ethyl 2,6-dimethoxy-5-nitronicotinoylacetate | 685879-39-4

• 分子结构分类: 有机化合物 - 有机1,3-偶极化合物 - 烯丙基型1,3-偶极有机化合物
• 英文名称: ethyl 2,6-dimethoxy-5-nitronicotinoylacetate
• 英文别名: ethyl 3-(2,6-dimethoxy-5-nitropyridin-3-yl)-3-oxopropanoate
• CAS: 685879-39-4
• 化学式: C₁₂H₁₄N₂O₇
• 分子量: 298.252
• InChiKey: VUPGVGOVVCYNBO-UHFFFAOYSA-N

物化性质

• 沸点：
  414.6±40.0 °C(Predicted)
• 密度：
  1.313±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  121
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  原甲酸三乙酯 、 ethyl 2,6-dimethoxy-5-nitronicotinoylacetate 在 乙酸酐 作用下， 反应 1.0h， 生成 ethyl 2-[(2,6-dimethoxy-5-nitropyridin-3-yl)carbonyl]-3-ethoxyacrylate
  参考文献：
  名称：

  新型1-（环丙基/叔丁基/ 4-氟苯基）-1,4-二氢-6-硝基-4-氧代-7-（取代的仲氨基）-1,8-萘啶-3-羧酸的抗分枝杆菌活性。

  摘要：

  51个1-（环丙基/叔丁基/ 4-氟苯基）-1,4-二氢-6-硝基-4-氧代-7-（取代仲氨基）-1,8-萘啶-3-羧酸合成并评估了对结核分枝杆菌H37Rv（MTB），耐多药结核分枝杆菌（MDR-TB）和耻垢分枝杆菌（MC2）的体外和体内抗分枝杆菌的作用，还测试了其抑制DNA超螺旋活性的能力耻垢分枝杆菌的促旋酶。在合成的化合物中，1-叔丁基-1,4-二氢-7-（4,4-二甲基恶唑烷-3-基）-6-硝基-4-氧代-1,8-萘吡啶-3-羧酸（10q）被发现是体外活性最高的化合物，对MTB和MDR-TB的MIC为0.1 microM，分别比异烟肼对MTB和MDR-TB的效力分别高3倍和455倍。

  DOI：

  10.1021/jm700999n
• 作为产物：
  描述：

  2,6-二甲氧基吡啶-3-羧酸 在 硝酸 、 乙酸酐 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 9.0h， 生成 ethyl 2,6-dimethoxy-5-nitronicotinoylacetate
  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 2

  摘要：

  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.

  DOI：

  10.1021/jm0304966

文献信息

• Antimycobacterial Activities of Novel 1-(Cyclopropyl/<i>tert</i>-butyl/4-fluorophenyl)-1,4-dihydro- 6-nitro-4-oxo-7-(substituted secondary amino)-1,8-naphthyridine-3-carboxylic Acid
  作者：Dharmarajan Sriram、Palaniappan Senthilkumar、Murugesan Dinakaran、Perumal Yogeeswari、Arnab China、Valakunja Nagaraja

  DOI：10.1021/jm700999n

  日期：2007.11.1

  4-dihydro-6-nitro-4-oxo-7-(substitute d secondary amino)-1,8-naphthyridine-3-carboxylic acids were synthesized and evaluated for antimycobacterial in vitro and in vivo against Mycobacterium tuberculosis H37Rv (MTB), multi-drug-resistant Mycobacterium tuberculosis (MDR-TB) and Mycobacterium smegmatis (MC2) and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis

  51个1-（环丙基/叔丁基/ 4-氟苯基）-1,4-二氢-6-硝基-4-氧代-7-（取代仲氨基）-1,8-萘啶-3-羧酸合成并评估了对结核分枝杆菌H37Rv（MTB），耐多药结核分枝杆菌（MDR-TB）和耻垢分枝杆菌（MC2）的体外和体内抗分枝杆菌的作用，还测试了其抑制DNA超螺旋活性的能力耻垢分枝杆菌的促旋酶。在合成的化合物中，1-叔丁基-1,4-二氢-7-（4,4-二甲基恶唑烷-3-基）-6-硝基-4-氧代-1,8-萘吡啶-3-羧酸（10q）被发现是体外活性最高的化合物，对MTB和MDR-TB的MIC为0.1 microM，分别比异烟肼对MTB和MDR-TB的效力分别高3倍和455倍。
• 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.