4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-(4-(morpholinosulfonyl)phenyl)quinoline-3-carbonitrile

• 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: 4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-(4-(morpholinosulfonyl)phenyl)quinoline-3-carbonitrile
• 英文别名: NEU-926；4-[3-Chloro-4-[(3-fluorophenyl)methoxy]anilino]-6-(4-morpholin-4-ylsulfonylphenyl)quinoline-3-carbonitrile；4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]-6-(4-morpholin-4-ylsulfonylphenyl)quinoline-3-carbonitrile
• 化学式: C₃₃H₂₆ClFN₄O₄S
• 分子量: 629.111
• InChiKey: NELMRQPMYXIQHF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  44
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-氯-4-硝基苯酚 在 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 、 氯化铵 、 锌 作用下， 以 乙醇 、 水 、 异丙醇 、 乙腈 为溶剂， 反应 8.0h， 生成 4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-(4-(morpholinosulfonyl)phenyl)quinoline-3-carbonitrile
  参考文献：
  名称：

  Protozoan Parasite Growth Inhibitors Discovered by Cross-Screening Yield Potent Scaffolds for Lead Discovery

  摘要：

  Tropical protozoal infections are a significant cause of morbidity and mortality worldwide; four in particular (human African trypanosomiasis (HAT), Chagas disease, cutaneous leishmaniasis, and malaria) have an estimated combined burden of over 87 million disability-adjusted life years. New drugs are needed for each of these diseases, Building on the previous identification of NEU-617 (1) as a potent and nontoxic inhibitor of proliferation for the HAT pathogen (Trypanosoma brucei), we have now tested this class of analogs against other protozoal species: T. cruzi (Chagas disease), Leishmania major (cutaneous leishmaniasis), and Plasmodium falciparum (malaria). Based on hits identified in this screening campaign, we describe the preparation of several replacements for the quinazoline scaffold and report these inhibitors' biological activities against these parasites. In doing this, we have identified several potent proliferation inhibitors for each pathogen, such as 4-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)quinoline-3-carbonitrile (NEU-924, 83) for T. cruzi and N-(3-chloro-4-((3-fluorobenzypoxy)phenyl)-7-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)cinnolin-4-amine (NEU-1017, 68) for L. major and P. falciparum.

  DOI：

  10.1021/acs.jmedchem.5b00515

文献信息

• Protozoan Parasite Growth Inhibitors Discovered by Cross-Screening Yield Potent Scaffolds for Lead Discovery
  作者：William Devine、Jennifer L. Woodring、Uma Swaminathan、Emanuele Amata、Gautam Patel、Jessey Erath、Norma E. Roncal、Patricia J. Lee、Susan E. Leed、Ana Rodriguez、Kojo Mensa-Wilmot、Richard J. Sciotti、Michael P. Pollastri

  DOI：10.1021/acs.jmedchem.5b00515

  日期：2015.7.23

  Tropical protozoal infections are a significant cause of morbidity and mortality worldwide; four in particular (human African trypanosomiasis (HAT), Chagas disease, cutaneous leishmaniasis, and malaria) have an estimated combined burden of over 87 million disability-adjusted life years. New drugs are needed for each of these diseases, Building on the previous identification of NEU-617 (1) as a potent and nontoxic inhibitor of proliferation for the HAT pathogen (Trypanosoma brucei), we have now tested this class of analogs against other protozoal species: T. cruzi (Chagas disease), Leishmania major (cutaneous leishmaniasis), and Plasmodium falciparum (malaria). Based on hits identified in this screening campaign, we describe the preparation of several replacements for the quinazoline scaffold and report these inhibitors' biological activities against these parasites. In doing this, we have identified several potent proliferation inhibitors for each pathogen, such as 4-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-6-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)quinoline-3-carbonitrile (NEU-924, 83) for T. cruzi and N-(3-chloro-4-((3-fluorobenzypoxy)phenyl)-7-(4-((4-methyl-1,4-diazepan-1-yl)sulfonyl)phenyl)cinnolin-4-amine (NEU-1017, 68) for L. major and P. falciparum.