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- W2043347837 abstract "Abstract 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 pH 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 59 Fe-ferritin loaded rat model. Both classes of prodrug enhanced the ability of the parent hydroxypyridinone to facilitate the excretion of 59 Fe. 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(1 H )-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." @default.
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- W2043347837 date "1999-06-01" @default.
- W2043347837 modified "2023-09-26" @default.
- W2043347837 title "Synthesis, physicochemical properties and biological evaluation of ester prodrugs of 3-hydroxypyridin-4-ones: design of orally active chelators with clinical potential" @default.
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- W2043347837 doi "https://doi.org/10.1016/s0223-5234(99)80097-x" @default.
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