5-Chloro-1-hydroxy-3-methoxy-10-methyl-10H-acridin-9-one

• 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: 5-Chloro-1-hydroxy-3-methoxy-10-methyl-10H-acridin-9-one
• 英文别名: 5-Chloro-1-hydroxy-3-methoxy-10-methyl-acridin-9-one；5-chloro-1-hydroxy-3-methoxy-10-methylacridin-9-one
• 化学式: C₁₅H₁₂ClNO₃
• 分子量: 289.718
• InChiKey: WIOACTBZYKLOBS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-Chloro-1-hydroxy-3-methoxy-10-methyl-10H-acridin-9-one 在 氢溴酸 作用下， 反应 18.0h， 以76%的产率得到5-Chloro-1,3-dihydroxy-10-methyl-10H-acridin-9-one
  参考文献：
  名称：

  Anti-Herpes Simplex Virus Activity of Substituted 1-Hydroxyacridones

  摘要：

  5-Chloro-1,3-dihydroxyacridone, 1, is a potent and selective inhibitor of Herpes Simplex Virus Type-1 (HSV-1).(1) Substituted 1,3-dihydroxyacridones represent a new class of nonnucleoside HSV-1 inhibitors, and biochemical studies indicate a novel mechanism of action for 1, although the target is not yet defined.(2) With the goal of lead optimization, analogues of 1 were synthesized in an effort to describe the structure-activity relationships between 1 and its hypothetical binding site. Modifications of key functional groups led to the identity of several features of I that were important for activity. In the process, a more expedient and reliable synthesis of 1 and its analogues was developed. Analogues were evaluated against HSV-1 and HSV-2 using a viral plaque-elimination assay for viral inhibition of HSV-1 and HSV-2, and effects on replication of the host cell were also measured in order to assess a therapeutic index (TI) of selectivity. Several new analogues with significant antiviral activity were identified, including 5-methoxy-1,3-dihydroxyacridone (11), which inhibits replication of several HSV-2 strains with a mean ED50 of 0.7 muM and a TI range of 25-60-fold.

  DOI：

  10.1021/jm030206l
• 作为产物：
  描述：

  5-chloro-1,3-dihydroxyacridone 、 碘甲烷 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以70%的产率得到5-Chloro-1-hydroxy-3-methoxy-10-methyl-10H-acridin-9-one
  参考文献：
  名称：

  Anti-Herpes Simplex Virus Activity of Substituted 1-Hydroxyacridones

  摘要：

  5-Chloro-1,3-dihydroxyacridone, 1, is a potent and selective inhibitor of Herpes Simplex Virus Type-1 (HSV-1).(1) Substituted 1,3-dihydroxyacridones represent a new class of nonnucleoside HSV-1 inhibitors, and biochemical studies indicate a novel mechanism of action for 1, although the target is not yet defined.(2) With the goal of lead optimization, analogues of 1 were synthesized in an effort to describe the structure-activity relationships between 1 and its hypothetical binding site. Modifications of key functional groups led to the identity of several features of I that were important for activity. In the process, a more expedient and reliable synthesis of 1 and its analogues was developed. Analogues were evaluated against HSV-1 and HSV-2 using a viral plaque-elimination assay for viral inhibition of HSV-1 and HSV-2, and effects on replication of the host cell were also measured in order to assess a therapeutic index (TI) of selectivity. Several new analogues with significant antiviral activity were identified, including 5-methoxy-1,3-dihydroxyacridone (11), which inhibits replication of several HSV-2 strains with a mean ED50 of 0.7 muM and a TI range of 25-60-fold.

  DOI：

  10.1021/jm030206l

文献信息

• Anti-Herpes Simplex Virus Activity of Substituted 1-Hydroxyacridones
  作者：Christopher T. Lowden、Kenneth F. Bastow

  DOI：10.1021/jm030206l

  日期：2003.11.1

  5-Chloro-1,3-dihydroxyacridone, 1, is a potent and selective inhibitor of Herpes Simplex Virus Type-1 (HSV-1).(1) Substituted 1,3-dihydroxyacridones represent a new class of nonnucleoside HSV-1 inhibitors, and biochemical studies indicate a novel mechanism of action for 1, although the target is not yet defined.(2) With the goal of lead optimization, analogues of 1 were synthesized in an effort to describe the structure-activity relationships between 1 and its hypothetical binding site. Modifications of key functional groups led to the identity of several features of I that were important for activity. In the process, a more expedient and reliable synthesis of 1 and its analogues was developed. Analogues were evaluated against HSV-1 and HSV-2 using a viral plaque-elimination assay for viral inhibition of HSV-1 and HSV-2, and effects on replication of the host cell were also measured in order to assess a therapeutic index (TI) of selectivity. Several new analogues with significant antiviral activity were identified, including 5-methoxy-1,3-dihydroxyacridone (11), which inhibits replication of several HSV-2 strains with a mean ED50 of 0.7 muM and a TI range of 25-60-fold.