1-(4'-azido-4-N-benzoyl-2'-dideoxy-2',2'-difluoro-5'-iodo-β-D-ribofuranosyl)cytosine | 1145869-49-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(4'-azido-4-N-benzoyl-2'-dideoxy-2',2'-difluoro-5'-iodo-β-D-ribofuranosyl)cytosine
• 英文别名: [(2S,3R,5R)-2-azido-5-(4-benzamido-2-oxopyrimidin-1-yl)-4,4-difluoro-2-(iodomethyl)oxolan-3-yl] 4-methoxybenzoate
• CAS: 1145869-49-3
• 化学式: C₂₄H₁₉F₂IN₆O₆
• 分子量: 652.353
• InChiKey: DQYXXYFBYHHKFH-MQSCRBSSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  sodium benzoate 、 1-(4'-azido-4-N-benzoyl-2'-dideoxy-2',2'-difluoro-5'-iodo-β-D-ribofuranosyl)cytosine 在 15-冠醚-5 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 185.0h， 以44%的产率得到1-[4'-azido-4-N-5'-O-dibenzoyl-3'-O-(4-methoxybenzoyl)-2'-dideoxy-2',2'-difluoro-β-D-ribofuranosyl]cytosine
  参考文献：
  名称：

  The Design, Synthesis, and Antiviral Activity of Monofluoro and Difluoro Analogues of 4′-Azidocytidine against Hepatitis C Virus Replication: The Discovery of 4′-Azido-2′-deoxy-2′-fluorocytidine and 4′-Azido-2′-dideoxy-2′,2′-difluorocytidine

  摘要：

  The discovery of 4'-azidocytidine (3) (R1479) (J. Biol. Chem. 2006, 281, 3793; Bioorg. Med. Chem. Lett. 2007, 17, 2570) as a potent inhibitor of RNA synthesis by NS5B (EC50 = 1.28 mu M), the RNA polymerase encoded by hepatitis C virus (HCV), has led to the synthesis and biological evaluation of several monofluoro and difluoro derivatives of 4'-azidocytidine. The most potent compounds in this series were 4'-azido-2'-deoxy-2',2'-difluorocytidine and 4'-azido-2'-deoxy-2'-fluoroarabinocytidine with antiviral EC50 of 66 nM and 24 nM in the HCV replicon system, respectively. The structure-activity relationships within this series were discussed. which led to the discovery of these novel nucleoside analogues with the most potent compound, showing more than a 50-fold increase in antiviral potency as compared to 4'-azidocytidine (3).

  DOI：

  10.1021/jm801595c
• 作为产物：
  描述：

  N-[1-[(2R,4R,5S)-5-azido-3,3-difluoro-4-hydroxy-5-(iodomethyl)oxolan-2-yl]-2-oxopyrimidin-4-yl]benzamide 、 对甲氧基苯甲酰氯 在 N-甲基吗啉 、 4-二甲氨基吡啶 、 N-乙酰基-D-半胱氨酸 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以3.33 g的产率得到1-(4'-azido-4-N-benzoyl-2'-dideoxy-2',2'-difluoro-5'-iodo-β-D-ribofuranosyl)cytosine
  参考文献：
  名称：

  The Design, Synthesis, and Antiviral Activity of Monofluoro and Difluoro Analogues of 4′-Azidocytidine against Hepatitis C Virus Replication: The Discovery of 4′-Azido-2′-deoxy-2′-fluorocytidine and 4′-Azido-2′-dideoxy-2′,2′-difluorocytidine

  摘要：

  The discovery of 4'-azidocytidine (3) (R1479) (J. Biol. Chem. 2006, 281, 3793; Bioorg. Med. Chem. Lett. 2007, 17, 2570) as a potent inhibitor of RNA synthesis by NS5B (EC50 = 1.28 mu M), the RNA polymerase encoded by hepatitis C virus (HCV), has led to the synthesis and biological evaluation of several monofluoro and difluoro derivatives of 4'-azidocytidine. The most potent compounds in this series were 4'-azido-2'-deoxy-2',2'-difluorocytidine and 4'-azido-2'-deoxy-2'-fluoroarabinocytidine with antiviral EC50 of 66 nM and 24 nM in the HCV replicon system, respectively. The structure-activity relationships within this series were discussed. which led to the discovery of these novel nucleoside analogues with the most potent compound, showing more than a 50-fold increase in antiviral potency as compared to 4'-azidocytidine (3).

  DOI：

  10.1021/jm801595c