9-[2-(5,6,7,8-tetrahydro-1-naphthyloxy(2,2-dimethylpropoxy-L-alaninyl)phosphonomethoxy)ethyl]adenine

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 9-[2-(5,6,7,8-tetrahydro-1-naphthyloxy(2,2-dimethylpropoxy-L-alaninyl)phosphonomethoxy)ethyl]adenine
• 英文别名: 2,2-dimethylpropyl (2S)-2-[[2-(6-aminopurin-9-yl)ethoxymethyl-tetralin-5-yloxy-phosphoryl]amino]propanoate；2,2-dimethylpropyl (2S)-2-[[2-(6-aminopurin-9-yl)ethoxymethyl-(5,6,7,8-tetrahydronaphthalen-1-yloxy)phosphoryl]amino]propanoate
• 化学式: C₂₆H₃₇N₆O₅P
• 分子量: 544.591
• InChiKey: SYRCYVSCXMSHNC-GXWMPHIDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  38
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  144
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  阿德福韦 在 吡啶 、 2,2'-二硫二吡啶 、 三乙胺 、 三苯基膦 作用下， 以 乙腈 为溶剂， 反应 21.0h， 生成 9-[2-(5,6,7,8-tetrahydro-1-naphthyloxy(2,2-dimethylpropoxy-L-alaninyl)phosphonomethoxy)ethyl]adenine
  参考文献：
  名称：

  PMPA and PMEA prodrugs for the treatment of HIV infections and human papillomavirus (HPV) associated neoplasia and cancer

  摘要：

  The synthesis and in vitro biological evaluation of novel phosphonamidate and phosphonodiamidate prodrugs of adefovir and tenofovir are reported. The selected synthetic approach from free phosphonic acid via bis-trimethylsilyl ester intermediates affords (L)-alanine ester derivatives in 10-70% yields. When assessed for their anti-HIV activity, all the prodrugs showed submicromolar activity. Noteworthy, the most potent derivative in the adefovir series contained a 5,6,7,8-tetrahydronaphtyl group, herein reported for the first time as an aryl moiety in a ProTide. A pronounced cytostatic activity of the above prodrugs is also reported. Selected compounds were tested for their antiproliferative activity against HPV-transformed cells and they were found significantly more active in comparison to their parent compounds. In this study a slightly improved activity of the adefovir derivatives over those of tenofovir was also noticed. However, no specificity for naturally HPV-transformed cell lines was observed. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.03.051

文献信息

• PMPA and PMEA prodrugs for the treatment of HIV infections and human papillomavirus (HPV) associated neoplasia and cancer
  作者：Fabrizio Pertusati、Karen Hinsinger、Áine Sinéad Flynn、Ned Powell、Amanda Tristram、Jan Balzarini、Christopher McGuigan

  DOI：10.1016/j.ejmech.2014.03.051

  日期：2014.5

  The synthesis and in vitro biological evaluation of novel phosphonamidate and phosphonodiamidate prodrugs of adefovir and tenofovir are reported. The selected synthetic approach from free phosphonic acid via bis-trimethylsilyl ester intermediates affords (L)-alanine ester derivatives in 10-70% yields. When assessed for their anti-HIV activity, all the prodrugs showed submicromolar activity. Noteworthy, the most potent derivative in the adefovir series contained a 5,6,7,8-tetrahydronaphtyl group, herein reported for the first time as an aryl moiety in a ProTide. A pronounced cytostatic activity of the above prodrugs is also reported. Selected compounds were tested for their antiproliferative activity against HPV-transformed cells and they were found significantly more active in comparison to their parent compounds. In this study a slightly improved activity of the adefovir derivatives over those of tenofovir was also noticed. However, no specificity for naturally HPV-transformed cell lines was observed. (C) 2014 Elsevier Masson SAS. All rights reserved.