2',2'-difluoro-2'-deoxycytidine-5'-O-[N-(benzoyl)]thiophosphoramidate

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 2',2'-difluoro-2'-deoxycytidine-5'-O-[N-(benzoyl)]thiophosphoramidate
• 英文别名: N-[[(2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-4,4-difluoro-3-hydroxyoxolan-2-yl]methoxy-hydroxy-sulfidophosphaniumyl]benzenecarboximidate
• 化学式: C₁₆H₁₆F₂N₄O₆PS
• 分子量: 461.363
• InChiKey: AVPHEYKTDVWNRI-UMJIFANGSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  154
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2',2'-difluoro-2'-deoxycytidine-5'-O-[N-(benzoyl)]thiophosphoramidate 在 戴斯-马丁氧化剂 作用下， 以 水 为溶剂， 以52%的产率得到2',2'-difluoro-2'-deoxycytidine-5'-O-[N-(benzoyl)]phosphoramidate
  参考文献：
  名称：

  N-Acyl-phosphoramidates as potential novel form of gemcitabine prodrugs

  摘要：

  Gemcitabine (dFdC) is a cytidine analog remarkably active against a wide range of solid tumors. Inside a cell, gemcitabine is phosphorylated by deoxycytidine kinase to yield gemcitabine monophosphate, further converted to gemcitabine di- and triphosphate. The most frequent form of acquired resistance to gemcitabine in vitro is the deoxycytidine kinase deficiency. Thus, proper prodrugs carrying the 5'-pdFdC moiety may help to overcome this problem. A series of new derivatives of gemcitabine possessing N-acyl(thio) phosphoramidate moieties were prepared and their cytotoxic properties were determined. N-Acyl-phosphoramidate derivatives of gemcitabine have similar cytotoxicity as gemcitabine itself, and have been found accessible to the cellular enzymes. The nicotinic carboxamide derivative of gemcitabine 5'-O-phosphorothioate occurred to be the best inhibitor of bacterial DNA polymerase I and human DNA polymerase alpha. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.02.034
• 作为产物：
  描述：

  苯甲酰胺 在 吡啶 、 sulfur 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 反应 51.0h， 生成 2',2'-difluoro-2'-deoxycytidine-5'-O-[N-(benzoyl)]thiophosphoramidate
  参考文献：
  名称：

  N-Acyl-phosphoramidates as potential novel form of gemcitabine prodrugs

  摘要：

  Gemcitabine (dFdC) is a cytidine analog remarkably active against a wide range of solid tumors. Inside a cell, gemcitabine is phosphorylated by deoxycytidine kinase to yield gemcitabine monophosphate, further converted to gemcitabine di- and triphosphate. The most frequent form of acquired resistance to gemcitabine in vitro is the deoxycytidine kinase deficiency. Thus, proper prodrugs carrying the 5'-pdFdC moiety may help to overcome this problem. A series of new derivatives of gemcitabine possessing N-acyl(thio) phosphoramidate moieties were prepared and their cytotoxic properties were determined. N-Acyl-phosphoramidate derivatives of gemcitabine have similar cytotoxicity as gemcitabine itself, and have been found accessible to the cellular enzymes. The nicotinic carboxamide derivative of gemcitabine 5'-O-phosphorothioate occurred to be the best inhibitor of bacterial DNA polymerase I and human DNA polymerase alpha. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.02.034

文献信息

• N-Acyl-phosphoramidates as potential novel form of gemcitabine prodrugs
  作者：Janina Baraniak、Aleksandra Pietkiewicz、Renata Kaczmarek、Ewa Radzikowska、Katarzyna Kulik、Karolina Krolewska、Marcin Cieslak、Agnieszka Krakowiak、Barbara Nawrot

  DOI：10.1016/j.bmc.2014.02.034

  日期：2014.4

  Gemcitabine (dFdC) is a cytidine analog remarkably active against a wide range of solid tumors. Inside a cell, gemcitabine is phosphorylated by deoxycytidine kinase to yield gemcitabine monophosphate, further converted to gemcitabine di- and triphosphate. The most frequent form of acquired resistance to gemcitabine in vitro is the deoxycytidine kinase deficiency. Thus, proper prodrugs carrying the 5'-pdFdC moiety may help to overcome this problem. A series of new derivatives of gemcitabine possessing N-acyl(thio) phosphoramidate moieties were prepared and their cytotoxic properties were determined. N-Acyl-phosphoramidate derivatives of gemcitabine have similar cytotoxicity as gemcitabine itself, and have been found accessible to the cellular enzymes. The nicotinic carboxamide derivative of gemcitabine 5'-O-phosphorothioate occurred to be the best inhibitor of bacterial DNA polymerase I and human DNA polymerase alpha. (C) 2014 Elsevier Ltd. All rights reserved.