7-[4-O-(2,6-dideoxy-α-L-arabino-hexopyranosyl)-3-azido-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl]daunorubicinone

• 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: 7-[4-O-(2,6-dideoxy-α-L-arabino-hexopyranosyl)-3-azido-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl]daunorubicinone
• 英文别名: (7S,9S)-9-acetyl-7-[(2R,4S,5S,6S)-4-azido-5-[(2S,4S,5R,6S)-4,5-dihydroxy-6-methyloxan-2-yl]oxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione
• 化学式: C₃₃H₃₇N₃O₁₃
• 分子量: 683.669
• InChiKey: AYMUZTGNSZQHQK-NIGIIATCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  49
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  213
• 氢给体数：
  5
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  柔红霉素 盐酸盐 在 sodium hydroxide 、 六氟磷酸银 、 triflic azide 、 水 、 potassium carbonate 、 copper(II) sulfate 、 2,4,6-三叔丁基嘧啶 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 7-[4-O-(2,6-dideoxy-α-L-arabino-hexopyranosyl)-3-azido-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl]daunorubicinone
  参考文献：
  名称：

  WO2006/124720

  摘要：

  公开号：

文献信息

• WO2006/124720
  申请人：——

  公开号：——

  公开（公告）日：——
• Syntheses and Biological Activities of 3‘-Azido Disaccharide Analogues of Daunorubicin against Drug-Resistant Leukemia
  作者：Guisheng Zhang、Lanyan Fang、Lizhi Zhu、Yanqiang Zhong、Peng George Wang、Duxin Sun

  DOI：10.1021/jm050916m

  日期：2006.3.1

  Anthracyclines, such as daunorubicin (DNR) and doxorubicin (Dox), are widely used for cancer therapy but are limited by drug resistance and cardiotoxicity. To overcome drug resistance, we synthesized a novel class of disaccharide analogues of DNR against drug-resistant leukemia. In these disaccharide analogues (1-6) the first (inner) sugar in the carbohydrate chain is a 3-azido-2,3,6-trideoxy-L-lyxo-alpha-hexopyranose; the second (outer) sugars that are linked via alpha(1 -> 4) to the first sugar are a series of uncommon sugars. Their cytotoxicities were examined in drug-sensitive leukemia cells K562 and doxorubicin-resistant K562/Dox cells by MTS assay. In drug-sensitive cells, compounds 1-6 were found to be active against leukemia K562 cells with IC50 in the nanomolar range (200-1100 nM), while compounds 2-5 with 2,6-dideoxy sugars showed better activity than compounds 1 and 6 with 2,3,6-trideoxy sugars. In doxorubicin-resistant K562/Dox cells, compounds 1, 3, and 5 exhibited much better activities (with IC50 between 0.29 and 2.0 mu M) than DNR (with IC50 > 5 mu M). Compound 3 emerged as the most active compound, showing at least 17-fold higher activity against drug-resistant cells than parent compound DNR. The IC50 values of compound 3 in both drug-sensitive and drug-resistant cells are identical, which indicates that compound 3 completely overcomes drug resistance. Structure-activity relationship (SAR) studies showed that the substitution and orientation of the 3-OH group in the second sugar significantly influence its activity against drug-resistant leukemia. These results suggest that sugar modifications of anthracyclines change their activity and overcome drug resistance.