pentadecanedioyl dizidovudine | 1217192-64-7

• 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: pentadecanedioyl dizidovudine
• CAS: 1217192-64-7
• 化学式: C₃₅H₅₀N₁₀O₁₀
• 分子量: 770.843
• InChiKey: XNMDPJYRQBUTKV-YHRKHFDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.79
• 重原子数：
  55.0
• 可旋转键数：
  22.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  278.3
• 氢给体数：
  2.0
• 氢受体数：
  14.0

反应信息

• 作为产物：
  描述：

  齐多夫定 、 1,15-pentadecanoyl dichloride 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 pentadecanedioyl dizidovudine
  参考文献：
  名称：

  Self-assembled drug delivery systems. Part 5: Self-assemblies of a bolaamphiphilic prodrug containing dual zidovudine

  摘要：

  A bolaamphiphilic prodrug containing dual zidovudine, pentadecanedioyl dizidovudine (PDDZ), was prepared. The vesicular self-assemblies were formed in aqueous media through injecting the methanol solution of PDDZ into water. Hydrophobic interaction between lipid chains should drive molecular self-assembly. The nonionic surfactant, Tween 20, was used to increase the physical stability of self-assemblies because the surfactant micelles could prevent the assemblies from aggregating. The doping hydroxylpropylmethylcellulose (HPMC) slowed down the degradation of prodrugs due to adsorption,The self-assemblies were nanoscale with the mean particle size of 156 nm. Degradation of PDDZ was very slow in buffered solutions, but very rapid in enzyme and plasma, and the parent drug zidovudine (AZT) was the unique product. PDDZ self-assemblies showed strong anti-HIV activity on MT4 cell model. The 50% effective concentration (EC50) of PDDZ was 5 nM, equal to that of AZT. PDDZ was rapidly eliminated from circulation and mainly distributed into liver, spleen and testis followed by the rapid production of AZT after intravenous administration of the self-assemblies to rabbits. Macrophages in liver, spleen and testis are the reservoir of HIV so that the macrophage targeting effect of PDDZ self-assemblies would benefit to anti-HIV therapy. The self-assemblies composed of bolaamphiphilic PDDZ are a promising self-assembled drug delivery system (SADDS). (C) 2009 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ijpharm.2009.11.018