1-(6-amino-3,5-difluoropyridin-2-yl)-7-[3-(tert-butyl-amino)azetidin-1-yl]-6-fluoro-8-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid | 888032-61-9

• 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: 1-(6-amino-3,5-difluoropyridin-2-yl)-7-[3-(tert-butyl-amino)azetidin-1-yl]-6-fluoro-8-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
• 英文别名: 1-(6-Amino-3,5-difluoropyridin-2-yl)-7-(3-tert-butylaminoazetidin-1-yl)-6-fluoro-8-methyl-4-oxo-1,4-dihydroquinolin-3-carboxylic acid；1-(6-Amino-3,5-difluoro-2-pyridinyl)-7-[3-[(1,1-dimethylethyl)amino]-1-azetidinyl]-6-fluoro-1,4-dihydro-8-methyl-4-oxo-3-quinolinecarboxylic acid；1-(6-amino-3,5-difluoropyridin-2-yl)-7-[3-(tert-butylamino)azetidin-1-yl]-6-fluoro-8-methyl-4-oxoquinoline-3-carboxylic acid
• CAS: 888032-61-9
• 化学式: C₂₃H₂₄F₃N₅O₃
• 分子量: 475.47
• InChiKey: HUDDGSWMGNIYJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  2,3,5,6-四氟吡啶 在 盐酸 、 lithium hydroxide monohydrate 、 palladium 10% on activated carbon 、 氢气 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 N-甲基吡咯烷酮 、 甲醇 、 乙醇 、 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 124.16h， 生成 1-(6-amino-3,5-difluoropyridin-2-yl)-7-[3-(tert-butyl-amino)azetidin-1-yl]-6-fluoro-8-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
  参考文献：
  名称：

  Discovery of WQ-3810: Design, synthesis, and evaluation of 7-(3-alkylaminoazetidin-1-yl)fluoro-quinolones as orally active antibacterial agents

  摘要：

  Novel 7-(3-allcylaminoazetidin-1-yl)fluoroquinolones were designed, synthesized, and evaluated for their antibacterial activities and oral absorption rates. Against Gram-negative bacteria, 10a-e, which have various alkyl groups containing different numbers of carbon atoms (C0-C3) at the C-7 alkylaminoazetidine position, showed potent and similar antibacterial activities, whereas the activity of 10f (C4, t-Bu) was significantly lower than those of 10a-e. Conversely, the oral absorption rates of 10a-e in rats increased depending on the number of carbon atoms in the alkyl groups; 10d (C3, n-Pr) and 10e (C3, i-Pr) had high oral absorption rates (>90% at 10 mg/kg). These results demonstrated that the introduction of alkyl groups onto C-7 aminoazetidine is useful for the improvement of the oral absorption rates of these drugs while maintaining their antibacterial activities. As a conclusion, from this series of fluoroquinolones, WQ-3810 (10e), having 3-isopropylaminoazetidine as the C-7 substituent, was identified as an orally active antibacterial agent with a potent in vitro activity. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.08.015

文献信息

• NOVEL PYRIDONECARBOXYLIC ACID DERIVATIVES OR SALTS THEREOF
  申请人：WAKUNAGA PHARMACEUTICAL CO., LTD.

  公开号：EP1813610B1

  公开（公告）日：2010-09-08
• US7713997B2
  申请人：——

  公开号：US7713997B2

  公开（公告）日：2010-05-11
• Discovery of WQ-3810: Design, synthesis, and evaluation of 7-(3-alkylaminoazetidin-1-yl)fluoro-quinolones as orally active antibacterial agents
  作者：Kenji Itoh、Yasuhiro Kuramoto、Hirotaka Amano、Daichi Kazamori、Akira Yazaki

  DOI：10.1016/j.ejmech.2015.08.015

  日期：2015.10

  Novel 7-(3-allcylaminoazetidin-1-yl)fluoroquinolones were designed, synthesized, and evaluated for their antibacterial activities and oral absorption rates. Against Gram-negative bacteria, 10a-e, which have various alkyl groups containing different numbers of carbon atoms (C0-C3) at the C-7 alkylaminoazetidine position, showed potent and similar antibacterial activities, whereas the activity of 10f (C4, t-Bu) was significantly lower than those of 10a-e. Conversely, the oral absorption rates of 10a-e in rats increased depending on the number of carbon atoms in the alkyl groups; 10d (C3, n-Pr) and 10e (C3, i-Pr) had high oral absorption rates (>90% at 10 mg/kg). These results demonstrated that the introduction of alkyl groups onto C-7 aminoazetidine is useful for the improvement of the oral absorption rates of these drugs while maintaining their antibacterial activities. As a conclusion, from this series of fluoroquinolones, WQ-3810 (10e), having 3-isopropylaminoazetidine as the C-7 substituent, was identified as an orally active antibacterial agent with a potent in vitro activity. (C) 2015 Elsevier Masson SAS. All rights reserved.