lithium ethyl ({[(2S)-1-[4-(benzoylamino)-2-oxopyrimidin-1(2H)-yl]-3-(trityloxy)propan-2-yl]oxy}methyl)phosphonate | 1312776-47-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: lithium ethyl ({[(2S)-1-[4-(benzoylamino)-2-oxopyrimidin-1(2H)-yl]-3-(trityloxy)propan-2-yl]oxy}methyl)phosphonate
• CAS: 1312776-47-8
• 化学式: C₃₆H₃₅N₃O₇P*Li
• 分子量: 659.605
• InChiKey: NEGXCXBGTIXUGM-UCRKPPETSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  2.44
• 重原子数：
  48.0
• 可旋转键数：
  15.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  131.81
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  lithium ethyl ({[(2S)-1-[4-(benzoylamino)-2-oxopyrimidin-1(2H)-yl]-3-(trityloxy)propan-2-yl]oxy}methyl)phosphonate 在 ammonium hydroxide 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 methyl L-alanyl-O-[({[(2S)-1-(4-amino-2-oxopyrimidin-1(2H)-yl)-3-hydroxypropan-2-yl]oxy}methyl)(ethoxy)phosphoryl]-L-serinate tris(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
• 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 lithium bromide 作用下， 以 乙腈 为溶剂， 反应 40.0h， 生成 lithium ethyl ({[(2S)-1-[4-(benzoylamino)-2-oxopyrimidin-1(2H)-yl]-3-(trityloxy)propan-2-yl]oxy}methyl)phosphonate
  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