7-(3-azido-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)daunorubicinone | 874384-80-2

• 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-(3-azido-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)daunorubicinone
• 英文别名: 3'-azido-3'-deamino daunorubicin；3'-azido-3'-deaminodaunorubicin；3'-azidodeaminodaunorubicin；3'-azidodaunorubicin；ADNR；3'-azido-deamino-daunorubicin；(7S,9S)-9-acetyl-7-[(2R,4S,5S,6S)-4-azido-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7H-tetracene-5,12-dione
• CAS: 874384-80-2
• 化学式: C₂₇H₂₇N₃O₁₀
• 分子量: 553.525
• InChiKey: RQILHTMNLJXCQG-VGBVRHCVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  40
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  174
• 氢给体数：
  4
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  7-(3-azido-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)daunorubicinone 在 palladium diacetate 4-二甲氨基吡啶 、 1,1'-bis(diphenylphosphino)ferrocene 、 甲酸:三乙胺 1:1 、 N,N-二异丙基乙胺 、 三苯基膦 、 potassium iodide 、 magnesium chloride 作用下， 以 四氢呋喃 、 吡啶 、 N,N-二甲基甲酰胺 为溶剂， 反应 10.5h， 生成 盐酸依达比星
  参考文献：
  名称：

  METHOD OF PRODUCING 4-DEMETHOXYDAUNORUBICIN

  摘要：

  本发明涉及一种合成4-去甲氧基多柔红霉素（伊达霉素）的方法，其化学结构如式（I），该方法涉及在软性Lewis酸存在下对3'-Prot-多柔红霉素进行去甲基化。本发明的方法不包括在碳C7处断裂糖苷键，因此导致合成周期更快，最终产物的产率提高。

  公开号：

  US20120277415A1
• 作为产物：
  描述：

  柔红霉素 盐酸盐 生成 7-(3-azido-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)daunorubicinone
  参考文献：
  名称：

  METHOD OF ARALKYLATION OF 4'-HYDROXYL GROUP OF ANTHRACYLINS

  摘要：

  本发明提供了一种利用芳基烷基化试剂R3-CH2X（例如BnBr）根据图1所示的反应途径进行蒽环素的芳基烷基化的方法。本发明认识到4-R1，3'-N3-多柔比星是适合选择性4'-O-苄基化的底物，产生4-R1，3'-N3-4'-O-芳基烷基-多柔比星（特别是4'-O-Bn-多柔比星）。因此，本发明提供了一种简单生产蒽环素4'-O-芳基烷基化衍生物的途径，可有效用于生产蒽环素。

  公开号：

  US20090176974A1

文献信息

• Spectroscopic, Viscositic and Molecular Modeling Studies on the Interaction of 3′-Azido-Daunorubicin Thiosemicarbazone with DNA
  作者：Fengling Cui、Qingfeng Liu、Hongxia Luo、Guisheng Zhang

  DOI：10.1007/s10895-013-1285-8

  日期：2014.1

  A new daunorubicin has been synthesized and structurally characterized. The interaction of native calf thymus DNA (ctDNA) with 3′-azido-daunorubicin thiosemicarbazone (ADNRT) was investigated under simulated physiological conditions by multi-spectroscopic techniques, viscometric measurements and molecular modeling study. It concluded that ADNRT could intercalate into the base pairs of ctDNA, and the fluorescence quenching by ctDNA was static quenching type. Thermodynamic parameters calculated suggested that the binding of ADNRT to ctDNA was mainly driven by hydrophobic interactions. The relative viscosity of ctDNA increased with the addition of ADNRT, which confirmed the intercalation mode. Furthermore, molecular modeling studies corroborate the above experimental results.

  我们合成了一种新的daunorubicin，并确定了其结构特征。在模拟生理条件下，通过多光谱技术、粘度测量和分子建模研究了原生小牛胸腺 DNA（ctDNA）与 3′-叠氮-daunorubicin thiosemicarbazone（ADNRT）的相互作用。结果表明，ADNRT 能插入到 ctDNA 的碱基对中，ctDNA 对其产生的荧光淬灭为静态淬灭。计算得出的热力学参数表明，ADNRT与ctDNA的结合主要由疏水相互作用驱动。ctDNA的相对粘度随着ADNRT的加入而增加，这证实了插层模式。此外，分子建模研究也证实了上述实验结果。
• 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.
• WO2006/124720
  申请人：——

  公开号：——

  公开（公告）日：——
• Syntheses and biological activity of bisdaunorubicins
  作者：Guisheng Zhang、Lanyan Fang、Lizhi Zhu、Duxin Sun、Peng George Wang

  DOI：10.1016/j.bmc.2005.08.014

  日期：2006.1

  To study the length and flexibility of the linkers between two monomers of bisdaunorubicins for their activity against cancer cells, seven bisdaunorubicins were rationally designed and synthesized through click chemistry. Their cytotoxicity was tested in leukemia cells with MTS assay. The results showed that the compounds with short linkers exhibited higher activity than the compounds with long linkers, while the flexibility of the linker also contributed to their activity. These results indicated that the length and flexibility of the linkers between two monomers in bisdaunorubicins are very critical to maintain their activity against cancer cells. (c) 2005 Elsevier Ltd. All rights reserved.
• Method of producing 4-demethoxydaunorubicin
  申请人：Synbias Pharma AG

  公开号：EP2518077B1

  公开（公告）日：2016-01-06