1-[3'-(pivaloyloxy)propyl]-2-methyl-3-hydroxy-4(1H)-pyridinone | 189017-72-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-[3'-(pivaloyloxy)propyl]-2-methyl-3-hydroxy-4(1H)-pyridinone
• 英文别名: CP165；3-(3-Hydroxy-2-methyl-4-oxopyridin-1-yl)propyl 2,2-dimethylpropanoate
• CAS: 189017-72-9
• 化学式: C₁₄H₂₁NO₄
• 分子量: 267.325
• InChiKey: JIKFJIOYCMQBNK-UHFFFAOYSA-N

物化性质

• 沸点：
  385.9±42.0 °C(Predicted)
• 密度：
  1.143±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-[2-methyl-3-benzyloxypyridin-4(1H)-one-1-yl]-1-propanol 在 吡啶 、 水 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-[3'-(pivaloyloxy)propyl]-2-methyl-3-hydroxy-4(1H)-pyridinone
  参考文献：
  名称：

  Synthesis, physicochemical properties and biological evaluation of ester prodrugs of 3-hydroxypyridin-4-ones: design of orally active chelators with clinical potential

  摘要：

  The synthesis of a range of hydrophobic ester prodrugs of 3-hydroxypyridin-4-ones with potential for oral administration is described. The distribution coefficient values of a range of these ester prodrugs and the corresponding alcohols in 1-octanol and MOPS buffer FH 7.4 are presented together with their rates of hydrolysis at pH 2, pH 7.4, in rat blood and liver homogenate. In vivo iron mobilisation efficacy of the pivaloyl and benzoyl prodrugs has been compared with their parent drugs using a Fe-59-ferritin loaded rat model. Both classes of prodrug enhanced the ability of the parent hydroxypyridinone to facilitate the excretion of Fe-59. The influence of the pivaloyl function was more marked than that of the benzoyl function. The optimal effect was observed with 1-[2'-(pivaloyloxy)ethyl]-2-methyl-3-hydroxy-4(1H)-pyridinone 25. However, not all the prodrugs provide increased efficacy which suggests that lipophilicity is not the only factor which influences the drug efficacy. The metabolism of the compound may have a dominating influence on the overall efficacy. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(99)80097-x

文献信息

• Synthesis, physicochemical properties and biological evaluation of ester prodrugs of 3-hydroxypyridin-4-ones: design of orally active chelators with clinical potential
  作者：Bijaya L Rai、Zu Dong Liu、Ding Yong Liu、Shu Li Lu、Robert C Hider

  DOI：10.1016/s0223-5234(99)80097-x

  日期：1999.6

  The synthesis of a range of hydrophobic ester prodrugs of 3-hydroxypyridin-4-ones with potential for oral administration is described. The distribution coefficient values of a range of these ester prodrugs and the corresponding alcohols in 1-octanol and MOPS buffer FH 7.4 are presented together with their rates of hydrolysis at pH 2, pH 7.4, in rat blood and liver homogenate. In vivo iron mobilisation efficacy of the pivaloyl and benzoyl prodrugs has been compared with their parent drugs using a Fe-59-ferritin loaded rat model. Both classes of prodrug enhanced the ability of the parent hydroxypyridinone to facilitate the excretion of Fe-59. The influence of the pivaloyl function was more marked than that of the benzoyl function. The optimal effect was observed with 1-[2'-(pivaloyloxy)ethyl]-2-methyl-3-hydroxy-4(1H)-pyridinone 25. However, not all the prodrugs provide increased efficacy which suggests that lipophilicity is not the only factor which influences the drug efficacy. The metabolism of the compound may have a dominating influence on the overall efficacy. (C) Elsevier, Paris.