1-<5'-deoxy-5'-(dimethylphosphono)-β-D-threo-pentofuranosyl>thymine | 172293-39-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 2 '，5'-二脱氧核苷
• 英文名称: 1-<5'-deoxy-5'-(dimethylphosphono)-β-D-threo-pentofuranosyl>thymine
• 英文别名: 1-[(2R,4R,5S)-5-(dimethoxyphosphorylmethyl)-4-hydroxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 172293-39-9
• 化学式: C₁₂H₁₉N₂O₇P
• 分子量: 334.266
• InChiKey: ZZFPKOVERLKCAY-OPRDCNLKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-<5'-deoxy-5'-(dimethylphosphono)-β-D-threo-pentofuranosyl>thymine 在 吡啶 、 1,3-二甲基-2-咪唑啉酮 、 2,3,5-三甲基吡啶 、 三氯甲基磺酰氯 、 4-二甲氨基吡啶 、 叠氮化锂 、 三甲基溴硅烷 作用下， 以 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 45.0h， 生成 (2R,4S,5R)-1-<4-azidotetrahydro-5-<<<3'-O-<5'-O-(tert-butyldimethylsilyl)thymidinyl>>phosphinico>methyl>-2-furyl>thymine
  参考文献：
  名称：

  Design, Synthesis, and Structure-Activity Relationship of Novel Dinucleotide Analogs as Agents against Herpes and Human Immunodeficiency Viruses

  摘要：

  A new acyclic nucleoside phosphonate (13) containing an adenine moiety was synthesized, which acted as an excellent inhibitor of calf mucosal adenosine deaminase. This inhibitory property allows it to exert great synergistic effect on certain antiviral agents (e.g., ara-A, 37). Phosphonate 13 was not phosphorylated by the bovine brain guanylate kinase nor by 5-phosphoribosyl 1-pyrophosphate synthetase. Syntheses of biologically active nucleotide phosphonate 40 and its phosphonoamidate derivative 42 were accomplished, which showed remarkable activity against herpes viruses and exhibited low host cell toxicity. 3'-Azido-nucleoside phosphonate 20 and 3'-fluoronucleoside phosphonate 32, as well as the corresponding dinucleotide analogs 47 and 48, and their respective phosphonoamidates 53-56 were also synthesized as new compounds, among which phosphonoamidates 53-56 showed potent activity against human immunodeficiency virus. Phosphonoamidates 55 and 56 bearing a methyl D-alaninate moiety exhibited less cellular toxicity than 53 and 54 bearing a methyl L-alaninate moiety. Nucleotide phosphonate 40 as well as dinucleotide phosphonates 47 and 48 were found susceptible to degradation by phosphodiesterases. Their respective phosphonoamidates 42 and 53-56, however, were completely resistant to snake venom and spleen enzymes.

  DOI：

  10.1021/jm00023a004
• 作为产物：
  描述：

  1-(5'-deoxy-5'-bromo-β-D-threo-pentofuranosyl)thymine 、 三甲氧基磷 反应 20.0h， 以40%的产率得到1-<5'-deoxy-5'-(dimethylphosphono)-β-D-threo-pentofuranosyl>thymine
  参考文献：
  名称：

  Design, Synthesis, and Structure-Activity Relationship of Novel Dinucleotide Analogs as Agents against Herpes and Human Immunodeficiency Viruses

  摘要：

  A new acyclic nucleoside phosphonate (13) containing an adenine moiety was synthesized, which acted as an excellent inhibitor of calf mucosal adenosine deaminase. This inhibitory property allows it to exert great synergistic effect on certain antiviral agents (e.g., ara-A, 37). Phosphonate 13 was not phosphorylated by the bovine brain guanylate kinase nor by 5-phosphoribosyl 1-pyrophosphate synthetase. Syntheses of biologically active nucleotide phosphonate 40 and its phosphonoamidate derivative 42 were accomplished, which showed remarkable activity against herpes viruses and exhibited low host cell toxicity. 3'-Azido-nucleoside phosphonate 20 and 3'-fluoronucleoside phosphonate 32, as well as the corresponding dinucleotide analogs 47 and 48, and their respective phosphonoamidates 53-56 were also synthesized as new compounds, among which phosphonoamidates 53-56 showed potent activity against human immunodeficiency virus. Phosphonoamidates 55 and 56 bearing a methyl D-alaninate moiety exhibited less cellular toxicity than 53 and 54 bearing a methyl L-alaninate moiety. Nucleotide phosphonate 40 as well as dinucleotide phosphonates 47 and 48 were found susceptible to degradation by phosphodiesterases. Their respective phosphonoamidates 42 and 53-56, however, were completely resistant to snake venom and spleen enzymes.

  DOI：

  10.1021/jm00023a004

文献信息

• Design, Synthesis, and Structure-Activity Relationship of Novel Dinucleotide Analogs as Agents against Herpes and Human Immunodeficiency Viruses
  作者：Gholam H. Hakimelahi、Ali A. Moosavi-Movahedi、Majid M. Sadeghi、Shwu-Chen Tsay、Jih Ru Hwu

  DOI：10.1021/jm00023a004

  日期：1995.11

  A new acyclic nucleoside phosphonate (13) containing an adenine moiety was synthesized, which acted as an excellent inhibitor of calf mucosal adenosine deaminase. This inhibitory property allows it to exert great synergistic effect on certain antiviral agents (e.g., ara-A, 37). Phosphonate 13 was not phosphorylated by the bovine brain guanylate kinase nor by 5-phosphoribosyl 1-pyrophosphate synthetase. Syntheses of biologically active nucleotide phosphonate 40 and its phosphonoamidate derivative 42 were accomplished, which showed remarkable activity against herpes viruses and exhibited low host cell toxicity. 3'-Azido-nucleoside phosphonate 20 and 3'-fluoronucleoside phosphonate 32, as well as the corresponding dinucleotide analogs 47 and 48, and their respective phosphonoamidates 53-56 were also synthesized as new compounds, among which phosphonoamidates 53-56 showed potent activity against human immunodeficiency virus. Phosphonoamidates 55 and 56 bearing a methyl D-alaninate moiety exhibited less cellular toxicity than 53 and 54 bearing a methyl L-alaninate moiety. Nucleotide phosphonate 40 as well as dinucleotide phosphonates 47 and 48 were found susceptible to degradation by phosphodiesterases. Their respective phosphonoamidates 42 and 53-56, however, were completely resistant to snake venom and spleen enzymes.