Investigation into the correlation between the structure of hydroxypyridinones and blood-brain barrier permeability

Bidentate hydroxypyridinones are under active development as orally active iron chelators. With applications for the treatment of general body iron overload, for instance with thalassaemia, the distribution of the chelators should be limited to peripheral tissue and they should not enter the central nervous system. This study compares the predictive abilities of LogPoctanol and LogPcyclohexane and reports the existence of good correlations between blood-brain barrier (BBB) permeability and both values for N-alkylpyridinones. 1,omega-Hydroxyalkyl hydroxypyridinones penetrate the BBB much more slowly than the simple 1-alkyl derivatives. This observation is likely to have important toxicological implications.