(5S)-5-ethyl-19,19-difluoro-5-hydroxy-7,18,20-trioxa-11,24-diazahexacyclo[11.11.0.02,11.04,9.015,23.017,21]tetracosa-1(13),2,4(9),14,16,21,23-heptaene-6,10-dione

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: (5S)-5-ethyl-19,19-difluoro-5-hydroxy-7,18,20-trioxa-11,24-diazahexacyclo[11.11.0.02,11.04,9.015,23.017,21]tetracosa-1(13),2,4(9),14,16,21,23-heptaene-6,10-dione
• 化学式: C₂₁H₁₄F₂N₂O₆
• 分子量: 428.349
• InChiKey: KMBMVMQTZOEGAD-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  31
• 可旋转键数：
  1
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  98.2
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2,2-二氟-1,3-苯并二恶茂-5-甲醛 在 ammonium hydroxide 、 硝酸 、 对甲苯磺酸 、 iron(II) sulfate 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 溶剂黄146 、 乙酸乙酯 、 甲苯 为溶剂， 反应 19.08h， 生成 (5S)-5-ethyl-19,19-difluoro-5-hydroxy-7,18,20-trioxa-11,24-diazahexacyclo[11.11.0.02,11.04,9.015,23.017,21]tetracosa-1(13),2,4(9),14,16,21,23-heptaene-6,10-dione
  参考文献：
  名称：

  Analysis of stereoelectronic properties of camptothecin analogues in relation to biological activity

  摘要：

  Camptothecin and four of its 10,11-methylenedioxy analogues were examined for their activity against the pathogenic protozoan Leishmania donovani in vitro. The methylenedioxy analogues were 36- to 180-fold more potent than the parent camptothecin, possessing IC50 values ranging from 160 to 32 nM against the parasite. Our finding that the methylenedioxy camptothecins possess greater activity than camptothecin, which is also the case for other cell types and for the generation of cleavable complex in the presence of DNA and purified mammalian topoisomerase I, prompted us to examine the molecular features of camptothecin and methylenedioxy camptothecin analogues. A delocalization of positive potential was observed in the methylenedioxy camptothecin analogues, which could increase the affinity of these molecules for DNA. In addition, geometrical and electronic differences between the E ring of camptothecin and its methylenedioxy analogues were noted. One or both of these factors may contribute to the superior biological activity of the methylenedioxy camptothecin analogues. Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(00)00111-5

文献信息

• Analysis of stereoelectronic properties of camptothecin analogues in relation to biological activity
  作者：Karl A. Werbovetz、Apurba K. Bhattacharjee、James J. Brendle、John P. Scovill

  DOI：10.1016/s0968-0896(00)00111-5

  日期：2000.7

  Camptothecin and four of its 10,11-methylenedioxy analogues were examined for their activity against the pathogenic protozoan Leishmania donovani in vitro. The methylenedioxy analogues were 36- to 180-fold more potent than the parent camptothecin, possessing IC50 values ranging from 160 to 32 nM against the parasite. Our finding that the methylenedioxy camptothecins possess greater activity than camptothecin, which is also the case for other cell types and for the generation of cleavable complex in the presence of DNA and purified mammalian topoisomerase I, prompted us to examine the molecular features of camptothecin and methylenedioxy camptothecin analogues. A delocalization of positive potential was observed in the methylenedioxy camptothecin analogues, which could increase the affinity of these molecules for DNA. In addition, geometrical and electronic differences between the E ring of camptothecin and its methylenedioxy analogues were noted. One or both of these factors may contribute to the superior biological activity of the methylenedioxy camptothecin analogues. Published by Elsevier Science Ltd.