diethyl <2-<(6-methoxypurin-9-yl)methoxy>ethyl>phosphonate | 172293-37-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: diethyl <2-<(6-methoxypurin-9-yl)methoxy>ethyl>phosphonate
• 英文别名: Diethyl [2-[(6-Methoxypurin-9-yl)methoxy]ethyl]phosphonate；9-(2-diethoxyphosphorylethoxymethyl)-6-methoxypurine
• CAS: 172293-37-7
• 化学式: C₁₃H₂₁N₄O₅P
• 分子量: 344.307
• InChiKey: HPGCCSLTZKEMSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  23
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  97.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  diethyl <2-<(6-methoxypurin-9-yl)methoxy>ethyl>phosphonate 在 吡啶 、 2,3,5-三甲基吡啶 、 三氯甲基磺酰氯 、 2,4,6-三异丙基苯磺酰氯 、 三甲基溴硅烷 、 四丁基氟化铵 、 氨 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 63.5h， 生成 9-(β-D-arabinofuranosyl)adenine-3'-<(methoxyalaninyl)<2-(adenin-9-ylmethoxy)ethyl>phosphonate>
  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：

  9-(2-Bromo-ethoxymethyl)-6-methoxy-9H-purine 、 亚磷酸三乙酯 反应 24.0h， 以30%的产率得到diethyl <2-<(6-methoxypurin-9-yl)methoxy>ethyl>phosphonate
  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

• Adenylate analogs as potent anti-herpes virus agents
  申请人：National Science Council

  公开号：US05733890A1

  公开（公告）日：1998-03-31

  Novel adenylate analogs having the following formula are synthesized in the present invention, which are found active against herpes simplex viruses: ##STR1## wherein R.sup.1 is hydroxyl, C.sub.1 -C.sub.4 alkoxy, an amino ester radical of --NHR.sup.3 COOR.sup.4, wherein R.sup.3 is a bivalent C.sub.1 -C.sub.4 saturated hydrocarbon and R.sup.4 is C.sub.1 -C.sub.4 alkyl; and R.sup.2 is hydroxyl, --O.sup.+ NH.sub.4 or ##STR2##

  本发明合成了具有以下公式的新型腺苷酸类似物，发现对单纯疱疹病毒具有活性： ##STR1## 其中，R.sup.1是羟基、C.sub.1-C.sub.4烷氧基、--NHR.sup.3 COOR.sup.4的氨基酯基团，其中R.sup.3是双价的C.sub.1-C.sub.4饱和碳氢化合物，R.sup.4是C.sub.1-C.sub.4烷基；而R.sup.2是羟基、--O.sup.+ NH.sub.4或##STR2##。
• 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.