9-[2-(phosphonomethoxy)ethyl]adenine bis(3,6,9,12,15,18-hexaoxaeicosyl) ester | 1313815-78-9

• 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: 9-[2-(phosphonomethoxy)ethyl]adenine bis(3,6,9,12,15,18-hexaoxaeicosyl) ester
• 英文别名: 9-[2-[Bis[2-[2-[2-[2-[2-(2-ethoxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]phosphorylmethoxy]ethyl]purin-6-amine
• CAS: 1313815-78-9
• 化学式: C₃₆H₆₈N₅O₁₆P
• 分子量: 857.934
• InChiKey: CINZVYWNLVZDLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2
• 重原子数：
  58
• 可旋转键数：
  45
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  225
• 氢给体数：
  1
• 氢受体数：
  20

反应信息

• 作为反应物：
  描述：

  9-[2-(phosphonomethoxy)ethyl]adenine bis(3,6,9,12,15,18-hexaoxaeicosyl) ester 在 叠氮化锂 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以80%的产率得到9-[2-(phosphonomethoxy)ethyl]adenine 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 126.25h， 生成 9-[2-(phosphonomethoxy)ethyl]adenine bis(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

文献信息

• New prodrugs of Adefovir and Cidofovir
  作者：Tomáš Tichý、Graciela Andrei、Martin Dračínský、Antonín Holý、Jan Balzarini、Robert Snoeck、Marcela Krečmerová

  DOI：10.1016/j.bmc.2011.04.016

  日期：2011.6

  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.