ethyl 5-amino-1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylate | 172602-79-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: ethyl 5-amino-1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylate
• 英文别名: Ethyl 5-amino-1-cyclopropyl-6,7-difluoro-8-methoxy-4-oxoquinoline-3-carboxylate
• CAS: 172602-79-8
• 化学式: C₁₆H₁₆F₂N₂O₄
• 分子量: 338.311
• InChiKey: BRHHPRFIEYTMNU-UHFFFAOYSA-N

物化性质

• 沸点：
  523.5±50.0 °C(Predicted)
• 密度：
  1.465±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  81.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  ethyl 5-amino-1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以90%的产率得到5-amino-1-cyclopropyl-6,7-difluoro-8-methoxy-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid
  参考文献：
  名称：

  The Synthesis, Structure-Activity, and Structure-Side Effect Relationships of a Series of 8-Alkoxy- and 5-Amino-8-alkoxyquinolone Antibacterial Agents

  摘要：

  A series of 1-cyclopropyl-6-fluoro-8-alkoxy (8-methoxy and 8-ethoxy)-quionoline-3-carboxylic acids and 1-cyclopropyl-5-amino-6-fluoro-8-alkoxyquinoline-3-carboxylic acids has been prepared and evaluated for antibacterial activity. In addition, they were also compared to quinolones with classic substitution at C-8 (H, F, Cl) and the naphthyridine nucleus in a phototoxicity and mammalian cell cytotoxicity assay. The series of 8-methoxyquinolones had antibacterial activity against Gram-positive, Gram-negative, and anaerobic bacteria equivalent to the most active 8-substituted compounds (8-F and 8-Cl). There was also a concomitant reduction in several of the potential side effects (i.e., phototoxicity and clonogenicity) compared to the most active quinolones with classic substitution at C-8. The 8-ethoxy derivatives had an even better safety profile but were significantly less active (2-3 dilutions) in the antibacterial assay.

  DOI：

  10.1021/jm00022a013
• 作为产物：
  描述：

  ethyl 1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-5-nitro-4-oxo-3-quinolinecarboxylate 在 镍 氢气 作用下， 以 四氢呋喃 为溶剂， 21.0~28.0 ℃ 、344.73 kPa 条件下， 反应 7.0h， 以36%的产率得到ethyl 5-amino-1-cyclopropyl-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinolinecarboxylate
  参考文献：
  名称：

  The Synthesis, Structure-Activity, and Structure-Side Effect Relationships of a Series of 8-Alkoxy- and 5-Amino-8-alkoxyquinolone Antibacterial Agents

  摘要：

  A series of 1-cyclopropyl-6-fluoro-8-alkoxy (8-methoxy and 8-ethoxy)-quionoline-3-carboxylic acids and 1-cyclopropyl-5-amino-6-fluoro-8-alkoxyquinoline-3-carboxylic acids has been prepared and evaluated for antibacterial activity. In addition, they were also compared to quinolones with classic substitution at C-8 (H, F, Cl) and the naphthyridine nucleus in a phototoxicity and mammalian cell cytotoxicity assay. The series of 8-methoxyquinolones had antibacterial activity against Gram-positive, Gram-negative, and anaerobic bacteria equivalent to the most active 8-substituted compounds (8-F and 8-Cl). There was also a concomitant reduction in several of the potential side effects (i.e., phototoxicity and clonogenicity) compared to the most active quinolones with classic substitution at C-8. The 8-ethoxy derivatives had an even better safety profile but were significantly less active (2-3 dilutions) in the antibacterial assay.

  DOI：

  10.1021/jm00022a013

文献信息

• Synthesis and structure–activity relationship of 4-quinolone-3-carboxylic acid based inhibitors of glycogen synthase kinase-3β
  作者：Oana M. Cociorva、Bei Li、Tyzoon Nomanbhoy、Qiang Li、Ayako Nakamura、Kai Nakamura、Masahiro Nomura、Kyoko Okada、Shigeki Seto、Kazuhiro Yumoto、Marek Liyanage、Melissa C. Zhang、Arwin Aban、Brandon Leen、Anna Katrin Szardenings、Jonathan S. Rosenblum、John W. Kozarich、Yasushi Kohno、Kevin R. Shreder

  DOI：10.1016/j.bmcl.2011.07.073

  日期：2011.10

  The synthesis, GSK-3 beta inhibitory activity, and anti-microbial activity of bicyclic and tricyclic derivatives of the 5,7-diamino-6-fluoro-4-quinolone-3-carboxylic acid scaffold were studied. Kinase selectivity profiling indicated that members of this class were potent and highly selective GSK-3 inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.