N-(5-{[(5S)-2-(2-(hexadecyloxy)ethoxy)-2-oxido-1,4,2-dioxaphosphinan-5-yl]methyl}-4-oxo-4,5-dihydro-1,3,5-triazin-2-yl)docosanamide | 1608457-45-9

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: N-(5-{[(5S)-2-(2-(hexadecyloxy)ethoxy)-2-oxido-1,4,2-dioxaphosphinan-5-yl]methyl}-4-oxo-4,5-dihydro-1,3,5-triazin-2-yl)docosanamide
• CAS: 1608457-45-9
• 化学式: C₄₇H₈₉N₄O₇P
• 分子量: 853.22
• InChiKey: LIGAMFGPWSKZAA-VQONQEDTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.48
• 重原子数：
  59.0
• 可旋转键数：
  42.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  130.87
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为产物：
  描述：

  1-{[(5S)-2-hydroxy-2-oxido-1,4,2-dioxaphosphinan-5-yl]methyl}-5-azacytosine 2-(hexadecyloxy)ethyl ester 、 二十二酰氯 以 吡啶 为溶剂， 反应 26.0h， 以37%的产率得到N-(5-{[(5S)-2-(2-(hexadecyloxy)ethoxy)-2-oxido-1,4,2-dioxaphosphinan-5-yl]methyl}-4-oxo-4,5-dihydro-1,3,5-triazin-2-yl)docosanamide
  参考文献：
  名称：

  N4-Acyl derivatives as lipophilic prodrugs of cidofovir and its 5-azacytosine analogue, (S)-HPMP-5-azaC: Chemistry and antiviral activity

  摘要：

  Even number fatty acid residues-docosanoyl (behenoyl) and stearoyl were selected for introduction to the N-4-position of (S)-1-[3-hydroxy-2-(phosphonomethoxy) propyl] cytosine) (HPMPC, cidofovir), and its 5-azacytosine counterpart, (S)-1-[3-hydroxy-2-(phosphonomethoxy) propyl] cytosine) (HPMP-5-azaC) with the aim to prepare a new type of lipophilic prodrugs. The study on the influence of these modifications to the stability and biological activity of both antivirals was performed. Different reactivity of both systems towards acylation reactions was also found: the 4-NH2 group of cidofovir was more reactive compared to that of HPMP-5-azaC. In 5-azacytosine derivatives, we found mostly a destabilizing effect of the N-4-acylation but this could be compensated by a positive influence of the esterification of the phosphonate group. Chemical stability of the 5-azacytosine moiety in the HPMP series is increasing in the following order: HPMP-5-azaC < cyclic HPMP-5-azaC < HPMP-5-azaC esters. From the view of prodrug development, the best chemical stability was observed in case of the double prodrug 7: the N-4-behenoyl derivative of the hexadecyloxyethyl ester of cyclic HPMP-5-azaC. The free phosphonic acid (N-4-behenoyl-HPMPC) appeared to be a more potent and selective inhibitor of herpesvirus replication than the parent HPMPC derivative. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.03.031