ethyl 3-[(3-chloro-2-fluorobenzyl)amino]-2-[(2,6-dichloropyridin-3-yl)carbonyl]acrylate | 1616493-23-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: ethyl 3-[(3-chloro-2-fluorobenzyl)amino]-2-[(2,6-dichloropyridin-3-yl)carbonyl]acrylate
• CAS: 1616493-23-2
• 化学式: C₁₈H₁₄Cl₃FN₂O₃
• 分子量: 431.678
• InChiKey: COPZXWDEDVKQGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  27.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  68.29
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ethyl 3-[(3-chloro-2-fluorobenzyl)amino]-2-[(2,6-dichloropyridin-3-yl)carbonyl]acrylate 在 potassium carbonate 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 34.5h， 生成 7-[4-(1,3-benzothiazol-2-yl)piperazin-1-yl]-1-(3-chloro-2-fluorobenzyl)-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid hydrochloride
  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 、 3-氯-2-氟苯甲胺 以 乙醚 、 乙醇 为溶剂， 反应 2.0h， 以95%的产率得到ethyl 3-[(3-chloro-2-fluorobenzyl)amino]-2-[(2,6-dichloropyridin-3-yl)carbonyl]acrylate
  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