ethyl 5,8-dihydro-2-methanesulfonyl-5-oxo-8-(2-thiazolyl)pyrido[2,3-d]pyrimidine-6-carboxylate | 174726-98-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: ethyl 5,8-dihydro-2-methanesulfonyl-5-oxo-8-(2-thiazolyl)pyrido[2,3-d]pyrimidine-6-carboxylate
• 英文别名: ethyl 2-methanesulfonyl-5-oxo-8-(1,3-thiazol-2-yl)-5H,8H-pyrido[2,3-d]pyrimidine-6-carboxylate；5,8-dihydro-2-methanesulfonyl-5-oxo-8-(2-thiazolyl)pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester；Ethyl 5,8-dihydro-2-(methylsulfonyl)-5-oxo-8-(thiazol-2-yl)pyrido[2,3-d]pyrimidine-6-carboxylate；ethyl 2-methylsulfonyl-5-oxo-8-(1,3-thiazol-2-yl)pyrido[2,3-d]pyrimidine-6-carboxylate
• CAS: 174726-98-8
• 化学式: C₁₄H₁₂N₄O₅S₂
• 分子量: 380.405
• InChiKey: AATNGLCGSQKPNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  156
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  ethyl 5,8-dihydro-2-methanesulfonyl-5-oxo-8-(2-thiazolyl)pyrido[2,3-d]pyrimidine-6-carboxylate 在 sodium hydroxide 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 0.67h， 生成 2-(3-amino-1-pyrrolidinyl)-5,8-dihydro-5-oxo-8-(2-thiazolyl)pyrido[2,3-d]pyrimidine-6-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 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：

  4-氯-2-甲巯基嘧啶-5-甲酰氯 在 甲基溴化镁 、 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 二氯甲烷 、 异丙醚 为溶剂， 反应 23.33h， 生成 ethyl 5,8-dihydro-2-methanesulfonyl-5-oxo-8-(2-thiazolyl)pyrido[2,3-d]pyrimidine-6-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。
• NOVEL COMPOUND, PROCESS FOR PRODUCING THE SAME, AND ANTITUMOR AGENT
  申请人：DAINIPPON PHARMACEUTICAL CO., LTD.

  公开号：EP0787726A1

  公开（公告）日：1997-08-06

  This invention relates to pyridone-carboxylic acid derivatives of the following formula or salts thereof:    wherein R1 is a hydrogen atom, a halogen atom, etc., R2 is a carboxyl group etc., R3 is a hydrogen atom etc., A is a nitrogen atom or CH, m is 1 or 2, and Y is an eliminable group or a group having the following formula:    wherein R4 is a hydrogen atom or a lower alkyl group, Z is a hydrogen atom, a lower alkyl group, etc., R5 is a hydrogen atom, a lower alkyl group, etc., n is 0 or 1, and p is 1, 2, 3 or 4 and to processes for the preparation of these compounds, and further to anti-tumor agents which contain the above compounds as effective ingredients.

  本发明涉及下式的吡啶酮-羧酸衍生物或其盐类： 其中 R1 是氢原子、卤素原子等 R2 是羧基等 R3 是氢原子等 A 是氮原子或 CH、 m 是 1 或 2，以及 Y 是可消除基团或具有下式的基团： 其中 R4 是氢原子或低级烷基、 Z 是氢原子、低级烷基等、 R5 是氢原子、低级烷基等、 n 是 0 或 1，以及 p 是 1、2、3 或 4 以及制备这些化合物的工艺，以及含有上述化合物作为有效成分的抗肿瘤制剂。
• 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.