propan-2-yl (2S)-2-[[(2R)-2-amino-3-methylbutanoyl]amino]-3-[[(5S)-5-[(4-amino-2-oxopyrimidin-1-yl)methyl]-2-oxo-1,4,2lambda5-dioxaphosphinan-2-yl]oxy]propanoate | 1192360-48-7

• 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: propan-2-yl (2S)-2-[[(2R)-2-amino-3-methylbutanoyl]amino]-3-[[(5S)-5-[(4-amino-2-oxopyrimidin-1-yl)methyl]-2-oxo-1,4,2lambda5-dioxaphosphinan-2-yl]oxy]propanoate
• 英文别名: propan-2-yl (2S)-2-[[(2R)-2-amino-3-methylbutanoyl]amino]-3-[[(5S)-5-[(4-amino-2-oxopyrimidin-1-yl)methyl]-2-oxo-1,4,2λ5-dioxaphosphinan-2-yl]oxy]propanoate
• CAS: 1192360-48-7
• 化学式: C₁₉H₃₂N₅O₈P
• 分子量: 489.466
• InChiKey: CIXBUVQGPYKCND-IRRDFLNTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  185
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  propan-2-yl (2S)-2-[[(2R)-2-amino-3-methylbutanoyl]amino]-3-[[(5S)-5-[(4-amino-2-oxopyrimidin-1-yl)methyl]-2-oxo-1,4,2lambda5-dioxaphosphinan-2-yl]oxy]propanoate 、 三氟乙酸 以 乙腈 为溶剂， 反应 18.0h， 以33%的产率得到propan-2-yl D-valyl-O-[({[(2S)-1-(4-amino-2-oxopyrimidin-1(2H)-yl)-3-hydroxy-propan-2-yl]oxy}methyl)(hydroxy)phosphoryl]-L-serinate trifluoroacetate
  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