22639-18-5Relevant articles and documents
Synthesis, physicochemical properties, and biological evaluation of hydroxypyranones and hydroxypyridinones: Novel bidentate ligands for cell- labeling
Ellis, Beverley L.,Duhme, Anne K.,Hider, Robert C.,Hossain, M. Bilayet,Rizvi, Safia,Van Der Helm, Dick
, p. 3659 - 3670 (1996)
The synthesis of a range of hydroxypyranones and hydroxypyridinones with potential for the chelation of indium(III) is described. The crystal structures of two of the indium complexes are presented. The distribution coefficients of the ligands and the corresponding iron(III), gallium(III), and indium(III) complexes are reported. Good linear relationships between the distribution coefficients of the iron and gallium complexes and iron and indium complexes were obtained. In contrast a nonlinear relationship was obtained between the distribution coefficient of the free ligand and the distribution coefficient of the three groups of complexes. This latter relationship was used to identify compounds with optimal cell labeling properties. Two such compounds both 6-(alkoxymethyl)-3-hydroxy-4H-pyran-4- ones have been compared with tropolone for their ability to label human leucocytes with 111In. The leucocyte labeling efficiencies of the selected ligands were greater and the in-vitro plasma stabilities were similar to that of 111In-tropolonate. These results suggest that the new bidentate ligands may offer advantages over those currently used for cell-labeling.
Synthesis, physicochemical characterization, and biological evaluation of 2-(1'-hydroxyalkyl-3-hydroxypyridin-4-ones: Novel iron chelators with enhanced pFe3+ values
Liu, Zu D.,Khodr, Hicham H.,Liu, Ding Y.,Lu, Shu L.,Hider, Robert C.
, p. 4814 - 4823 (2007/10/03)
The synthesis of a range of 2-(1'-hydroxyalkyl)-3-hydroxypyridin-4-ones as bidentate iron(III) chelators with potential for oral administration is described. The pK(a) values of the ligands and the stability constants of their iron(III) complexes have been determined. Results indicate that the introduction of a 1'-hydroxyalkyl group at the 2-position leads to a significant improvement in the pFe3+ values. Such an effect was found to be greater with the hydroxyethyl substituent than with the hydroxy-methyl substituent, particularly in the cases of 1-ethyl-2(1'-hydroxyethyl)-3- hydroxypyridin-4-one (pFe3+ = 21.4) and 1,6-dimethyl-2-(1'-hydroxyethyl)3- hydroxypyridin-4-one (pFe3+ = 21.5) where an enhancement on pFe3+ values in the region of two orders of magnitude is observed, as compared with Deferiprone (1,2-dimethyl-3-hydroxypyridin-4-one) (pFe3+ = 19.4). The ability of these novel 3-hydroxypyridin-4-ones to facilitate the iron excretion in bile was investigated using a [59Fe] ferritin-loaded rat model. Chelators and prodrug chelators possessing high pFe3+ values show great promise in their ability to remove iron under in vivo conditions.
