A1/CYP1B1 inhibitors would not have been identified if one had relied merely on microsomal enzymes.

  DOI：

  10.1016/j.ejps.2019.02.016
• 作为产物：
  描述：

  2-萘胺 在 potassium carbonate 、 溶剂黄146 、 potassium iodide 作用下， 以 丙酮 为溶剂， 生成 2-(4-formyl-2-methoxyphenoxy)-N-(naphthalen-2-yl)acetamide
  参考文献：
  名称：

  CYP enzymes, expressed within live human suspension cells, are superior to widely-used microsomal enzymes in identifying potent CYP1A1/CYP1B1 inhibitors: Identification of quinazolinones as CYP1A1/CYP1B1 inhibitors that efficiently reverse B[a]P toxicity and cisplatin resistance

  摘要：

  Microsomal cytochrome P450 (CYP) enzymes, isolated from recombinant bacterial/insect/yeast cells, are extensively used for drug metabolism studies. However, they may not always portray how a developmental drug would behave in human cells with intact intracellular transport mechanisms. This study emphasizes the usefulness of human HEK293 kidney cells, grown in 'suspension' for expression of CYPs, in finding potent CYP1A1/CYP1B1 inhibitors, as possible anticancer agents. With live cell-based assays, quinazolinones 9i/9b were found to be selective CYP1A1/CYP1B1 inhibitors with IC50 values of 30/21 nM, and > 150-fold selectivity over CYP2/3 enzymes, whereas they were far less active using commercially-available CYP1A1/CYP1B1 microsomal enzymes (IC50, > 10/1.3-1.7 mu M). Compound 9i prevented CYP1A1-mediated benzo [a]pyrene-toxicity in normal fibroblasts whereas 9b completely reversed cisplatin resistance in PC-3/prostate, COR-L23/1ung, MIAPaCa-2/pancreatic and LS174T/colon cancer cells, underlining the human-cell-assays' potential. Our results indicate that the most potent CYP1A1/CYP1B1 inhibitors would not have been identified if one had relied merely on microsomal enzymes.

  DOI：

  10.1016/j.ejps.2019.02.016