Ethyl 6-fluoro-7-chloro-1-(1,3,4-thiadiazol-2-yl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate | 152555-76-5

• 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-chloro-1-(1,3,4-thiadiazol-2-yl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate
• 英文别名: Ethyl 7-chloro-6-fluoro-4-oxo-1-(1,3,4-thiadiazol-2-yl)-1,8-naphthyridine-3-carboxylate
• CAS: 152555-76-5
• 化学式: C₁₃H₈ClFN₄O₃S
• 分子量: 354.749
• InChiKey: HMXMEKPLGVPTJS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  114
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  Ethyl 6-fluoro-7-chloro-1-(1,3,4-thiadiazol-2-yl)-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylate 在 20percent aq. HCl 作用下， 以 乙腈 为溶剂， 生成 7-(3-Amino-pyrrolidin-1-yl)-6-fluoro-4-oxo-1-[1,3,4]thiadiazol-2-yl-1,4-dihydro-[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：

  ethyl 3-(2,6-dichloro-5-fluoropyridin-3-yl)-3-oxopropanoate 在 乙酸酐 、 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 生成 Ethyl 6-fluoro-7-chloro-1-(1,3,4-thiadiazol-2-yl)-1,4-dihydro-4-oxo-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 QUINOLONE DERIVATIVE OR SALT THEREOF AND ANTIBACTERIAL CONTAINING THE SAME
  申请人：WAKUNAGA SEIYAKU KABUSHIKI KAISHA

  公开号：EP0596126A1

  公开（公告）日：1994-05-11

  A quinolone derivative represented by general formula (1) or a salt thereof, and an antibacterial containing the same as the active ingredient, wherein R1 represents hydrogen or a protective group; R2 represents hydrogen, halogen or lower alkyl; X represents hydrogen or halogen; Y represents halogen, optionally substituted cyclic amino, optionally substituted lower cycloalkenyl, or R3-(CH2)m,-A- wherein R3 represents hydrogen or optionally substituted amino, A represents oxygen or sulfur, and m represents a number of 0 to 3; Z represents nitrogen or C-R4 wherein R4 represents hydrogen or halogen; W represents an optionally substituted five-membered heterocyclic group having three or more heteroatoms among which at least two are nitrogen; and n represents a number of 0 to 2. This compound has a potent antibacterial activity and a high safety, thus being useful as human and animal drugs, medicines for fish, agricultural chemicals, and food preservatives.

  由通式(1)代表的喹诺酮衍生物或其盐，以及含有相同作为活性成分的抗菌剂，其中R1代表氢或保护基团；R2代表氢、卤素或低级烷基；X代表氢或卤素；Y 代表卤素、任选取代的环氨基、任选取代的低级环烯基或 R3-(CH2)m,-A-，其中 R3 代表氢或任选取代的氨基，A 代表氧或硫，m 代表 0 至 3 的数字；Z 代表氮或 C-R4，其中 R4 代表氢或卤素；W 代表任选取代的五元杂环基团，该基团具有三个或三个以上杂原子，其中至少两个为氮；n 代表 0 至 2 的数字。这种化合物具有很强的抗菌活性和很高的安全性，因此可用作人类和动物药物、鱼类药物、农药和食品防腐剂。
• US5412098A
  申请人：——

  公开号：US5412098A

  公开（公告）日：1995-05-02
• 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.