7-(3-amino-1-pyrrolidinyl)-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid hydrochloride

• 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: 7-(3-amino-1-pyrrolidinyl)-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid hydrochloride
• 英文别名: 7-(3-Aminopyrrolidin-1-yl)-1,4-dihydro-4-oxo-1-(thiazol-2-yl)-1,8-naphthyridine-3-carboxylic acid hydrochloride；7-(3-aminopyrrolidin-1-yl)-4-oxo-1-(1,3-thiazol-2-yl)-1,8-naphthyridine-3-carboxylic acid;hydrochloride
• 化学式: C₁₆H₁₅N₅O₃S*ClH
• 分子量: 393.854
• InChiKey: YKXQYYCFNWUZNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  141
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  7-(3-amino-1-pyrrolidinyl)-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid hydrochloride 在 盐酸 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 (2S)-N-methyl-1-phenylpropan-2-amine hydrate 为溶剂， 生成 voreloxin中间体
  参考文献：
  名称：

  Compounds, processes for the preparation thereof and anti-tumor agents

  摘要：

  本发明涉及具有以下通式的吡啶酮羧酸衍生物或其盐：##STR1##其中R1为氢原子、卤素原子等，R2为羧基等，R3为氢原子等，A为氮原子或CH，m为1或2，Y为可消除基团或具有以下通式的基团：##STR2##其中R4为氢原子或低级烷基，Z为氢原子、低级烷基等，R5为氢原子、低级烷基等，n为0或1，p为1、2、3或4，以及制备这些化合物的方法，并且进一步涉及含有上述化合物作为有效成分的抗肿瘤药物。

  公开号：

  US05817669A1
• 作为产物：
  描述：

  3-(2,6-二氯吡啶-3-基)-3-氧代丙酸乙酯 在 盐酸 、 水 、 乙酸酐 、 溶剂黄146 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 7-(3-amino-1-pyrrolidinyl)-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acid hydrochloride
  参考文献：
  名称：

  新型萘啶酮衍生物的合成及其体外抗肿瘤活性

  摘要：

  摘要设计合成了一系列基于1a（伏立新毒素的前体）的萘啶酮衍生物。通过SRB分析进一步评估了对30μmol/ L的HL60抑制率> 70％的7种化合物的体外抗肿瘤活性。结果表明，噻唑-2-基和3-氨基甲基-4-苄氧基亚氨基-3-甲基吡咯烷-1-基分别在萘啶酮核心的N-1和C-7位置上最佳。10j表现出广谱活性（IC 50：1a抗性），并且相对于两个参照物中的8个细胞系，其效力是其1.3倍至> 100倍。

  DOI：

  10.1016/j.cclet.2016.07.024

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 2
  作者：Yasunori Tsuzuki、Kyoji Tomita、Koh-ichiro Shibamori、Yuji Sato、Shigeki Kashimoto、Katsumi Chiba

  DOI：10.1021/jm0304966

  日期：2004.4.1

  We have previously reported that a series of 7-substituted 6-fluoro-1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridine-3-carboxylic acids possess moderate cytotoxic activity. In a further attempt to find clinically useful antitumor agents, we investigated the structure-activity relationships (SARs) of a new series of compounds obtained by changing the C-6 position of the fluorine atom in addition to the C-5 and C-7 positions and evaluating their cytotoxic activity against several murine and human tumor cell lines. Our results showed that the 6-unsubstituted 1,8-naphthyridine structure had the most potent cytotoxic activity against murine P388 leukemia twice that of the 6-fluoro analogue. In addition, introduction of an amino group at the C-5 position did not have any substantial effect on the cytotoxic activity, while both the 5-chloro and 5-trifluoromethyl groups decreased the cytotoxic activity by 5- to 10-fold. Moreover, aminopyrrolidine derivatives at the C-7 position showed more potent cytotoxic activity than other amines or carbon derivatives. Among the 7-(3-aminopyrrolidinyl) derivatives, the trans-3-methoxy-4-methylaminopyrrolidinyI derivative (271) was determined to have potent cytotoxic activity in both in vitro and in vivo assays and high water solubility. Finally, the (SS)-isomer (AG-7352, 3) of 271, with a cytotoxic activity against human tumor cell lines more potent than that of etoposide, was selected for further development.
• NOVEL COMPOUND, PROCESS FOR PRODUCING THE SAME, AND ANTITUMOR AGENT
  申请人：DAINIPPON PHARMACEUTICAL CO., LTD.

  公开号：EP0787726B1

  公开（公告）日：2001-11-28
• US5817669A
  申请人：——

  公开号：US5817669A

  公开（公告）日：1998-10-06
• Compounds, processes for the preparation thereof and anti-tumor agents
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US05817669A1

  公开（公告）日：1998-10-06

  This invention relates to pyridone-carboxylic acid derivatives of the following formula or salts thereof: ##STR1## wherein R.sub.1 is a hydrogen atom, a halogen atom, etc., R.sub.2 is a carboxyl group etc., R.sub.3 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: ##STR2## wherein R.sub.4 is a hydrogen atom or a lower alkyl group, Z is a hydrogen atom, a lower alkyl group, etc., R.sub.5 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.

  本发明涉及具有以下通式的吡啶酮羧酸衍生物或其盐：##STR1##其中R1为氢原子、卤素原子等，R2为羧基等，R3为氢原子等，A为氮原子或CH，m为1或2，Y为可消除基团或具有以下通式的基团：##STR2##其中R4为氢原子或低级烷基，Z为氢原子、低级烷基等，R5为氢原子、低级烷基等，n为0或1，p为1、2、3或4，以及制备这些化合物的方法，并且进一步涉及含有上述化合物作为有效成分的抗肿瘤药物。
• Synthesis and in vitro antitumor activity of novel naphthyridinone derivatives
  作者：Xue-Dong Jia、Shuo Wang、Ming-Hua Wang、Ming-Liang Liu、Gui-Min Xia、Xiu-Jun Liu、Yun Chai、Hong-Wei He

  DOI：10.1016/j.cclet.2016.07.024

  日期：2017.2

  inhibition against HL60 at 30 μmol/L were further evaluated for their in vitro antitumor activity by SRB assay. Results reveal that thiazol-2-yl and 3-aminomethyl-4-benzyloxyimino-3-methylpyrrolidin-1-yl groups are optimal at the N-1 and C-7 positions of naphthyridinone core, respectively. 10j exhibits broad-spectrum activity (IC 50 : 1a -resistant ones, and is 1.3-fold to >100-fold more potent than the

  摘要设计合成了一系列基于1a（伏立新毒素的前体）的萘啶酮衍生物。通过SRB分析进一步评估了对30μmol/ L的HL60抑制率> 70％的7种化合物的体外抗肿瘤活性。结果表明，噻唑-2-基和3-氨基甲基-4-苄氧基亚氨基-3-甲基吡咯烷-1-基分别在萘啶酮核心的N-1和C-7位置上最佳。10j表现出广谱活性（IC 50：1a抗性），并且相对于两个参照物中的8个细胞系，其效力是其1.3倍至> 100倍。