1-(5-O-{hydroxy[2-(octadecyloxy)ethoxy]phosphoryl}-2,3-O-isopropylidene-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide | 1166376-42-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 三唑核糖核苷和核糖核苷酸
• 英文名称: 1-(5-O-{hydroxy[2-(octadecyloxy)ethoxy]phosphoryl}-2,3-O-isopropylidene-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide
• 英文别名: [(3aR,4R,6R,6aR)-4-(3-carbamoyl-1,2,4-triazol-1-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methyl 2-octadecoxyethyl hydrogen phosphate
• CAS: 1166376-42-6
• 化学式: C₃₁H₅₇N₄O₉P
• 分子量: 660.789
• InChiKey: ZHFSXJYWAIXORN-NSBPXKJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  45
• 可旋转键数：
  26
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  167
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  1-(5-O-{hydroxy[2-(octadecyloxy)ethoxy]phosphoryl}-2,3-O-isopropylidene-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide 在 水 、 三氟乙酸 作用下， 反应 0.75h， 以93%的产率得到1-(5-O-{hydroxy[2-(octadecyloxy)ethoxy]phosphoryl}-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide
  参考文献：
  名称：

  Synthesis and evaluation of a new phosphorylated ribavirin prodrug

  摘要：

  Ribavirin is an important broad-spectrum antiviral drug. However, its utilization can be limited by its potential to cause hemolytic anemia as well as its variability in dosing levels and efficacy outcomes. To overcome these issues, we report on a new alkoxyalkylphosphodiester prodrug of ribavirin (2) that is designed to release the active ribavirin-monophosphate species selectively in nucleated cells while limiting its exposure in anucleated red blood cells (RBCs). Prodrug 2 displays improved in vitro antiviral activity against the hepatitis C virus replicon and influenza virus. Unlike ribavirin, prodrug 2 does not significantly decrease ATP levels in RBCs. Prodrug 2 demonstrates decreased uptake in RBCs but increased uptake in HepG2 hepatocytes when compared to ribavirin. In vivo, prodrug 2 is orally bioavailable and well-tolerated in rats in which it is processed to ribavirin and accumulates in the liver. These results indicate that prodrug 2 has the potential for safer, lower, less frequent, and less variable administration than ribavirin. (C) 2013 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.antiviral.2013.04.014
• 作为产物：
  描述：

  1-{5-O-[(2-chlorophenoxy)(2-octadecyloxyethoxy)phosphoryl]-2,3-O-isopropylidene-β-D-ribofuranosyl}-1H-1,2,4-triazole-3-carboxamide 在 syn-2-pyridinealdoxime 、 四甲基胍 作用下， 以 四氢呋喃 为溶剂， 以81%的产率得到1-(5-O-{hydroxy[2-(octadecyloxy)ethoxy]phosphoryl}-2,3-O-isopropylidene-β-D-ribofuranosyl)-1H-1,2,4-triazole-3-carboxamide
  参考文献：
  名称：

  Synthesis and evaluation of a new phosphorylated ribavirin prodrug

  摘要：

  Ribavirin is an important broad-spectrum antiviral drug. However, its utilization can be limited by its potential to cause hemolytic anemia as well as its variability in dosing levels and efficacy outcomes. To overcome these issues, we report on a new alkoxyalkylphosphodiester prodrug of ribavirin (2) that is designed to release the active ribavirin-monophosphate species selectively in nucleated cells while limiting its exposure in anucleated red blood cells (RBCs). Prodrug 2 displays improved in vitro antiviral activity against the hepatitis C virus replicon and influenza virus. Unlike ribavirin, prodrug 2 does not significantly decrease ATP levels in RBCs. Prodrug 2 demonstrates decreased uptake in RBCs but increased uptake in HepG2 hepatocytes when compared to ribavirin. In vivo, prodrug 2 is orally bioavailable and well-tolerated in rats in which it is processed to ribavirin and accumulates in the liver. These results indicate that prodrug 2 has the potential for safer, lower, less frequent, and less variable administration than ribavirin. (C) 2013 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.antiviral.2013.04.014

文献信息

• ANTIVIRAL COMPOUNDS
  申请人：Dong Steven

  公开号：US20100298256A1

  公开（公告）日：2010-11-25

  Lipid-modified phosphodiester nucleoside prodrugs are described herein. The prodrugs can be used to treat viral infections and cancer.