ethyl 7-(3-amino-1-pyrrolidinyl)-6-fluoro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylate | 177751-66-5

• 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 7-(3-amino-1-pyrrolidinyl)-6-fluoro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylate
• 英文别名: Ethyl 7-(3-aminopyrrolidin-1-yl)-6-fluoro-1,4-dihydro-4-oxo-1-(thiazol-2-yl)-1,8-naphthyridine-3-carboxylate；ethyl 7-(3-aminopyrrolidin-1-yl)-6-fluoro-4-oxo-1-(1,3-thiazol-2-yl)-1,8-naphthyridine-3-carboxylate
• CAS: 177751-66-5
• 化学式: C₁₈H₁₈FN₅O₃S
• 分子量: 403.437
• InChiKey: KCTDBBUXSDQTPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  130
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  ethyl 7-(3-amino-1-pyrrolidinyl)-6-fluoro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylate 在 sodium hydroxide 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 6-Fluoro-7-[3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]-4-oxo-1-(1,3-thiazol-2-yl)-1,8-naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and structure–activity relationships of 3-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridines as novel antitumor agents

  摘要：

  In order to obtain clinically useful antitumor agent, we have designed and synthesized various 3-substituted 1,4-dihydro4-oxo-1,(2-thiazolyl)-1,8-naphthyridines, and evaluated their cytotoxic activity. The series of novel 3-substituted derivatives synthesized in this study showed good antitumor activity against murine P388 leukemia. Particularly, the 3-formyl 1,8-naphthyridine displayed an antitumor activity equal to that of the 3-carboxy 1,8-naphthyridine against murine and human tumor cell lines as well as in vivo test for mouse leukemia. These results demonstrate that the carboxy group at the C-3 position of 1,8-naphthyridine ring is not essential for antitumor activity. In addition, the trend of cytotoxic activity for the 3-substituted 1,8-naphthyridines was different from that of antibacterial activity. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.04.011
• 作为产物：
  描述：

  ethyl 2-(2,6-dichloro-3-fluoro-5-nicotinoyl)-3-(2-thiazolylamino)acrylate 在 potassium tert-butylate 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 3.0h， 生成 ethyl 7-(3-amino-1-pyrrolidinyl)-6-fluoro-1,4-dihydro-4-oxo-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 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

文献信息

• 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
  作者：Kyoji Tomita、Yasunori Tsuzuki、Koh-ichiro Shibamori、Masanori Tashima、Fumie Kajikawa、Yuji Sato、Shigeki Kashimoto、Katsumi Chiba、Katsuhiko Hino

  DOI：10.1021/jm010057b

  日期：2002.12.1

  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.
• Synthesis and structure–activity relationships of 3-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridines as novel antitumor agents
  作者：Yasunori Tsuzuki、Kyoji Tomita、Yuji Sato、Shigeki Kashimoto、Katsumi Chiba

  DOI：10.1016/j.bmcl.2004.04.011

  日期：2004.6

  In order to obtain clinically useful antitumor agent, we have designed and synthesized various 3-substituted 1,4-dihydro4-oxo-1,(2-thiazolyl)-1,8-naphthyridines, and evaluated their cytotoxic activity. The series of novel 3-substituted derivatives synthesized in this study showed good antitumor activity against murine P388 leukemia. Particularly, the 3-formyl 1,8-naphthyridine displayed an antitumor activity equal to that of the 3-carboxy 1,8-naphthyridine against murine and human tumor cell lines as well as in vivo test for mouse leukemia. These results demonstrate that the carboxy group at the C-3 position of 1,8-naphthyridine ring is not essential for antitumor activity. In addition, the trend of cytotoxic activity for the 3-substituted 1,8-naphthyridines was different from that of antibacterial activity. (C) 2004 Elsevier Ltd. All rights reserved.