5'-O-[[[(1S)-2-butoxy-1-methyl-2-oxoethyl]amino][(4-chloro-1-naphthalenyl)oxy]phosphinyl]-2'-C-methylcytidine | 946511-46-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5'-O-[[[(1S)-2-butoxy-1-methyl-2-oxoethyl]amino][(4-chloro-1-naphthalenyl)oxy]phosphinyl]-2'-C-methylcytidine
• 英文别名: butyl (2S)-2-[[[(2R,3R,4R,5R)-5-(4-amino-2-oxo-pyrimidin-1-yl)-3,4-dihydroxy-4-methyl-tetrahydrofuran-2-yl]methoxy-[(4-chloro-1-naphthyl)oxy]phosphoryl]amino]propanoate；butyl (2S)-2-[[[(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-(4-chloronaphthalen-1-yl)oxyphosphoryl]amino]propanoate
• CAS: 946511-46-2
• 化学式: C₂₇H₃₄ClN₄O₉P
• 分子量: 625.015
• InChiKey: NHDIEQXJYYBIDY-RTZRXASASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  42
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  182
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  、 2'-C-甲基胞嘧啶核苷 在 叔丁基氯化镁 作用下， 以 四氢呋喃 为溶剂， 生成 5'-O-[[[(1S)-2-butoxy-1-methyl-2-oxoethyl]amino][(4-chloro-1-naphthalenyl)oxy]phosphinyl]-2'-C-methylcytidine
  参考文献：
  名称：

  Phosphoramidate Prodrugs of 2′-C-Methylcytidine for Therapy of Hepatitis C Virus Infection

  摘要：

  The application of a phosphoramidate prodrug approach to 2'-C-methylcytidine (NM107), the first nucleoside inhibitor of the hepatitis C virus (HCV) NS5B polymerase, is reported. 2'-C-Methylcytidine, as its valyl ester prodrug (NM283), was efficacious in reducing the viral load in patients infected with HCV. Several of the phosphoramidates prepared demonstrated a 10- to 200-fold superior potency with respect to the parent nucleoside in the cell-based replicon assay. This is due to higher levels of 2'-C-methylcytidine triphosphate in the cells. These prodrugs are efficiently activated and converted to the triphosphate in hepatocytes of several species. Our SAR studies ultimately led to compounds that gave high levels of NTP in hamster and rat liver after subcutaneous dosing and that were devoid of the toxic phenol moiety usually found in ProTides.

  DOI：

  10.1021/jm900447q