Ethyl 6-fluoro-7-(1-methyl-2,4,6,6a-tetrahydropyrrolo[3,4-b]pyrrol-5-yl)-4-oxo-1-(1,3-thiazol-2-yl)-1,8-naphthyridine-3-carboxylate | 475469-03-5

• 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 6-fluoro-7-(1-methyl-2,4,6,6a-tetrahydropyrrolo[3,4-b]pyrrol-5-yl)-4-oxo-1-(1,3-thiazol-2-yl)-1,8-naphthyridine-3-carboxylate
• CAS: 475469-03-5
• 化学式: C₂₁H₂₀FN₅O₃S
• 分子量: 441.486
• InChiKey: BYUGRMRHZKFJRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  107
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  Ethyl 6-fluoro-7-(1-methyl-2,4,6,6a-tetrahydropyrrolo[3,4-b]pyrrol-5-yl)-4-oxo-1-(1,3-thiazol-2-yl)-1,8-naphthyridine-3-carboxylate 在 20percent aq. HCl 作用下， 生成 6-Fluoro-7-(1-methyl-2,4,6,6a-tetrahydropyrrolo[3,4-b]pyrrol-5-yl)-4-oxo-1-(1,3-thiazol-2-yl)-1,8-naphthyridine-3-carboxylic acid;hydrochloride
  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 1

  摘要：

  In an attempt to search for clinically useful antitumor agents, we have discovered that a series of 1,1-disubstituted-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids possessed moderate cytotoxic activity.,We investigated the structure-activity relationships in this series of compounds by changing N-1 and C-7 positions and the core ring structure itself and evaluated the synthesized compounds against several murine and human tumor cell lines. These modifications led us to the following findings. (1) The 2-thiazolyl group at the N-1 position of the naphthyridine structure is the best substituent for antitumor activity. (2) Regarding core ring structure, the naphthyridine derivative is the most active followed by pyridopyrimidine analogue. (3) At the C-7 position, -aminopyrrolidine derivatives are more effective than other amines or thioether derivatives. Finally, the trans-3-amino-4-methoxypyrrolidinyl derivative (43j), and the 3-amino-3-methylpyrrolidinyl derivative (43f) as well as 3-aminopyrrolidinyl derivative (AT-3639, 1) were determined to be effective in in vitro and in vivo antitumor assays, and their activity was comparable to that of etoposide.

  DOI：

  10.1021/jm010057b
• 作为产物：
  描述：

  ethoxy N-(2-oxoethyl)-N-prop-2-ynylcarboxamide 在 盐酸 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 96.0h， 生成 Ethyl 6-fluoro-7-(1-methyl-2,4,6,6a-tetrahydropyrrolo[3,4-b]pyrrol-5-yl)-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 1

  摘要：

  In an attempt to search for clinically useful antitumor agents, we have discovered that a series of 1,1-disubstituted-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids possessed moderate cytotoxic activity.,We investigated the structure-activity relationships in this series of compounds by changing N-1 and C-7 positions and the core ring structure itself and evaluated the synthesized compounds against several murine and human tumor cell lines. These modifications led us to the following findings. (1) The 2-thiazolyl group at the N-1 position of the naphthyridine structure is the best substituent for antitumor activity. (2) Regarding core ring structure, the naphthyridine derivative is the most active followed by pyridopyrimidine analogue. (3) At the C-7 position, -aminopyrrolidine derivatives are more effective than other amines or thioether derivatives. Finally, the trans-3-amino-4-methoxypyrrolidinyl derivative (43j), and the 3-amino-3-methylpyrrolidinyl derivative (43f) as well as 3-aminopyrrolidinyl derivative (AT-3639, 1) were determined to be effective in in vitro and in vivo antitumor assays, and their activity was comparable to that of etoposide.

  DOI：

  10.1021/jm010057b