5'-O-(piperazinocarbonyl)-3'-azido-3'-deoxythymidine | 870997-34-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 5'-O-(piperazinocarbonyl)-3'-azido-3'-deoxythymidine
• 英文别名: [(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methyl piperazine-1-carboxylate；[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl piperazine-1-carboxylate
• CAS: 870997-34-5
• 化学式: C₁₅H₂₁N₇O₅
• 分子量: 379.376
• InChiKey: PXOHLOWGTSZWLA-QJPTWQEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  哌嗪 、 以 1,4-二氧六环 为溶剂， 反应 18.0h， 以0.84 g的产率得到5'-O-(piperazinocarbonyl)-3'-azido-3'-deoxythymidine
  参考文献：
  名称：

  Synthesis and Anti-HIV Properties of New Carbamate Prodrugs of AZT

  摘要：

  A series of new 5′‐O‐carbamate prodrugs of AZT have been prepared. The stability in biological media, anti‐HIV properties and pharmacokinetic parameters in dogs were evaluated. The compounds display moderate anti‐HIV activity in cell culture. After oral administration of carbamate IV in dogs, both intact prodrug IV and released AZT were discovered in dog blood. Pharmacokinetic parameters of the compound IV were estimated. Half‐life (T1/2) of AZT released after oral administration of IV in dogs was close to that after administration of AZT itself, and time to the maximum concentration (Tmax) of AZT released from IV was two and three times longer compared with that of AZT and H‐phosphonate AZT, respectively. Acute toxicity was more than five times less if compared with AZT. As a result, we consider this series of carbamate derivatives of AZT as perspective for development of anti‐HIV agents.

  DOI：

  10.1111/cbdd.12047

文献信息

• Synthesis and Anti-HIV Properties of New Carbamate Prodrugs of AZT
  作者：Pavel N. Solyev、Alexander V. Shipitsin、Inna L. Karpenko、Dmitry N. Nosik、Ludmila B. Kalnina、Sergey N. Kochetkov、Marina K. Kukhanova、Maxim V. Jasko

  DOI：10.1111/cbdd.12047

  日期：2012.12

  A series of new 5′‐O‐carbamate prodrugs of AZT have been prepared. The stability in biological media, anti‐HIV properties and pharmacokinetic parameters in dogs were evaluated. The compounds display moderate anti‐HIV activity in cell culture. After oral administration of carbamate IV in dogs, both intact prodrug IV and released AZT were discovered in dog blood. Pharmacokinetic parameters of the compound IV were estimated. Half‐life (T1/2) of AZT released after oral administration of IV in dogs was close to that after administration of AZT itself, and time to the maximum concentration (Tmax) of AZT released from IV was two and three times longer compared with that of AZT and H‐phosphonate AZT, respectively. Acute toxicity was more than five times less if compared with AZT. As a result, we consider this series of carbamate derivatives of AZT as perspective for development of anti‐HIV agents.