(5R,11R,11aS)-4,5,11,11a-tetrahydro-5-[3,5-dimethoxy-4-(carbobenzoxyoxy)phenyl]-11-[3-methoxy-4-(carbobenzoxyoxy)anilino]-1H,6H-oxazolo[3',4':1,6]pyrido[3,4-b]indol-3-one | 176915-13-2

• 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: (5R,11R,11aS)-4,5,11,11a-tetrahydro-5-[3,5-dimethoxy-4-(carbobenzoxyoxy)phenyl]-11-[3-methoxy-4-(carbobenzoxyoxy)anilino]-1H,6H-oxazolo[3',4':1,6]pyrido[3,4-b]indol-3-one
• 英文别名: benzyl [2,6-dimethoxy-4-[(10R,15S,16R)-16-(3-methoxy-4-phenylmethoxycarbonyloxyanilino)-12-oxo-13-oxa-8,11-diazatetracyclo[7.7.0.02,7.011,15]hexadeca-1(9),2,4,6-tetraen-10-yl]phenyl] carbonate
• CAS: 176915-13-2
• 化学式: C₄₄H₃₉N₃O₁₁
• 分子量: 785.807
• InChiKey: IWTWVNIEQQIUQM-HHMFQWOISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  58
• 可旋转键数：
  16
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  156
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (5R,11R,11aS)-4,5,11,11a-tetrahydro-5-[3,5-dimethoxy-4-(carbobenzoxyoxy)phenyl]-11-[3-methoxy-4-(carbobenzoxyoxy)anilino]-1H,6H-oxazolo[3',4':1,6]pyrido[3,4-b]indol-3-one 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 以81%的产率得到(10R,15S,16R)-10-(4-hydroxy-3,5-dimethoxyphenyl)-16-(4-hydroxy-3-methoxyanilino)-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
• 作为产物：
  描述：

  S-4-(1H-吲哚-3-甲基)-2-噁唑烷酮 在 4 A molecular sieve 、 TEA 、 三氟化硼乙醚 、 对甲苯磺酸 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 32.5h， 生成 (5R,11R,11aS)-4,5,11,11a-tetrahydro-5-[3,5-dimethoxy-4-(carbobenzoxyoxy)phenyl]-11-[3-methoxy-4-(carbobenzoxyoxy)anilino]-1H,6H-oxazolo[3',4':1,6]pyrido[3,4-b]indol-3-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.