ethyl 1-(3-chloro-2-fluorobenzyl)-4-oxo-7-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}-1,4-dihydro-1,8-naphthyridine-3-carboxylate | 1616492-99-9

• 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: ethyl 1-(3-chloro-2-fluorobenzyl)-4-oxo-7-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}-1,4-dihydro-1,8-naphthyridine-3-carboxylate
• CAS: 1616492-99-9
• 化学式: C₂₉H₂₅ClF₄N₄O₃
• 分子量: 588.989
• InChiKey: GFNQBCSHZJQDCC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.76
• 重原子数：
  41.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  67.67
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  ethyl 1-(3-chloro-2-fluorobenzyl)-4-oxo-7-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}-1,4-dihydro-1,8-naphthyridine-3-carboxylate 在 sodium hydroxide 、 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 0.5h， 以55%的产率得到1-(3-chloro-2-fluorobenzyl)-4-oxo-7-{4-[3-(trifluoromethyl)-phenyl]piperazin-1-yl}-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  Ethyl 1,8-Naphthyridone-3-carboxylates Downregulate Human Papillomavirus-16 E6 and E7 Oncogene Expression

  摘要：

  Strong epidemiological and molecular data associate cervical cancer (CC) with high-risk human papillomavirus (HPV) infections. The carcinogenic mechanism depends mainly on the expression of E6 and E7 oncoproteins encoded by the viral genome. Using a cell-based high-throughput assay, an in-house library of compounds was screened identifying the 1,8-naphthyridone 1 that efficiently inhibited the transcription driven by the long control region of the HPV genome. A series of analogues were then synthesized, obtaining more potent derivatives able to downregulate E6 and E7 transcripts in HPV-16-positive CC CaSki cells. An unusual structural insight emerged for the C-3 position of the 1,8-naphthyridone core, where the ethyl carboxylate esters, but not the carboxylic acids, are responsible for the activity. In vitro uptake studies showed that the 3-ethyl carboxylates do not act as prodrugs. The 1,8-naphthyridones emerged as valid starting points for the development of innovative agents potentially useful for the treatment of HPV-induced CC.

  DOI：

  10.1021/jm500340h
• 作为产物：
  描述：

  ethyl 2-[(2,6-dichloropyridin-3-yl)carbonyl]-3-(dimethylamino)acrylate 在 potassium carbonate 作用下， 以 乙醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 ethyl 1-(3-chloro-2-fluorobenzyl)-4-oxo-7-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}-1,4-dihydro-1,8-naphthyridine-3-carboxylate
  参考文献：
  名称：

  Ethyl 1,8-Naphthyridone-3-carboxylates Downregulate Human Papillomavirus-16 E6 and E7 Oncogene Expression

  摘要：

  Strong epidemiological and molecular data associate cervical cancer (CC) with high-risk human papillomavirus (HPV) infections. The carcinogenic mechanism depends mainly on the expression of E6 and E7 oncoproteins encoded by the viral genome. Using a cell-based high-throughput assay, an in-house library of compounds was screened identifying the 1,8-naphthyridone 1 that efficiently inhibited the transcription driven by the long control region of the HPV genome. A series of analogues were then synthesized, obtaining more potent derivatives able to downregulate E6 and E7 transcripts in HPV-16-positive CC CaSki cells. An unusual structural insight emerged for the C-3 position of the 1,8-naphthyridone core, where the ethyl carboxylate esters, but not the carboxylic acids, are responsible for the activity. In vitro uptake studies showed that the 3-ethyl carboxylates do not act as prodrugs. The 1,8-naphthyridones emerged as valid starting points for the development of innovative agents potentially useful for the treatment of HPV-induced CC.

  DOI：

  10.1021/jm500340h