ethyl 7-chloro-6-fluoro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylate | 108118-77-0

• 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-chloro-6-fluoro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylate
• 英文别名: ethyl 7-chloro-6-fluoro-4-oxo-1-(1,3-thiazol-2-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxylate；Ethyl 7-chloro-6-fluoro-4-oxo-1-(1,3-thiazol-2-yl)-1,8-naphthyridine-3-carboxylate
• CAS: 108118-77-0
• 化学式: C₁₄H₉ClFN₃O₃S
• 分子量: 353.761
• InChiKey: YABVRQLZBJZYFK-UHFFFAOYSA-N

物化性质

• 沸点：
  529.3±60.0 °C(Predicted)
• 密度：
  1.568±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 7-chloro-6-fluoro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylate 在 三乙胺 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 4.0h， 生成 Ethyl 7-(2-acetamidoethylsulfanyl)-6-fluoro-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
• 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 为溶剂， 反应 2.0h， 以63%的产率得到ethyl 7-chloro-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

• NOVEL PYRIDONE CARBOXYLIC ACID DERIVATIVE OR SALT THEREOF
  申请人：WAKUNAGA PHARMACEUTICAL CO., LTD.

  公开号：US20200062752A1

  公开（公告）日：2020-02-27

  It is intended to provide a novel compound having high antitumor activity and low toxicity to normal cells. The present invention provides a pyridone carboxylic acid derivative represented by the following formula (1) or a salt thereof wherein R 1 represents a hydrogen atom, a halogen atom or the like; R 2 represents a hydrogen atom, a halogen atom or the like; R 3 to R 6 each represent a hydrogen atom or the like; R 7 represents a hydrogen atom or the like; R 8 represents a hydrogen atom, a halogen atom, the following formula (a) (wherein R a1 and R a2 each represent a hydrogen atom, a hydroxy group, an optionally substituted lower alkyl group or the like) or the like, or R 7 and R 8 together represent —N—OR 10 (wherein R 10 represents a hydrogen atom, an optionally substituted lower alkyl group, or an aralkyl group), or R 7 and R 8 form an optionally substituted 4- to 6-membered saturated hetero ring together with the adjacent carbon atom, or the like; R 9 represents a hydrogen atom or the like; X represents a nitrogen atom or the like; and Y represents a nitrogen atom or the like.

  本发明旨在提供一种具有高抗肿瘤活性和低毒性对正常细胞的新型化合物。本发明提供一种由以下式(1)表示的吡啶酮羧酸衍生物或其盐，其中R1代表氢原子、卤素原子或类似物；R2代表氢原子、卤素原子或类似物；R3至R6各自代表氢原子或类似物；R7代表氢原子或类似物；R8代表氢原子、卤素原子、以下式(a)（其中Ra1和Ra2各自代表氢原子、羟基、可选择取代的低烷基基团或类似物）或类似物，或者R7和R8一起代表—N—OR10（其中R10代表氢原子、可选择取代的低烷基基团或芳基烷基基团），或者R7和R8与相邻碳原子一起形成可选择取代的4-至6元饱和杂环，或类似物；R9代表氢原子或类似物；X代表氮原子或类似物；Y代表氮原子或类似物。
• Heterocyclic substituted 1,4-dihydri-4-0x9-1,8-naphthyridine analogs
  申请人：Whitten P. Jeffrey

  公开号：US20050004160A1

  公开（公告）日：2005-01-06

  The present invention relates to 1,4-dihydro-4-oxo-1,8-napthpyridine analogs of the formula and pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein A, X, W and Y are substituents. The present invention relates to methods for using such compounds.

  本发明涉及式 1,4-二氢-4-氧代-1,8-萘吡啶类似物及其药物可接受的盐类、酯类和原药，其中 A、X、W 和 Y 为取代基。 及其药学上可接受的盐、酯和原药，其中A、X、W和Y为取代基。本发明涉及使用此类化合物的方法。
• Heterocyclic substituted 1,4-dihydro-4-oxo-1,8-naphthpyridine analogs
  申请人：Whitten P. Jeffrey

  公开号：US20070010512A1

  公开（公告）日：2007-01-11

  The present invention relates to 1,4-dihydro-4-oxo-1,8-napthpyridine analogs of the formula and pharmaceutically acceptable salts, esters, and prodrugs thereof, wherein A, X, W and Y are substituents. The present invention also relates to methods for using such compounds.
• US7163948B2
  申请人：——

  公开号：US7163948B2

  公开（公告）日：2007-01-16