ethyl 1-(3-tert-butoxycarbonylamino-4-fluorophenyl)-7-chloro-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate | 535170-22-0

• 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 1-(3-tert-butoxycarbonylamino-4-fluorophenyl)-7-chloro-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate
• 英文别名: Ethyl 7-chloro-6-fluoro-1-[4-fluoro-3-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]-4-oxo-1,8-naphthyridine-3-carboxylate
• CAS: 535170-22-0
• 化学式: C₂₂H₂₀ClF₂N₃O₅
• 分子量: 479.868
• InChiKey: QFMKNKRLVWEXAX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  97.8
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl 1-(3-tert-butoxycarbonylamino-4-fluorophenyl)-7-chloro-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate 在 盐酸 、 溶剂黄146 作用下， 以94%的产率得到1-(3-amino-4-fluorophenyl)-7-chloro-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  A Novel Antibacterial 8-Chloroquinolone with a Distorted Orientation of the N1-(5-Amino-2,4-difluorophenyl) Group

  摘要：

  Fluoroquinolones represent a major class of antibacterial agents with great therapeutic potential. In this study, we designed m-aminophenyl groups as novel N-1 substituents of naphthyridones and quinolones. Among newly synthesized compounds, 7-(3-aminoazetidin-1-yl)-1-(5-amino-2,4-difluorophenyl)-8-chloro-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (4) has extremely potent antibacterial activities against Gram (+) as well as Gram (-) bacteria. This compound is significantly more potent than trovafloxacin against clinical isolates: 30 times against Streptococcus pneumoniae and 128 times against methicillin resistant Staphylococcus aureus. The structure-activity relationship (SAR) study revealed that a limited combination of 1-(5-amino-2,4-difluorophenyl) group, 7-(azetidin-1-yl) group, and 8-Cl atom (or Br atom or Me group) gave potent antibacterial activity. An X-ray crystallographic study of a 7-(3-ethylaminoazetidin-1-yl)-8-chloro derivative demonstrated that the N-1 aromatic group was remarkably distorted out of the core quinolone plane by steric repulsion between the C-8 C1 atom and the N-1 substituent. Furthermore, a molecular modeling study of 4 and its analogues demonstrated that a highly distorted orientation was induced by a steric hindrance of the C-8 substituent, such as Cl, Br, or a methyl group. Thus, their highly strained conformation should be a key factor for the potent antibacterial activity.

  DOI：

  10.1021/jm0205090
• 作为产物：
  描述：

  (3-氨基-4-氟苯基)-氨基甲酸叔丁酯 在 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl 1-(3-tert-butoxycarbonylamino-4-fluorophenyl)-7-chloro-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylate
  参考文献：
  名称：

  A Novel Antibacterial 8-Chloroquinolone with a Distorted Orientation of the N1-(5-Amino-2,4-difluorophenyl) Group

  摘要：

  Fluoroquinolones represent a major class of antibacterial agents with great therapeutic potential. In this study, we designed m-aminophenyl groups as novel N-1 substituents of naphthyridones and quinolones. Among newly synthesized compounds, 7-(3-aminoazetidin-1-yl)-1-(5-amino-2,4-difluorophenyl)-8-chloro-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (4) has extremely potent antibacterial activities against Gram (+) as well as Gram (-) bacteria. This compound is significantly more potent than trovafloxacin against clinical isolates: 30 times against Streptococcus pneumoniae and 128 times against methicillin resistant Staphylococcus aureus. The structure-activity relationship (SAR) study revealed that a limited combination of 1-(5-amino-2,4-difluorophenyl) group, 7-(azetidin-1-yl) group, and 8-Cl atom (or Br atom or Me group) gave potent antibacterial activity. An X-ray crystallographic study of a 7-(3-ethylaminoazetidin-1-yl)-8-chloro derivative demonstrated that the N-1 aromatic group was remarkably distorted out of the core quinolone plane by steric repulsion between the C-8 C1 atom and the N-1 substituent. Furthermore, a molecular modeling study of 4 and its analogues demonstrated that a highly distorted orientation was induced by a steric hindrance of the C-8 substituent, such as Cl, Br, or a methyl group. Thus, their highly strained conformation should be a key factor for the potent antibacterial activity.

  DOI：

  10.1021/jm0205090

文献信息

• A Novel Antibacterial 8-Chloroquinolone with a Distorted Orientation of the N1-(5-Amino-2,4-difluorophenyl) Group
  作者：Yasuhiro Kuramoto、Yoshihiro Ohshita、Jiro Yoshida、Akira Yazaki、Motoo Shiro、Tohru Koike

  DOI：10.1021/jm0205090

  日期：2003.5.1

  Fluoroquinolones represent a major class of antibacterial agents with great therapeutic potential. In this study, we designed m-aminophenyl groups as novel N-1 substituents of naphthyridones and quinolones. Among newly synthesized compounds, 7-(3-aminoazetidin-1-yl)-1-(5-amino-2,4-difluorophenyl)-8-chloro-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (4) has extremely potent antibacterial activities against Gram (+) as well as Gram (-) bacteria. This compound is significantly more potent than trovafloxacin against clinical isolates: 30 times against Streptococcus pneumoniae and 128 times against methicillin resistant Staphylococcus aureus. The structure-activity relationship (SAR) study revealed that a limited combination of 1-(5-amino-2,4-difluorophenyl) group, 7-(azetidin-1-yl) group, and 8-Cl atom (or Br atom or Me group) gave potent antibacterial activity. An X-ray crystallographic study of a 7-(3-ethylaminoazetidin-1-yl)-8-chloro derivative demonstrated that the N-1 aromatic group was remarkably distorted out of the core quinolone plane by steric repulsion between the C-8 C1 atom and the N-1 substituent. Furthermore, a molecular modeling study of 4 and its analogues demonstrated that a highly distorted orientation was induced by a steric hindrance of the C-8 substituent, such as Cl, Br, or a methyl group. Thus, their highly strained conformation should be a key factor for the potent antibacterial activity.