1-ethyl-N-(4-methoxybenzyl)-4-oxo-7-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide | 1092179-47-9

• 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-ethyl-N-(4-methoxybenzyl)-4-oxo-7-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide
• 英文别名: 1-ethyl-N-[(4-methoxyphenyl)methyl]-4-oxo-7-(trifluoromethyl)quinoline-3-carboxamide
• CAS: 1092179-47-9
• 化学式: C₂₁H₁₉F₃N₂O₃
• 分子量: 404.389
• InChiKey: JKUBZGCOTIXBCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-ethyl-4-oxo-7-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxylic acid 在 N-甲基吗啉 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-ethyl-N-(4-methoxybenzyl)-4-oxo-7-(trifluoromethyl)-1,4-dihydroquinoline-3-carboxamide
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of New Quinolone-Type Molecules against Trypanosoma brucei

  摘要：

  Human African trypanosomiasis (HAT) or sleeping sickness is caused by two subspecies of Trypanosoma brucei, Trypanosoma brucei gambiense, and Trypanosoma brucei rhodesiense and is one of Africa's old plagues. It causes a huge number of infections and cases of death per year because, apart from limited access to health services, only inefficient chemotherapy is available. Since it was reported that quinolones such as ciprofloxacin show antitrypanosomal activity, a novel quinolone-type library was synthesized and tested. The biological evaluation illustrated that 4-quinolones with a benzylamide function in position 3 and cyclic or acyclic amines in position 7 exhibit high antitrypanosomal activity. Structure-activity relationships (SAR) are established to identify essential structural elements. This analysis led to lead structure 29, which exhibits promising in vitro activity against T. b. brucei (IC50 = 47 nM) and T. b. rhodesiense (IC50 = 9 nM) combined with low cytotoxicity against macrophages J774.1. Screening for morphological changes of trypanosomes treated with compounds 19 and 29 suggested differences in the morphology of mitochondria of treated cells compared to those of untreated cells. Segregation of the kinetoplast is hampered in trypanosomes treated with these compounds; however, topoisomerase II is probably not the main drug target.

  DOI：

  10.1021/jm101439s

文献信息

• A Small-Molecule Inhibitor of Nipah Virus Envelope Protein-Mediated Membrane Fusion
  作者：Sabine Niedermeier、Katrin Singethan、Sebastian G. Rohrer、Magnus Matz、Markus Kossner、Sandra Diederich、Andrea Maisner、Jens Schmitz、Georg Hiltensperger、Knut Baumann、Ulrike Holzgrabe、Jürgen Schneider-Schaulies

  DOI：10.1021/jm900411s

  日期：2009.7.23

  Nipah virus (NiV), a highly pathogenic paramyxovirus. causes respiratory disease in pigs and severe febrile encephalitis in humans with high mortality rates. On the basis of the structural similarity of viral fusion (F) proteins within the family Paramyxoviridae, we designed and tested 18 quinolone derivatives in a NiV and measles virus (MV) envelope protein-based fusion assay beside evaluation of cytotoxicity. We found five compounds successfully inhibiting NiV envelope protein-induced cell fusion. The most active molecules (19 and 20), which also inhibit the syncytium formation induced by infectious NiV and show a low cytotoxicity in Vero cells, represent a promising lead quinolone-type compound structure. Molecular modeling indicated that compound 19 fits well into a particular protein cavity present on the NiV F protein that is important for the fusion process.
• Synthesis and Structure–Activity Relationships of New Quinolone-Type Molecules against Trypanosoma brucei
  作者：Georg Hiltensperger、Nicola G. Jones、Sabine Niedermeier、August Stich、Marcel Kaiser、Jamin Jung、Sebastian Puhl、Alexander Damme、Holger Braunschweig、Lorenz Meinel、Markus Engstler、Ulrike Holzgrabe

  DOI：10.1021/jm101439s

  日期：2012.3.22

  Human African trypanosomiasis (HAT) or sleeping sickness is caused by two subspecies of Trypanosoma brucei, Trypanosoma brucei gambiense, and Trypanosoma brucei rhodesiense and is one of Africa's old plagues. It causes a huge number of infections and cases of death per year because, apart from limited access to health services, only inefficient chemotherapy is available. Since it was reported that quinolones such as ciprofloxacin show antitrypanosomal activity, a novel quinolone-type library was synthesized and tested. The biological evaluation illustrated that 4-quinolones with a benzylamide function in position 3 and cyclic or acyclic amines in position 7 exhibit high antitrypanosomal activity. Structure-activity relationships (SAR) are established to identify essential structural elements. This analysis led to lead structure 29, which exhibits promising in vitro activity against T. b. brucei (IC50 = 47 nM) and T. b. rhodesiense (IC50 = 9 nM) combined with low cytotoxicity against macrophages J774.1. Screening for morphological changes of trypanosomes treated with compounds 19 and 29 suggested differences in the morphology of mitochondria of treated cells compared to those of untreated cells. Segregation of the kinetoplast is hampered in trypanosomes treated with these compounds; however, topoisomerase II is probably not the main drug target.