4-(6-chloro-7-methoxy-2-methyl-4-oxo-1,4-dihydroquinolin-3-yl)benzaldehyde

• 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-(6-chloro-7-methoxy-2-methyl-4-oxo-1,4-dihydroquinolin-3-yl)benzaldehyde
• 英文别名: 4-(6-chloro-7-methoxy-2-methyl-4-oxo-1H-quinolin-3-yl)benzaldehyde
• 化学式: C₁₈H₁₄ClNO₃
• 分子量: 327.767
• InChiKey: BLSUDWIRNHOKPA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-甲氧基-4-氯苯胺 在 四(三苯基膦)钯 、 碘 、 sodium carbonate 、 溶剂黄146 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 18.2h， 生成 4-(6-chloro-7-methoxy-2-methyl-4-oxo-1,4-dihydroquinolin-3-yl)benzaldehyde
  参考文献：
  名称：

  Orally Bioavailable 6-Chloro-7-methoxy-4(1H)-quinolones Efficacious against Multiple Stages of Plasmodium

  摘要：

  The continued proliferation of malaria throughout temperate and tropical regions of the world has promoted a push for more efficacious treatments to combat the disease. Unfortunately, more recent remedies such as artemisinin combination therapies have been rendered less effective due to developing parasite resistance, and new drugs are required that target the parasite in the liver to support the disease elimination efforts. Research was initiated to revisit antimalarials developed in the 1940s and 1960s that were deemed unsuitable for use as therapeutic agents as a result of poor understanding of both physicochemical properties and parasitology. Structure-activity and structure-property relationship studies were conducted to generate a set of compounds with the general 6-chloro-7-methoxy-2-methyl-4(1H)-quinolone scaffold which were substituted at the 3-position with a variety of phenyl moieties possessing various properties. Extensive physicochemical evaluation of the quinolone series was carried out to downselect the most promising 4(1H)-quinolones, 7, 62, 66, and 67, which possessed low-nanomolar EC50 values against W2 and TM90-C2B as well as improved microsomal stability. Additionally, in vivo Thompson test results using Plasmodium berghei in mice showed that these 4(1H)-quinolones were efficacious for the reduction of parasitemia at >99% after 6 days.

  DOI：

  10.1021/jm500942v

文献信息

• Orally Bioavailable 6-Chloro-7-methoxy-4(1<i>H</i>)-quinolones Efficacious against Multiple Stages of <i>Plasmodium</i>
  作者：R. Matthew Cross、David L. Flanigan、Andrii Monastyrskyi、Alexis N. LaCrue、Fabián E. Sáenz、Jordany R. Maignan、Tina S. Mutka、Karen L. White、David M. Shackleford、Ian Bathurst、Frank R Fronczek、Lukasz Wojtas、Wayne C. Guida、Susan A. Charman、Jeremy N. Burrows、Dennis E. Kyle、Roman Manetsch

  DOI：10.1021/jm500942v

  日期：2014.11.13

  The continued proliferation of malaria throughout temperate and tropical regions of the world has promoted a push for more efficacious treatments to combat the disease. Unfortunately, more recent remedies such as artemisinin combination therapies have been rendered less effective due to developing parasite resistance, and new drugs are required that target the parasite in the liver to support the disease elimination efforts. Research was initiated to revisit antimalarials developed in the 1940s and 1960s that were deemed unsuitable for use as therapeutic agents as a result of poor understanding of both physicochemical properties and parasitology. Structure-activity and structure-property relationship studies were conducted to generate a set of compounds with the general 6-chloro-7-methoxy-2-methyl-4(1H)-quinolone scaffold which were substituted at the 3-position with a variety of phenyl moieties possessing various properties. Extensive physicochemical evaluation of the quinolone series was carried out to downselect the most promising 4(1H)-quinolones, 7, 62, 66, and 67, which possessed low-nanomolar EC50 values against W2 and TM90-C2B as well as improved microsomal stability. Additionally, in vivo Thompson test results using Plasmodium berghei in mice showed that these 4(1H)-quinolones were efficacious for the reduction of parasitemia at >99% after 6 days.