cyclohexyl (2S)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate | 1261254-02-7

• 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: cyclohexyl (2S)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-oxo-1H-purin-9-yl)-4-fluoro-3-hydroxy-4-methyloxolan-2-yl]methoxy-phenoxyphosphoryl]amino]propanoate
• CAS: 1261254-02-7
• 化学式: C₂₆H₃₄FN₆O₈P
• 分子量: 608.564
• InChiKey: FRVBHGLFIAIPBP-JUMSPBSPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  189
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  [(2R,3R,4R)-3-(benzoyloxy)-4-fluoro-5-hydroxy-4-methyltetrahydrofuran-2-yl]methylbenzoate 在 N-甲基咪唑 、 sodium methylate 、 三苯基膦 、 2-巯基乙醇 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 16.0h， 生成 cyclohexyl (2S)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-oxo-1H-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

文献信息

• Discovery of PSI-353661, a Novel Purine Nucleotide Prodrug for the Treatment of HCV Infection
  作者：Wonsuk Chang、Donghui Bao、Byoung-Kwon Chun、Devan Naduthambi、Dhanapalan Nagarathnam、Suguna Rachakonda、P. Ganapati Reddy、Bruce S. Ross、Hai-Ren Zhang、Shalini Bansal、Christine L. Espiritu、Meg Keilman、Angela M. Lam、Congrong Niu、Holly Micolochick Steuer、Phillip A. Furman、Michael J. Otto、Michael J. Sofia

  DOI：10.1021/ml100209f

  日期：2011.2.10

  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.