ethyl 1,4-dihydro-4-oxo-7-(3-pyrazolyl)-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylate | 685880-30-2

• 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 1,4-dihydro-4-oxo-7-(3-pyrazolyl)-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylate
• 英文别名: ethyl 4-oxo-7-(1H-pyrazol-5-yl)-1-(1,3-thiazol-2-yl)-1,8-naphthyridine-3-carboxylate
• CAS: 685880-30-2
• 化学式: C₁₇H₁₃N₅O₃S
• 分子量: 367.388
• InChiKey: HJEZJXULFYSNBM-UHFFFAOYSA-N

物化性质

• 沸点：
  641.2±65.0 °C(Predicted)
• 密度：
  1.492±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  129
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 1,4-dihydro-4-oxo-7-(3-pyrazolyl)-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylate 在 sodium hydroxide 、 乙醇 作用下， 反应 24.0h， 以73%的产率得到4-Oxo-7-(1H-pyrazol-3-yl)-1-thiazol-2-yl-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 fluoride 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 正己烷 、 氯仿 、 甲苯 为溶剂， 反应 14.0h， 生成 ethyl 1,4-dihydro-4-oxo-7-(3-pyrazolyl)-1-(2-thiazolyl)-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