methyl L-valyl-O-[({[(2S)-1-(4-amino-2-oxopyrimidin-1(2H)-yl)-3-hydroxypropan-2-yl]oxy}methyl)(ethoxy)phosphoryl]-L-serinate | 1312776-44-5

• 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: methyl L-valyl-O-[({[(2S)-1-(4-amino-2-oxopyrimidin-1(2H)-yl)-3-hydroxypropan-2-yl]oxy}methyl)(ethoxy)phosphoryl]-L-serinate
• 英文别名: methyl (2S)-2-[[(2S)-2-amino-3-methylbutanoyl]amino]-3-[[(2S)-1-(4-amino-2-oxopyrimidin-1-yl)-3-hydroxypropan-2-yl]oxymethyl-ethoxyphosphoryl]oxypropanoate
• CAS: 1312776-44-5
• 化学式: C₁₉H₃₄N₅O₉P
• 分子量: 507.481
• InChiKey: FYXORXDMXAUFJA-NRIZNXJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  34
• 可旋转键数：
  16
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  205
• 氢给体数：
  4
• 氢受体数：
  10

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 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 methyl L-valyl-O-[({[(2S)-1-(4-amino-2-oxopyrimidin-1(2H)-yl)-3-hydroxypropan-2-yl]oxy}methyl)(ethoxy)phosphoryl]-L-serinate
  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.