3-methyl-2-(4-(piperidin-1-yl)phenyl)quinolin-4(1H)-one

• 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: 3-methyl-2-(4-(piperidin-1-yl)phenyl)quinolin-4(1H)-one
• 英文别名: 3-methyl-2-[4-(1-piperidyl)phenyl]-1H-quinolin-4-one；3-methyl-2-(4-piperidin-1-ylphenyl)-1H-quinolin-4-one
• 化学式: C₂₁H₂₂N₂O
• 分子量: 318.418
• InChiKey: AWHUUXSYWGKYHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4'-氟苯丙酮 在 三氟甲磺酸 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 24.0h， 生成 3-methyl-2-(4-(piperidin-1-yl)phenyl)quinolin-4(1H)-one
  参考文献：
  名称：

  Rational Design, Synthesis, and Biological Evaluation of Heterocyclic Quinolones Targeting the Respiratory Chain of Mycobacterium tuberculosis

  摘要：

  A high-throughput screen (HTS) was undertaken against the respiratory chain dehydrogenase component, NADH:menaquinone oxidoreductase (Ndh) of Mycobacterium tuberculosis (Mtb). The 11000 compounds were selected for the HTS based on the known phenothiazine Ndh inhibitors, trifluoperazine and thioridazine. Combined HTS (11000 compounds) and in-house screening of a limited number of quinolones (50 compounds) identified similar to 100 hits and four distinct chemotypes, the most promising of which contained the quinolone core. Subsequent Mtb screening of the complete in-house quinolone library (350 compounds) identified a further similar to 90 hits across three quinolone subtemplates. Quinolones containing the amine-based side chain were selected as the pharmacophore for further modification, resulting in metabolically stable quinolones effective against multi drug resistant (MDR) Mtb. The lead compound, 42a (MTC420), displays acceptable antituberculosis activity (Mtb IC50 = 525 nM, Mtb Wayne IC50 = 76 nM, and MDR Mtb patient isolates IC50 = 140 nM) and favorable pharmacokinetic and toxicological profiles.

  DOI：

  10.1021/acs.jmedchem.6b01718

文献信息

• Combination of respiratory electron transport chain inhibitors with a cytochrome bd inhibitor
  申请人：Liverpool School of Tropical Medicine

  公开号：US10799494B2

  公开（公告）日：2020-10-13

  The present invention relates to a combination therapeutic product comprising one or more respiratory electron transport chain inhibitors and a cytochrome bd inhibitor, as defined herein, or a pharmaceutically acceptable salt thereof. The present invention also relates to pharmaceutical compositions comprising the combination therapeutic product and to the use of the combination therapeutic product in the treatment of mycobacterial infections, such as tuberculosis.

  本发明涉及一种包含一种或多种呼吸电子传递链抑制剂和细胞色素bd抑制剂（如本文所定义）或其药学上可接受的盐的组合治疗产品。本发明还涉及包含该组合治疗产品的药物组合物，以及该组合治疗产品在治疗结核病等分枝杆菌感染中的用途。
• COMBINATION PRODUCT
  申请人：Liverpool School of Tropical Medicine

  公开号：EP3389659A1

  公开（公告）日：2018-10-24
• [EN] COMBINATION PRODUCT<br/>[FR] PRODUIT COMBINÉ
  申请人：LIVERPOOL SCHOOL TROPICAL MEDICINE

  公开号：WO2017103615A1

  公开（公告）日：2017-06-22

  The present invention relates to a combination therapeutic product comprising one or more respiratory electron transport chain inhibitors and a cytochrome bd inhibitor, as defined herein, or a pharmaceutically acceptable salt thereof. The present invention also relates to pharmaceutical compositions comprising the combination therapeutic product and to the use of the combination therapeutic product in the treatment of mycobacterial infections, such as tuberculosis.
• Rational Design, Synthesis, and Biological Evaluation of Heterocyclic Quinolones Targeting the Respiratory Chain of <i>Mycobacterium tuberculosis</i>
  作者：W. David Hong、Peter D. Gibbons、Suet C. Leung、Richard Amewu、Paul A. Stocks、Andrew Stachulski、Pedro Horta、Maria L. S. Cristiano、Alison E. Shone、Darren Moss、Alison Ardrey、Raman Sharma、Ashley J. Warman、Paul T. P. Bedingfield、Nicholas E. Fisher、Ghaith Aljayyoussi、Sally Mead、Maxine Caws、Neil G. Berry、Stephen A. Ward、Giancarlo A. Biagini、Paul M. O’Neill、Gemma L. Nixon

  DOI：10.1021/acs.jmedchem.6b01718

  日期：2017.5.11

  A high-throughput screen (HTS) was undertaken against the respiratory chain dehydrogenase component, NADH:menaquinone oxidoreductase (Ndh) of Mycobacterium tuberculosis (Mtb). The 11000 compounds were selected for the HTS based on the known phenothiazine Ndh inhibitors, trifluoperazine and thioridazine. Combined HTS (11000 compounds) and in-house screening of a limited number of quinolones (50 compounds) identified similar to 100 hits and four distinct chemotypes, the most promising of which contained the quinolone core. Subsequent Mtb screening of the complete in-house quinolone library (350 compounds) identified a further similar to 90 hits across three quinolone subtemplates. Quinolones containing the amine-based side chain were selected as the pharmacophore for further modification, resulting in metabolically stable quinolones effective against multi drug resistant (MDR) Mtb. The lead compound, 42a (MTC420), displays acceptable antituberculosis activity (Mtb IC50 = 525 nM, Mtb Wayne IC50 = 76 nM, and MDR Mtb patient isolates IC50 = 140 nM) and favorable pharmacokinetic and toxicological profiles.