1-cyclopropyl-8-methyl-4-oxo-7-(4-oxopiperidine-1-yl)-1,4-dihydro-3-quinoline carboxylic acid | 1418294-08-2

• 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-cyclopropyl-8-methyl-4-oxo-7-(4-oxopiperidine-1-yl)-1,4-dihydro-3-quinoline carboxylic acid
• 英文别名: 1-Cyclopropyl-8-methyl-4-oxo-7-(4-oxopiperidin-1-yl)quinoline-3-carboxylic acid；1-cyclopropyl-8-methyl-4-oxo-7-(4-oxopiperidin-1-yl)quinoline-3-carboxylic acid
• CAS: 1418294-08-2
• 化学式: C₁₉H₂₀N₂O₄
• 分子量: 340.379
• InChiKey: QVMPBXPRXMELHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  77.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-哌啶酮 、 6-cyclopropyl-2,2,8-trifluoro-7-methyl-2,6-dihydro-4H-1l3,2l4-[1,3,2]dioxaborinino[5,6-c]quinolin-4-one 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 24.0h， 以40%的产率得到1-cyclopropyl-8-methyl-4-oxo-7-(4-oxopiperidine-1-yl)-1,4-dihydro-3-quinoline carboxylic acid
  参考文献：
  名称：

  6-Hydrogen-8-Methylquinolones Active Against Replicating and Non-replicatingMycobacterium tuberculosis

  摘要：

  The screening of an in‐house quinolones library against Mycobacterium tuberculosis (Mtb) H37Rv, followed by a first cycle of optimization, yielded 6‐hydrogen‐8‐methyl derivatives endowed with good potency. The antitubercular activity also encompassed the bacteria in a non‐replicating state (NRP‐TB) with minimum inhibitory concentration values lower than those of the reference agent, moxifloxacin. Among the best compounds, 11w and 11ai, characterized by a properly substituted piperidine at the C‐7 position, were active against single‐drug‐resistant (SDR‐TB) Mtb strains, maintaining overall good potency also against ciprofloxacin‐resistant Mtb. This study expands the body of SAR around antitubercular quinolones leading to reconsider the role played by the usual fluorine atom at the C‐6 position. Further elaboration of the 6‐hydrogen‐8‐methylquinolone scaffold, with a particular focus on the C‐7 position, is expected to give even more potent congeners holding promise for shortening the current anti‐TB regimen.

  DOI：

  10.1111/cbdd.12022

文献信息

• 6-Hydrogen-8-Methylquinolones Active Against Replicating and Non-replicating<i>Mycobacterium tuberculosis</i>
  作者：Oriana Tabarrini、Stefano Sabatini、Serena Massari、Marco Pieroni、Scott G. Franzblau、Violetta Cecchetti

  DOI：10.1111/cbdd.12022

  日期：2012.11

  The screening of an in‐house quinolones library against Mycobacterium tuberculosis (Mtb) H37Rv, followed by a first cycle of optimization, yielded 6‐hydrogen‐8‐methyl derivatives endowed with good potency. The antitubercular activity also encompassed the bacteria in a non‐replicating state (NRP‐TB) with minimum inhibitory concentration values lower than those of the reference agent, moxifloxacin. Among the best compounds, 11w and 11ai, characterized by a properly substituted piperidine at the C‐7 position, were active against single‐drug‐resistant (SDR‐TB) Mtb strains, maintaining overall good potency also against ciprofloxacin‐resistant Mtb. This study expands the body of SAR around antitubercular quinolones leading to reconsider the role played by the usual fluorine atom at the C‐6 position. Further elaboration of the 6‐hydrogen‐8‐methylquinolone scaffold, with a particular focus on the C‐7 position, is expected to give even more potent congeners holding promise for shortening the current anti‐TB regimen.