7-Amino-1,3-dimethoxy-10-methyl-6-(4-pyridin-2-yl-piperazin-1-yl)-10H-acridin-9-one | 887776-32-1

• 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: 7-Amino-1,3-dimethoxy-10-methyl-6-(4-pyridin-2-yl-piperazin-1-yl)-10H-acridin-9-one
• 英文别名: 7-Amino-1,3-dimethoxy-10-methyl-6-[4-(2-pyridyl)piperazin-1-yl]acridin-9-one；7-amino-1,3-dimethoxy-10-methyl-6-(4-pyridin-2-ylpiperazin-1-yl)acridin-9-one
• CAS: 887776-32-1
• 化学式: C₂₅H₂₇N₅O₃
• 分子量: 445.521
• InChiKey: GCFOBPABVOEWHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  7-Amino-1,3-dimethoxy-10-methyl-6-(4-pyridin-2-yl-piperazin-1-yl)-10H-acridin-9-one 在 盐酸 、 sodium nitrite 、 氟硼酸钠 作用下， 以 水 为溶剂， 反应 1.0h， 生成 6,8-dimethoxy-10-methyl-9-oxo-3-[4-(2-pyridinyl)-1-piperazinyl]-9,10-dihydro-2-acridinediazonium tetrafluoroborate
  参考文献：
  名称：

  Inhibition of Subgenomic Hepatitis C Virus RNA Replication by Acridone Derivatives: Identification of an NS3 Helicase Inhibitor

  摘要：

  We report the synthesis and structure - activity relationship (SAR) of a large series of acridones and acridone-fragment derivatives designed on the basis of the selective antihepatitis C virus (HCV) activity shown by acridone 2, previously studied as a potential antibovine viral diarrhea virus (BVDV) compound. The evaluation of their ability to inhibit the HCV replication in Huh-5-2 cells led to the identification of new, selective inhibitors. This indicates that the acridone skeleton, when properly functionalized, is a suitable scaffold to obtain potential anti-HCV agents. Interestingly, during identification of possible cellular and viral targets, it was discovered that compound 23 exerts inhibitory activity on the HCV NS3 helicase, a very promising target for the development of anti-HCV drugs.

  DOI：

  10.1021/jm801608u
• 作为产物：
  描述：

  1-(2-吡啶基)哌嗪 在 盐酸 、 tin(ll) chloride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.0h， 生成 7-Amino-1,3-dimethoxy-10-methyl-6-(4-pyridin-2-yl-piperazin-1-yl)-10H-acridin-9-one
  参考文献：
  名称：

  Synthesis and Anti-BVDV Activity of Acridones As New Potential Antiviral Agents

  摘要：

  In this study we report the design, synthesis, and activity against bovine viral diarrhea virus (BVDV) of a novel series of acridone derivatives. BVDV is responsible for major losses in cattle. The virus is also considered to be a valuable surrogate for the hepatitis C virus (HCV) in antiviral drug studies. Some of the synthesized acridones elicited selective anti-BVDV activity with EC50 values ranging from 0.4 to 4 mu g/mL and were not cytotoxic at concentrations that were 25- to 200-fold higher (CC50 > 100 mu g/mL). It was proven that the most potent acridone derivative 10 was able to not only protect cells from virus-induced cytopathic effect but also reduce the production of infectious virus and extracellular viral RNA. Furthermore, compound 10, as well as a number of other analogues, inhibited HCV replication to some extent. However, there was no direct correlation between anti-BVDV and anti-HCV activity. Thus, the acridone scaffold, when appropriately functionalized, can yield compounds with selective activity against pestiviruses and related viruses such as the HCV.

  DOI：

  10.1021/jm051250z

文献信息

• Inhibition of Subgenomic Hepatitis C Virus RNA Replication by Acridone Derivatives: Identification of an NS3 Helicase Inhibitor
  作者：Giuseppe Manfroni、Jan Paeshuyse、Serena Massari、Samantha Zanoli、Barbara Gatto、Giovanni Maga、Oriana Tabarrini、Violetta Cecchetti、Arnaldo Fravolini、Johan Neyts

  DOI：10.1021/jm801608u

  日期：2009.5.28

  We report the synthesis and structure - activity relationship (SAR) of a large series of acridones and acridone-fragment derivatives designed on the basis of the selective antihepatitis C virus (HCV) activity shown by acridone 2, previously studied as a potential antibovine viral diarrhea virus (BVDV) compound. The evaluation of their ability to inhibit the HCV replication in Huh-5-2 cells led to the identification of new, selective inhibitors. This indicates that the acridone skeleton, when properly functionalized, is a suitable scaffold to obtain potential anti-HCV agents. Interestingly, during identification of possible cellular and viral targets, it was discovered that compound 23 exerts inhibitory activity on the HCV NS3 helicase, a very promising target for the development of anti-HCV drugs.
• Synthesis and Anti-BVDV Activity of Acridones As New Potential Antiviral Agents
  作者：Oriana Tabarrini、Giuseppe Manfroni、Arnaldo Fravolini、Violetta Cecchetti、Stefano Sabatini、Erik De Clercq、Jef Rozenski、Bruno Canard、Hélène Dutartre、Jan Paeshuyse、Johan Neyts

  DOI：10.1021/jm051250z

  日期：2006.4.1

  In this study we report the design, synthesis, and activity against bovine viral diarrhea virus (BVDV) of a novel series of acridone derivatives. BVDV is responsible for major losses in cattle. The virus is also considered to be a valuable surrogate for the hepatitis C virus (HCV) in antiviral drug studies. Some of the synthesized acridones elicited selective anti-BVDV activity with EC50 values ranging from 0.4 to 4 mu g/mL and were not cytotoxic at concentrations that were 25- to 200-fold higher (CC50 > 100 mu g/mL). It was proven that the most potent acridone derivative 10 was able to not only protect cells from virus-induced cytopathic effect but also reduce the production of infectious virus and extracellular viral RNA. Furthermore, compound 10, as well as a number of other analogues, inhibited HCV replication to some extent. However, there was no direct correlation between anti-BVDV and anti-HCV activity. Thus, the acridone scaffold, when appropriately functionalized, can yield compounds with selective activity against pestiviruses and related viruses such as the HCV.