ethyl ({[(2S)-1-(4-amino-2-oxopyrimidin-1(2H)-yl)-3-hydroxypropan-2-yl]oxy}methyl)phosphonic acid | 1312776-50-3

• 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: ethyl ({[(2S)-1-(4-amino-2-oxopyrimidin-1(2H)-yl)-3-hydroxypropan-2-yl]oxy}methyl)phosphonic acid
• 英文别名: 1-((S)-3-Hydroxy-2-(O-ethylphosphonomethoxy)propyl)cytosine；[(2S)-1-(4-amino-2-oxopyrimidin-1-yl)-3-hydroxypropan-2-yl]oxymethyl-ethoxyphosphinic acid
• CAS: 1312776-50-3
• 化学式: C₁₀H₁₈N₃O₆P
• 分子量: 307.243
• InChiKey: VLXLHNRGQDFHAA-QMMMGPOBSA-N

物化性质

• 沸点：
  539.4±60.0 °C(Predicted)
• 密度：
  1.54±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  6

安全信息

• WGK Germany：
  3

反应信息

• 作为产物：
  描述：

  diethyl (S)-(((1-(4-benzamido-2-oxopyrimidin-1(2H)-yl)-3-(trityloxy)propan-2-yl)oxy)methyl)phosphonate 在 三氟乙酸 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 16.0h， 生成 ethyl ({[(2S)-1-(4-amino-2-oxopyrimidin-1(2H)-yl)-3-hydroxypropan-2-yl]oxy}methyl)phosphonic acid
  参考文献：
  名称：

  Synthesis, transport and antiviral activity of Ala–Ser and Val–Ser prodrugs of cidofovir

  摘要：

  We report the synthesis and biological evaluation of Ala-(Val-)L-Ser-CO(2)R prodrugs of 1, where a dipeptide promoiety is conjugated to the P(OH) 2 group of cidofovir (1) via esterification by the Ser side chain hydroxyl group and an ethyl group (4 and 5) or alone (6 and 7). In a murine model, oral administration of 4 or 5 did not significantly increase total cidofovir species in the plasma compared to 1 or 2, but 7 resulted in a 15-fold increase in a rat model and had an in vitro EC(50) value against human cytomegalovirus comparable to 1. Neither 6 nor 7 exhibited toxicity up to 100 mu M in KB or HFF cells. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.126

文献信息

• Synthesis, transport and antiviral activity of Ala–Ser and Val–Ser prodrugs of cidofovir
  作者：Larryn W. Peterson、Jae-Seung Kim、Paul Kijek、Stefanie Mitchell、John Hilfinger、Julie Breitenbach、Kathy Borysko、John C. Drach、Boris A. Kashemirov、Charles E. McKenna

  DOI：10.1016/j.bmcl.2011.04.126

  日期：2011.7

  We report the synthesis and biological evaluation of Ala-(Val-)L-Ser-CO(2)R prodrugs of 1, where a dipeptide promoiety is conjugated to the P(OH) 2 group of cidofovir (1) via esterification by the Ser side chain hydroxyl group and an ethyl group (4 and 5) or alone (6 and 7). In a murine model, oral administration of 4 or 5 did not significantly increase total cidofovir species in the plasma compared to 1 or 2, but 7 resulted in a 15-fold increase in a rat model and had an in vitro EC(50) value against human cytomegalovirus comparable to 1. Neither 6 nor 7 exhibited toxicity up to 100 mu M in KB or HFF cells. (C) 2011 Elsevier Ltd. All rights reserved.