4-phenylethynyl-1-β-D-ribofuranosylpyrazole-3-carboxamide | 1002761-64-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 吡唑核糖核苷和核糖核苷酸
• 英文名称: 4-phenylethynyl-1-β-D-ribofuranosylpyrazole-3-carboxamide
• 英文别名: 1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-4-(2-phenylethynyl)pyrazole-3-carboxamide
• CAS: 1002761-64-9
• 化学式: C₁₇H₁₇N₃O₅
• 分子量: 343.339
• InChiKey: IXSVQAIOCGFUJM-DNNBLBMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  131
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-phenylethynyl-1-β-D-ribofuranosylpyrazole-3-carboxamide 在 Proton Sponge 、 三氯氧磷 、 三正丁胺 、 三丁基焦磷酸铵 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以7%的产率得到4-phenylethynyl-1-β-D-ribofuranosylpyrazole-3-carboxamide 5'-triphosphate
  参考文献：
  名称：

  Effects of Introduction of Hydrophobic Group on Ribavirin Base on Mutation Induction and Anti-RNA Viral Activity

  摘要：

  One of the possible mechanisms of antiviral action of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide, 1) is the accumulation of mutations in viral genomic RNA. The ambiguous incorporation of 5'-triphosphate of ribavirin (RTP, 8) by a viral RNA-dependent RNA polymerase (RdRp) is a key step of the mutation induction. We synthesized three ribavirin analogues that possess hydrophobic groups, 4-iodo-1- 1-beta-D-ribofuranosylpyrazole-3-carboxamide (7a), 4-propynyl-1-beta-D-ribofuranosylpyrazole-3-carboxamide (7b), and 4-phenylethynyl-1-beta-D-ribofuranosylpyrazole-3-carboxamide (7c), and the corresponding triphosphates (9a, 9b, and 9c, respectively). Steady-state kinetics analysis of the incorporation of these triphosphate analogues by a poliovirus RdRp, 3D(pol), revealed that while the incorporation efficiency of 9a was comparable to RTP, 9b and 9c showed lower efficiency than RTP. Antipolioviral activity of 7a and 7b was much more moderate than ribavirin, and 7c showed no antipolioviral activity. Effects of substituting groups on the incorporation efficiency by 3D(pol) and a strategy for a rational design of more active ribavirin analogues are discussed.

  DOI：

  10.1021/jm7009952
• 作为产物：
  描述：

  methyl 4-phenylethynyl-1-(2',3',5'-tribenzoyl-β-D-ribofuranosyl)pyrazole-3-carboxylate 在 氨 作用下， 以 甲醇 为溶剂， 以74%的产率得到4-phenylethynyl-1-β-D-ribofuranosylpyrazole-3-carboxamide
  参考文献：
  名称：

  Effects of Introduction of Hydrophobic Group on Ribavirin Base on Mutation Induction and Anti-RNA Viral Activity

  摘要：

  One of the possible mechanisms of antiviral action of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide, 1) is the accumulation of mutations in viral genomic RNA. The ambiguous incorporation of 5'-triphosphate of ribavirin (RTP, 8) by a viral RNA-dependent RNA polymerase (RdRp) is a key step of the mutation induction. We synthesized three ribavirin analogues that possess hydrophobic groups, 4-iodo-1- 1-beta-D-ribofuranosylpyrazole-3-carboxamide (7a), 4-propynyl-1-beta-D-ribofuranosylpyrazole-3-carboxamide (7b), and 4-phenylethynyl-1-beta-D-ribofuranosylpyrazole-3-carboxamide (7c), and the corresponding triphosphates (9a, 9b, and 9c, respectively). Steady-state kinetics analysis of the incorporation of these triphosphate analogues by a poliovirus RdRp, 3D(pol), revealed that while the incorporation efficiency of 9a was comparable to RTP, 9b and 9c showed lower efficiency than RTP. Antipolioviral activity of 7a and 7b was much more moderate than ribavirin, and 7c showed no antipolioviral activity. Effects of substituting groups on the incorporation efficiency by 3D(pol) and a strategy for a rational design of more active ribavirin analogues are discussed.

  DOI：

  10.1021/jm7009952

文献信息

• Effects of Introduction of Hydrophobic Group on Ribavirin Base on Mutation Induction and Anti-RNA Viral Activity
  作者：Kei Moriyama、Tetsuya Suzuki、Kazuo Negishi、Jason D. Graci、Corinne N. Thompson、Craig E. Cameron、Masahiko Watanabe

  DOI：10.1021/jm7009952

  日期：2008.1.1

  One of the possible mechanisms of antiviral action of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide, 1) is the accumulation of mutations in viral genomic RNA. The ambiguous incorporation of 5'-triphosphate of ribavirin (RTP, 8) by a viral RNA-dependent RNA polymerase (RdRp) is a key step of the mutation induction. We synthesized three ribavirin analogues that possess hydrophobic groups, 4-iodo-1- 1-beta-D-ribofuranosylpyrazole-3-carboxamide (7a), 4-propynyl-1-beta-D-ribofuranosylpyrazole-3-carboxamide (7b), and 4-phenylethynyl-1-beta-D-ribofuranosylpyrazole-3-carboxamide (7c), and the corresponding triphosphates (9a, 9b, and 9c, respectively). Steady-state kinetics analysis of the incorporation of these triphosphate analogues by a poliovirus RdRp, 3D(pol), revealed that while the incorporation efficiency of 9a was comparable to RTP, 9b and 9c showed lower efficiency than RTP. Antipolioviral activity of 7a and 7b was much more moderate than ribavirin, and 7c showed no antipolioviral activity. Effects of substituting groups on the incorporation efficiency by 3D(pol) and a strategy for a rational design of more active ribavirin analogues are discussed.