(10R,15R,16R)-10-(4-hydroxy-3,5-dimethoxyphenyl)-16-methoxy-13-oxa-8,11-diazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-12-one | 177020-27-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (10R,15R,16R)-10-(4-hydroxy-3,5-dimethoxyphenyl)-16-methoxy-13-oxa-8,11-diazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-12-one
• CAS: 177020-27-8
• 化学式: C₂₂H₂₂N₂O₆
• 分子量: 410.426
• InChiKey: FPDFXFCUSADUQJ-MMACOIQUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  93.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (10R,15R,16R)-10-(4-hydroxy-3,5-dimethoxyphenyl)-16-methoxy-13-oxa-8,11-diazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-12-one 在 palladium on activated charcoal 4 A molecular sieve 、 TEA 、 三氟化硼乙醚 、 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (3aS,4R,10R)-10-(4-Hydroxy-3,5-dimethoxy-phenyl)-4-(4-hydroxy-3,5-dimethoxy-phenylamino)-3a,4,9,10-tetrahydro-3H-2-oxa-9,10a-diaza-cyclopenta[b]fluoren-1-one
  参考文献：
  名称：

  Inhibition of DNA Topoisomerase II by Azaelliptitoxins Functionalized in the Variable Substituent Domain

  摘要：

  A series of novel C-11-substituted derivatives of azaelliptitoxin (azatoxin) have been synthesized and tested for their inhibitory activity against human DNA topoisomerase II. Incorporation of a C-11 polyamine pr amine resulted in an increase in the intercalation properties of the drug and a decrease of topoisomerase II activity. The structure-activity relationship (SAR) profile of the nonintercalating C-11 anilino azatoxin class follows the SAR of the (anilino)acridine family. 11-(4-Cyanoanilino)azatoxin (14) was found to be the most active analog in this series, exhibiting similar to 10-fold higher activity than azatoxin 12 and etoposide.

  DOI：

  10.1021/jm9508806
• 作为产物：
  描述：

  丁香醛 在 对甲苯磺酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (10R,15R,16R)-10-(4-hydroxy-3,5-dimethoxyphenyl)-16-methoxy-13-oxa-8,11-diazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-12-one
  参考文献：
  名称：

  Inhibition of DNA Topoisomerase II by Azaelliptitoxins Functionalized in the Variable Substituent Domain

  摘要：

  A series of novel C-11-substituted derivatives of azaelliptitoxin (azatoxin) have been synthesized and tested for their inhibitory activity against human DNA topoisomerase II. Incorporation of a C-11 polyamine pr amine resulted in an increase in the intercalation properties of the drug and a decrease of topoisomerase II activity. The structure-activity relationship (SAR) profile of the nonintercalating C-11 anilino azatoxin class follows the SAR of the (anilino)acridine family. 11-(4-Cyanoanilino)azatoxin (14) was found to be the most active analog in this series, exhibiting similar to 10-fold higher activity than azatoxin 12 and etoposide.

  DOI：

  10.1021/jm9508806

文献信息

• Inhibition of DNA Topoisomerase II by Azaelliptitoxins Functionalized in the Variable Substituent Domain
  作者：Jetze J. Tepe、Jose S. Madalengoitia、Kelli M. Slunt、Karl W. Werbovetz、P. Grant Spoors、Timothy L. Macdonald

  DOI：10.1021/jm9508806

  日期：1996.1.1

  A series of novel C-11-substituted derivatives of azaelliptitoxin (azatoxin) have been synthesized and tested for their inhibitory activity against human DNA topoisomerase II. Incorporation of a C-11 polyamine pr amine resulted in an increase in the intercalation properties of the drug and a decrease of topoisomerase II activity. The structure-activity relationship (SAR) profile of the nonintercalating C-11 anilino azatoxin class follows the SAR of the (anilino)acridine family. 11-(4-Cyanoanilino)azatoxin (14) was found to be the most active analog in this series, exhibiting similar to 10-fold higher activity than azatoxin 12 and etoposide.