1-(((5S)-2-((3,6,9,12,15,18-hexaoxaicosyl)oxy)-2-oxido-1,4,2-dioxaphosphinan-5-yl)methyl)-4-aminopyrimidin-2(1H)-one | 1313816-33-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-(((5S)-2-((3,6,9,12,15,18-hexaoxaicosyl)oxy)-2-oxido-1,4,2-dioxaphosphinan-5-yl)methyl)-4-aminopyrimidin-2(1H)-one
• CAS: 1313816-33-9
• 化学式: C₂₂H₄₀N₃O₁₁P
• 分子量: 553.547
• InChiKey: AFIGBSXOEAVXKD-PTJRXNEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.53
• 重原子数：
  37.0
• 可旋转键数：
  22.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  161.05
• 氢给体数：
  1.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  1-(((5S)-2-((3,6,9,12,15,18-hexaoxaicosyl)oxy)-2-oxido-1,4,2-dioxaphosphinan-5-yl)methyl)-4-aminopyrimidin-2(1H)-one 在 氨 、 水 作用下， 以255 mg的产率得到(S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine 3,6,9,12,15,18-hexaoxaeicosyl ester
  参考文献：
  名称：

  New prodrugs of Adefovir and Cidofovir

  摘要：

  New Adefovir (PMEA) prodrugs with a pro-moiety consisting of decyl or decyloxyethyl chain bearing hydroxyl function(s), hexaethyleneglycol or a (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl unit were prepared starting from the tetrabutylammonium salt of the phosphonate drug and an appropriate alkyl bromide or tosylate. Analogously, two esters of Cidofovir [(S)-HPMPC] bearing a hexaethyleneglycol moiety were prepared. The activity of the prodrugs was evaluated in vitro against different virus families. A loss in the antiviral activities of the hydroxylated decyl or decyloxyethyl esters and hexaethyleneglycol esters of PMEA against human immunodeficiency virus (HIV) and herpesviruses [ including herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (CMV)] occurred in comparison with the parent compound. On the other hand, the (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl ester of PMEA showed significant activities against HIV and herpesviruses. (S)-HPMPC prodrugs exhibited anti-cytomegalovirus activities in the same range as the parent drug, whereas the anti-HSV and anti-VZV activities were one-to seven-fold lower than that of Cidofovir. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.04.016
• 作为产物：
  描述：

  六甘醇 在 四丁基氢氧化铵 、 4-甲基苯磺酸吡啶 、 sodium hydride 、 三乙胺 、 potassium iodide 、 silver(l) oxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 mineral oil 为溶剂， 反应 134.25h， 生成 1-(((5S)-2-((3,6,9,12,15,18-hexaoxaicosyl)oxy)-2-oxido-1,4,2-dioxaphosphinan-5-yl)methyl)-4-aminopyrimidin-2(1H)-one
  参考文献：
  名称：

  New prodrugs of Adefovir and Cidofovir

  摘要：

  New Adefovir (PMEA) prodrugs with a pro-moiety consisting of decyl or decyloxyethyl chain bearing hydroxyl function(s), hexaethyleneglycol or a (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl unit were prepared starting from the tetrabutylammonium salt of the phosphonate drug and an appropriate alkyl bromide or tosylate. Analogously, two esters of Cidofovir [(S)-HPMPC] bearing a hexaethyleneglycol moiety were prepared. The activity of the prodrugs was evaluated in vitro against different virus families. A loss in the antiviral activities of the hydroxylated decyl or decyloxyethyl esters and hexaethyleneglycol esters of PMEA against human immunodeficiency virus (HIV) and herpesviruses [ including herpes simplex virus (HSV), varicella-zoster virus (VZV), and human cytomegalovirus (CMV)] occurred in comparison with the parent compound. On the other hand, the (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl ester of PMEA showed significant activities against HIV and herpesviruses. (S)-HPMPC prodrugs exhibited anti-cytomegalovirus activities in the same range as the parent drug, whereas the anti-HSV and anti-VZV activities were one-to seven-fold lower than that of Cidofovir. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.04.016