161175-81-1Relevant articles and documents
Design, synthesis and evaluation of N-basic substituted 3-hydroxypyridin-4-ones: Orally active iron chelators with lysosomotrophic potential
Liu, Zu D.,Khodr, Hicham H.,Lu, Shu L.,Hider, Robert C.
, p. 263 - 272 (2000)
To investigate the possibility of targeting chelators into the lysosomal iron pool, nine bidentate 3-hydroxypyridin-4-ones with basic chains have been synthesized. As the turnover of ferritin iron is centred in the lysosome, such strategy is predicted to increase chelator efficacy of bidentate ligands. The pK(a) values of the ligands together with their distribution coefficients between 1-octanol and 4-morpholinepropane sulphonic acid (MOPS) buffer pH 7.4 have been determined. The in-vivo iron mobilization efficacy of these basic 3-hydroxypyridin-4-ones has been investigated in a 59Fe-ferritin-loaded rat model. No obvious correlation was observed between efficacy and the pK(a) value of the side chain, although those with pK(a) > 7.0 tended to be more efficient than those with pK(a) -1 was more effective than 450 μmol kg-1 deferiprone, the widely adopted clinical dose.
