3'-O-[N-(tert-butoxycarbonyl)-L-valinyl]-2'-C-methyl-β-D-cytidine | 640725-70-8

• 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: 3'-O-[N-(tert-butoxycarbonyl)-L-valinyl]-2'-C-methyl-β-D-cytidine
• 英文别名: 2-tert-Butoxycarbonylamino-3-methyl-butyric acid 5-(4-amino-2-oxo-2H-pyrimidin-1-yl)-4-hydroxy-2-hydroxymethyl-4-methyltetrahydrofuran-3-yl ester；[(2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-4-hydroxy-2-(hydroxymethyl)-4-methyloxolan-3-yl] (2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoate
• CAS: 640725-70-8
• 化学式: C₂₀H₃₂N₄O₈
• 分子量: 456.496
• InChiKey: BPTJLSYQRQIELX-MEQGQZKHSA-N

物化性质

• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  173
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3'-O-[N-(tert-butoxycarbonyl)-L-valinyl]-2'-C-methyl-β-D-cytidine 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 以81%的产率得到3'-O-(L-valinyl)-2'-C-methyl-β-D-cytidine dihydrochloride
  参考文献：
  名称：

  Synthesis and Pharmacokinetics of Valopicitabine (NM283), an Efficient Prodrug of the Potent Anti-HCV Agent 2‘-C-Methylcytidine

  摘要：

  In our search for new therapeutic agents against chronic hepatitis C, a ribonucleoside analogue, 2'-C-methylcytidine, was discovered to be a potent and selective inhibitor in cell culture of a number of RNA viruses, including the pestivirus bovine viral diarrhea virus, a surrogate model for hepatitis C virus (HCV), and three flaviviruses, namely, yellow fever virus, West Nile virus, and dengue-2 virus. However, pharmacokinetic studies revealed that 2'-C-methylcytidine suffers from a low oral bioavailability. To overcome this limitation, we have synthesized the 3'-O-L-valinyl ester derivative (dihydrochloride form, valopicitabine, NM283) of 2'-C-methylcytidine. We detail herein for the first time the chemical synthesis and physicochemical characteristics of this anti-HCV prodrug candidate, as well as a comparative study of its pharmacokinetic parameters with those of its parent nucleoside analogue, 2'-C-methylcytidine.

  DOI：

  10.1021/jm0603623
• 作为产物：
  描述：

  2′,3′,5′-tri-O-benzoyl-2′-C-methyluridine 在 甲醇 、 4-二甲氨基吡啶 、 sodium methylate 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 3'-O-[N-(tert-butoxycarbonyl)-L-valinyl]-2'-C-methyl-β-D-cytidine
  参考文献：
  名称：

  NM 283, AN EFFICIENT PRODRUG OF THE POTENT ANTI-HCV AGENT 2′-C-METHYLCYTIDINE

  摘要：

  In order to improve the oral bioavailability of 2'-C-methylcytidine, a potent anti-HCV agent, the corresponding 3'-O-L-valinyl ester derivative (NM 283) has been synthesized. Based on its ease Of synthesis and its physicochemical properties, NM 283 has emerged as a promising antiviral drug for treatment of chronic HCV infection.

  DOI：

  10.1081/ncn-200060112

文献信息

• [EN] PROCESS FOR THE PRODUCTION OF 3'-NUCLEOSIDE PRODRUGS<br/>[FR] PROCEDE DE PRODUCTION DE PROMEDICAMENTS A BASE DE 3'-NUCLEOSIDES
  申请人：IDENIX CAYMAN LTD

  公开号：WO2004058792A1

  公开（公告）日：2004-07-15

  Provided is a single-step process for the selective 3'-acylation of a ribofuranosyl 2' or 3'-branched nucleoside. These compounds are useful as antiviral agents, and in particular,can be used to treat Flaviviridae infections in a host in need t hereof.

  提供了一种用于选择性对核糖呋喃糖苷2'或3'-支链核苷的3'-酰化的单步过程。这些化合物可用作抗病毒药物，特别是可以用于治疗宿主中的黄病毒科感染。
• NM 283, AN EFFICIENT PRODRUG OF THE POTENT ANTI-HCV AGENT 2′-<i>C</i>-METHYLCYTIDINE
  作者：C. Pierra、S. Benzaria、A. Amador、A. Moussa、S. Mathieu、R. Storer、G. Gosselin

  DOI：10.1081/ncn-200060112

  日期：2005.4.1

  In order to improve the oral bioavailability of 2'-C-methylcytidine, a potent anti-HCV agent, the corresponding 3'-O-L-valinyl ester derivative (NM 283) has been synthesized. Based on its ease Of synthesis and its physicochemical properties, NM 283 has emerged as a promising antiviral drug for treatment of chronic HCV infection.
• Synthesis and Pharmacokinetics of Valopicitabine (NM283), an Efficient Prodrug of the Potent Anti-HCV Agent 2‘-<i>C</i>-Methylcytidine
  作者：Claire Pierra、Agnès Amador、Samira Benzaria、Erika Cretton-Scott、Marc D'Amours、John Mao、Steven Mathieu、Adel Moussa、Edward G. Bridges、David N. Standring、Jean-Pierre Sommadossi、Richard Storer、Gilles Gosselin

  DOI：10.1021/jm0603623

  日期：2006.11.1

  In our search for new therapeutic agents against chronic hepatitis C, a ribonucleoside analogue, 2'-C-methylcytidine, was discovered to be a potent and selective inhibitor in cell culture of a number of RNA viruses, including the pestivirus bovine viral diarrhea virus, a surrogate model for hepatitis C virus (HCV), and three flaviviruses, namely, yellow fever virus, West Nile virus, and dengue-2 virus. However, pharmacokinetic studies revealed that 2'-C-methylcytidine suffers from a low oral bioavailability. To overcome this limitation, we have synthesized the 3'-O-L-valinyl ester derivative (dihydrochloride form, valopicitabine, NM283) of 2'-C-methylcytidine. We detail herein for the first time the chemical synthesis and physicochemical characteristics of this anti-HCV prodrug candidate, as well as a comparative study of its pharmacokinetic parameters with those of its parent nucleoside analogue, 2'-C-methylcytidine.