6-chloro-7-methoxy-2-methyl-3-phenylquinolin-4(1H)-one | 1248347-00-3

• 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: 6-chloro-7-methoxy-2-methyl-3-phenylquinolin-4(1H)-one
• 英文别名: P4Q-95；6-chloro-7-methoxy-2-methyl-3-phenyl-1H-quinolin-4-one
• CAS: 1248347-00-3
• 化学式: C₁₇H₁₄ClNO₂
• 分子量: 299.757
• InChiKey: HKKWZNMLWCLVQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  diphenyliodonium hexafluorophosphate 在 potassium tert-butylate 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 24.05h， 生成 6-chloro-7-methoxy-2-methyl-3-phenylquinolin-4(1H)-one
  参考文献：
  名称：

  Metal-Free Arylation of Ethyl Acetoacetate with Hypervalent Diaryliodonium Salts: An Immediate Access to Diverse 3-Aryl-4(1H)-Quinolones

  摘要：

  A clean arylation protocol of ethyl acetoacetate was developed using hypervalent diaryliodonium salts under mild and metal-free conditions. The scope of the reaction, using symmetric and unsymmetric iodonium salts with varying sterics and electronics, was examined. Further, this method has been applied for the synthesis of antimalarial compound ELQ-300, which is currently in preclinical development.

  DOI：

  10.1021/jo5023958

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.
• Metal-Free Arylation of Ethyl Acetoacetate with Hypervalent Diaryliodonium Salts: An Immediate Access to Diverse 3-Aryl-4(1<i>H</i>)-Quinolones
  作者：Andrii Monastyrskyi、Niranjan K. Namelikonda、Roman Manetsch

  DOI：10.1021/jo5023958

  日期：2015.3.6

  A clean arylation protocol of ethyl acetoacetate was developed using hypervalent diaryliodonium salts under mild and metal-free conditions. The scope of the reaction, using symmetric and unsymmetric iodonium salts with varying sterics and electronics, was examined. Further, this method has been applied for the synthesis of antimalarial compound ELQ-300, which is currently in preclinical development.