Ethyl 7-ethenyl-4-oxo-1-(1,3-thiazol-2-yl)-1,8-naphthyridine-3-carboxylate | 685880-26-6

• 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 7-ethenyl-4-oxo-1-(1,3-thiazol-2-yl)-1,8-naphthyridine-3-carboxylate
• CAS: 685880-26-6
• 化学式: C₁₆H₁₃N₃O₃S
• 分子量: 327.364
• InChiKey: AYMYCXVYJJUAHS-UHFFFAOYSA-N

物化性质

• 沸点：
  518.5±60.0 °C(Predicted)
• 密度：
  1.391±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Ethyl 7-ethenyl-4-oxo-1-(1,3-thiazol-2-yl)-1,8-naphthyridine-3-carboxylate 在 盐酸 、 乙醇 作用下， 反应 10.0h， 生成 4-Oxo-1-thiazol-2-yl-7-vinyl-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Novel 7-Substituted 1,4-Dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic Acids as Antitumor Agents. Part 2

  摘要：

  We have previously reported that a series of 7-substituted 6-fluoro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids possess moderate cytotoxic activity. In a further attempt to find clinically useful antitumor agents, we investigated the structure-activity relationships (SARs) of a new series of compounds obtained by changing the C-6 position of the fluorine atom in addition to the C-5 and C-7 positions and evaluating their cytotoxic activity against several murine and human tumor cell lines. Our results showed that the 6-unsubstituted 1,8-naphthyridine structure had the most potent cytotoxic activity against murine P388 leukemia twice that of the 6-fluoro analogue. In addition, introduction of an amino group at the C-5 position did not have any substantial effect on the cytotoxic activity, while both the 5-chloro and 5-trifluoromethyl groups decreased the cytotoxic activity by 5- to 10-fold. Moreover, aminopyrrolidine derivatives at the C-7 position showed more potent cytotoxic activity than other amines or carbon derivatives. Among the 7-(3-aminopyrrolidinyl) derivatives, the trans-3-methoxy-4-methylaminopyrrolidinyI derivative (271) was determined to have potent cytotoxic activity in both in vitro and in vivo assays and high water solubility. Finally, the (SS)-isomer (AG-7352, 3) of 271, with a cytotoxic activity against human tumor cell lines more potent than that of etoposide, was selected for further development.

  DOI：

  10.1021/jm0304966
• 作为产物：
  描述：

  ethyl 2-(2,6-dichloro-3-nicotinoyl)-3-(2-thiazolylamino)acrylate 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 4.0h， 生成 Ethyl 7-ethenyl-4-oxo-1-(1,3-thiazol-2-yl)-1,8-naphthyridine-3-carboxylate
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Novel 7-Substituted 1,4-Dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic Acids as Antitumor Agents. Part 2

  摘要：

  We have previously reported that a series of 7-substituted 6-fluoro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids possess moderate cytotoxic activity. In a further attempt to find clinically useful antitumor agents, we investigated the structure-activity relationships (SARs) of a new series of compounds obtained by changing the C-6 position of the fluorine atom in addition to the C-5 and C-7 positions and evaluating their cytotoxic activity against several murine and human tumor cell lines. Our results showed that the 6-unsubstituted 1,8-naphthyridine structure had the most potent cytotoxic activity against murine P388 leukemia twice that of the 6-fluoro analogue. In addition, introduction of an amino group at the C-5 position did not have any substantial effect on the cytotoxic activity, while both the 5-chloro and 5-trifluoromethyl groups decreased the cytotoxic activity by 5- to 10-fold. Moreover, aminopyrrolidine derivatives at the C-7 position showed more potent cytotoxic activity than other amines or carbon derivatives. Among the 7-(3-aminopyrrolidinyl) derivatives, the trans-3-methoxy-4-methylaminopyrrolidinyI derivative (271) was determined to have potent cytotoxic activity in both in vitro and in vivo assays and high water solubility. Finally, the (SS)-isomer (AG-7352, 3) of 271, with a cytotoxic activity against human tumor cell lines more potent than that of etoposide, was selected for further development.

  DOI：

  10.1021/jm0304966