2-chloro-5-methoxy-N-(pyridin-2-yl)-acridone-4-carboxamide | 1221746-58-2

• 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: 2-chloro-5-methoxy-N-(pyridin-2-yl)-acridone-4-carboxamide
• 英文别名: 2-chloro-5-methoxy-9-oxo-N-(2-pyridyl)-10H-acridine-4-carboxamide；2-chloro-5-methoxy-9-oxo-N-pyridin-2-yl-10H-acridine-4-carboxamide
• CAS: 1221746-58-2
• 化学式: C₂₀H₁₄ClN₃O₃
• 分子量: 379.802
• InChiKey: KDNNHRBPAAZBDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  80.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-氨基吡啶 、 2-chloro-5-methoxyacridone-4-carboxylic acid 在 吡啶 、 氯化亚砜 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 4.0h， 以52%的产率得到2-chloro-5-methoxy-N-(pyridin-2-yl)-acridone-4-carboxamide
  参考文献：
  名称：

  Synthesis of New Acridone Derivatives, Inhibitors of NS3 Helicase, Which Efficiently and Specifically Inhibit Subgenomic HCV Replication

  摘要：

  A new goup of acridone derivatives, obtained by reaction of acridone-4-carboxylic acid derivatives with aromatic amines, was tested to determine the inhibitory properties toward the NS3 helicase of hepatitis C virus (HCV). Six compounds inhibited the NS3 helicase at low concentrations (IC(50) from 1.5 to 20 mu M). The acridone derivatives probably act via intercalation into double-stranded nucleic acids with a strong specificity for double-stranded RNA, although an interaction with the enzyme cannot be excluded. Testing in the subgenomic HCV replicon system revealed that compounds 10 and 13 are efficient RNA replication inhibitors, with EC(50) of 3.5 and 1 mu M and therapeutic indexes of > 28 and 20, respectively. Compound 16, with EC(50) < 1 mu M and TI > 1000, is extremely specific and practically noncytotoxic at the concentrations tested, proving that the acridone derivatives may be regarded as potential antiviral agents. Although the mechanism of action of 16 in the replicon system remains unclear, it is the key lead compound for further development of anti-HCV drugs.

  DOI：

  10.1021/jm901741p

文献信息

• Synthesis of New Acridone Derivatives, Inhibitors of NS3 Helicase, Which Efficiently and Specifically Inhibit Subgenomic HCV Replication
  作者：Anna Stankiewicz-Drogoń、Bernd Dörner、Thomas Erker、Anna M. Boguszewska-Chachulska

  DOI：10.1021/jm901741p

  日期：2010.4.22

  A new goup of acridone derivatives, obtained by reaction of acridone-4-carboxylic acid derivatives with aromatic amines, was tested to determine the inhibitory properties toward the NS3 helicase of hepatitis C virus (HCV). Six compounds inhibited the NS3 helicase at low concentrations (IC(50) from 1.5 to 20 mu M). The acridone derivatives probably act via intercalation into double-stranded nucleic acids with a strong specificity for double-stranded RNA, although an interaction with the enzyme cannot be excluded. Testing in the subgenomic HCV replicon system revealed that compounds 10 and 13 are efficient RNA replication inhibitors, with EC(50) of 3.5 and 1 mu M and therapeutic indexes of > 28 and 20, respectively. Compound 16, with EC(50) < 1 mu M and TI > 1000, is extremely specific and practically noncytotoxic at the concentrations tested, proving that the acridone derivatives may be regarded as potential antiviral agents. Although the mechanism of action of 16 in the replicon system remains unclear, it is the key lead compound for further development of anti-HCV drugs.