N-(pentafluoropropionyl)adriamycin | 80242-51-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: N-(pentafluoropropionyl)adriamycin
• 英文别名: 2,2,3,3,3-pentafluoro-N-[(2S,3S,4S,6R)-3-hydroxy-2-methyl-6-[[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]oxan-4-yl]propanamide
• CAS: 80242-51-9
• 化学式: C₃₀H₂₈F₅NO₁₂
• 分子量: 689.544
• InChiKey: PXKNMUUIFRQWIN-XUKKXQNXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  48
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  209
• 氢给体数：
  6
• 氢受体数：
  17

反应信息

• 作为产物：
  描述：

  阿霉素 、 五氟丙酸酐 在 吡啶 作用下， 以 乙醚 为溶剂， 反应 0.33h， 以59%的产率得到N-(pentafluoropropionyl)adriamycin
  参考文献：
  名称：

  Adriamycin analogs. Preparation and biological evaluation of some N-perfluoroacyl analogs of daunorubicin, adriamycin, and N-(trifluoroacetyl)adriamycin 14-valerate and their 9,10-anhydro derivatives

  摘要：

  The experimental and clinical antitumor activity, as well as the low toxicity, of N-(trifluoroacetyl)adriamycin 14-valerate (AD 32), a non-DNA binding anthracycline analogue, has led us to prepare and evaluate several N-perfluoroacyl analogues of daunorubicin, adriamycin, and N-(trifluoroacetyl)adriamycin 14-valerate. Target compounds were prepared by reaction of the appropriate perfluoroacyl anhydride with daunorubicin in chloroform-ether, with adriamycin in cold pyridine, and with adriamycin 14-valerate in ethyl acetate. In connection with this work, it was found that reaction of perfluoroacyl anhydrides with N-acylated or N-unsubstituted anthracyclines in pyridine at room temperature afforded with ease and in good yield the corresponding 9,10-anhydro-N-acylated derivatives. A number of products showed good to highly significant antitumor activity in vivo against the murine P388 leukemia system. However, the lack of in vivo antitumor activity of the pentafluoropropionyl and heptafluorobutyryl analogues of N-(trifluoroacetyl)adriamycin 14-valerate is noteworthy. The results continue to show that non-DNA binding anthracycline analogues can exhibit in vivo antitumor activity. Loss of the anthracycline 9-carbinol function by dehydration leads to reduction of biological activity as compared to the parent compound.

  DOI：

  10.1021/jm00344a019

文献信息

• Adriamycin analogs. Preparation and biological evaluation of some N-perfluoroacyl analogs of daunorubicin, adriamycin, and N-(trifluoroacetyl)adriamycin 14-valerate and their 9,10-anhydro derivatives
  作者：Mervyn Israel、Gopalakrishnan Potti

  DOI：10.1021/jm00344a019

  日期：1982.2

  The experimental and clinical antitumor activity, as well as the low toxicity, of N-(trifluoroacetyl)adriamycin 14-valerate (AD 32), a non-DNA binding anthracycline analogue, has led us to prepare and evaluate several N-perfluoroacyl analogues of daunorubicin, adriamycin, and N-(trifluoroacetyl)adriamycin 14-valerate. Target compounds were prepared by reaction of the appropriate perfluoroacyl anhydride with daunorubicin in chloroform-ether, with adriamycin in cold pyridine, and with adriamycin 14-valerate in ethyl acetate. In connection with this work, it was found that reaction of perfluoroacyl anhydrides with N-acylated or N-unsubstituted anthracyclines in pyridine at room temperature afforded with ease and in good yield the corresponding 9,10-anhydro-N-acylated derivatives. A number of products showed good to highly significant antitumor activity in vivo against the murine P388 leukemia system. However, the lack of in vivo antitumor activity of the pentafluoropropionyl and heptafluorobutyryl analogues of N-(trifluoroacetyl)adriamycin 14-valerate is noteworthy. The results continue to show that non-DNA binding anthracycline analogues can exhibit in vivo antitumor activity. Loss of the anthracycline 9-carbinol function by dehydration leads to reduction of biological activity as compared to the parent compound.