| 1261254-35-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• CAS: 1261254-35-6
• 化学式: C₁₃H₁₇F₂N₅O₄
• 分子量: 345.306
• InChiKey: IMMBLHNUFBMCNQ-VHQAPHLWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.26
• 重原子数：
  24.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  128.54
• 氢给体数：
  3.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  、 (2S)-2-((氯(苯氧基)膦)氨基)丙酸乙酯 在 N-甲基咪唑 作用下， 以 四氢呋喃 为溶剂， 生成 ethyl (2S)-2-[[[(2R,3R,4R,5R)-5-[2-amino-6-(2-fluoroethoxy)purin-9-yl]-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
  参考文献：
  名称：

  Discovery of PSI-353661, a Novel Purine Nucleotide Prodrug for the Treatment of HCV Infection

  摘要：

  Hepatitis C virus afflicts approximately 180 million people worldwide, and the development of direct acting antivirals may offer substantial benefit compared to the current standard of care. Accordingly, prodrugs of 2'-deoxy-2'-fluoro-2'-C-methylguanosine monophosphate analogues were prepared and evaluated for their anti-HCV efficacy and tolerability. These prodrugs demonstrated >1000 fold greater potency than the parent nucleoside in a cell based replicon assay as a result of higher intracellular triphosphate levels. Further optimization led to the discovery of the clinical candidate PSI-353661, which has demonstrated strong in vitro, inhibition against HCV without cytotoxicity and equipotent activity against both the wild type and the known S282T nucleoside/tide resistant replicon. PSI-353661 is currently in preclinical development for the treatment of HCV.

  DOI：

  10.1021/ml100209f