(2S)isopropyl 2-((((2R,3R,4R,5R) 5-(2-amino-6-methoxy-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propanoate | 1231747-10-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S)isopropyl 2-((((2R,3R,4R,5R) 5-(2-amino-6-methoxy-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propanoate
• 英文别名: (2S)-isopropyl 2-(((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate；propan-2-yl (2S)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-methoxypurin-9-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
• CAS: 1231747-10-6
• 化学式: C₂₄H₃₂FN₆O₈P
• 分子量: 582.526
• InChiKey: KVCZQFHLXRMEIB-HEOQURLSSA-N

物化性质

• 沸点：
  759.7±70.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  40
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  182
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (2S)isopropyl 2-((((2R,3R,4R,5R) 5-(2-amino-6-methoxy-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propanoate 在 N-溴代丁二酰亚胺(NBS) 、 超重氢 、 palladium 10% on activated carbon 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 6.0h， 生成 isopropyl ((((2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl-8-t)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate
  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：

  N-(氯苯氧基氧化膦基)-L-丙氨酸异丙酯 、 (2R,3R,4R,5R)-5-(2-amino-6-methoxy-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)-4-methyltetrahydrofuran-3-ol 在 N-甲基咪唑 作用下， 以 四氢呋喃 为溶剂， 生成 (2S)isopropyl 2-((((2R,3R,4R,5R) 5-(2-amino-6-methoxy-9H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)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

文献信息

• [EN] PURINE NUCLEOSIDE PHOSPHORAMIDATE<br/>[FR] PHOSPHORAMIDATE DE NUCLÉOSIDE DE TYPE PURINE
  申请人：PHARMASSET INC

  公开号：WO2011123672A1

  公开（公告）日：2011-10-06

  Disclosed herein is a compound represented by formula 1 or its hydrate thereof in crystalline or crystal-like form.

  本文披露了一种由公式1表示的化合物或其水合物，以结晶或类晶体形式存在的化合物。
• NUCLEOSIDE ANALOGS
  申请人：BAO DONGHUI

  公开号：US20100286083A1

  公开（公告）日：2010-11-11

  A purified compound having activity against hepatitis C virus is disclosed.

  本发明揭示了一种对丙型肝炎病毒具有活性的纯化化合物。
• STEREOSELECTIVE SYNTHESIS OF PHOSPHORUS CONTAINING ACTIVES
  申请人：ROSS BRUCE S.

  公开号：US20110245484A1

  公开（公告）日：2011-10-06

  Disclosed herein are phosphorus-containing actives, their use as actives for treating diseases, and a stereoselective process for preparing the same. Also disclosed herein are useful synthetic intermediates and processes for preparing the same.

  本文披露了含磷活性物质，其作为治疗疾病的活性物质的用途，以及用于制备它们的立体选择性过程。本文还披露了有用的合成中间体和制备它们的过程。
• PURINE NUCLEOSIDE PHOSPHORAMIDATE
  申请人：CHANG WONSUK

  公开号：US20110257121A1

  公开（公告）日：2011-10-20

  Disclosed herein is a compound represented by formula 1 or its hydrate thereof in crystalline or crystal-like form.

  本文揭示了一种由公式1所表示的化合物或其水合物的晶体或类晶体形式。
• Purine nucleoside phosphoramidate
  申请人：Chang Wonsuk

  公开号：US08563530B2

  公开（公告）日：2013-10-22

  Disclosed herein is a compound represented by formula 1 or its hydrate thereof in crystalline or crystal-like form.

  本文披露了一种由公式1表示的化合物或其水合物，其以结晶或类晶体形式存在。