(2R,3R,4R,5R)-5-[2-amino-6-(cyclopropylamino)purin-9-yl]-4-fluoro-2-(hydroxymethyl)-4-methyloxolan-3-ol | 1261254-43-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: (2R,3R,4R,5R)-5-[2-amino-6-(cyclopropylamino)purin-9-yl]-4-fluoro-2-(hydroxymethyl)-4-methyloxolan-3-ol
• CAS: 1261254-43-6
• 化学式: C₁₄H₁₉FN₆O₃
• 分子量: 338.342
• InChiKey: SWYUFOUFNUCCPR-AMJCQUEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  131
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-(氯苯氧基氧化膦基)-L-丙氨酸异丙酯 、 (2R,3R,4R,5R)-5-[2-amino-6-(cyclopropylamino)purin-9-yl]-4-fluoro-2-(hydroxymethyl)-4-methyloxolan-3-ol 在 N-甲基咪唑 作用下， 以 四氢呋喃 为溶剂， 生成 propan-2-yl (2S)-2-[[[(2R,3R,4R,5R)-5-[2-amino-6-(cyclopropylamino)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
• 作为产物：
  描述：

  [(2R,3R,4R)-3-(benzoyloxy)-4-fluoro-5-hydroxy-4-methyltetrahydrofuran-2-yl]methylbenzoate 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 (2R,3R,4R,5R)-5-[2-amino-6-(cyclopropylamino)purin-9-yl]-4-fluoro-2-(hydroxymethyl)-4-methyloxolan-3-ol
  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

文献信息

• Beta-D-2'-DEOXY-2'-alpha-FLUORO-2'-beta-C-SUBSTITUTED-2-MODIFIED-N6-SUBSTITUTED PURINE NUCLEOTIDES FOR HCV TREATMENT
  申请人：Atea Pharmaceuticals, Inc.

  公开号：US20160257706A1

  公开（公告）日：2016-09-08

  A compound of the structure: or a pharmaceutically acceptable salt or composition thereof for the treatment of a host infected with or exposed to an HCV virus or other disorders more fully described herein.

  一种结构的化合物： 或其药用可接受的盐或组合物，用于治疗感染或暴露于HCV病毒或其他在本文中更详细描述的疾病的宿主。