216581-63-4Relevant academic research and scientific papers
Orally active iron (III) chelators
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Page column 26, (2008/06/13)
A novel 3-hydroxypyridin-4-one compound of formula I is provided wherein R is hydrogen or a group that is removed by metabolism in vivo to provide the free hydroxy compound, R1 is an aliphatic hydrocarbon group or an aliphatic hydrocarbon group substituted by a hydroxy group or a carboxylic acid ester, sulpho acid ester or a C1-6 alkoxy, C6-aryloxy or C7-10aralkoxy ether thereof, R3 is selected from hydrogen and C1-6alkyl; and R4 is selected from hydrogen, C1-6alkyl and a group as described for R2; characterised in that R2 is selected from groups —CONH—R5??(i) —CH2NHCO—R5??(ii) —SO2NH—R5??(iii) —CH2NHSO2—R5??(iv) —CR6R6OR7??(v) —CONHCOR5??(viii) ?wherein R5 is selected from hydrogen and optionally hydroxy, alkoxy, or aralkoxy substituted C1-13 alkyl, aryl and C71-13 aralkyl, R6 is independently selected from hydrogen, C1-13 alkyl, aryl and C7-13 aralkyl, and R7 is selected from hydrogen, C1-13 alkyl, aryl and C7-13 aralkyl or a pharmaceutically acceptable salt of any such compound with the proviso that when R7 is hydrogen, R6 is not selected from aryl and with the proviso that the compound is not 1-ethyl-2-(1′-hydroxyethyl)-3-hydroxypyridin-4-one.
Orally active iron (III) chelators
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, (2008/06/13)
A compound of formula I wherein R is hydrogen or a group that is removed by metabolism in vivo to provide the free hydroxy compound, R1is an aliphatic hydrocarbon group or an aliphatic hydrocarbon group substituted by a hydroxy group or a carboxylic acid ester, sulpho acid ester or a C1-6alkoxy, C6-aryloxy or C7-10aralkoxy ether thereof, and R3is selected from hydrogen and C1-6alkyl; characterized in that R2is selected from groups (i) —CONH—R5(ii)—CR6R6OR7(iii) —CONHCOR5and (iv) —CON(CnH2n+1)2 R4is selected from hydrogen, C1-6alkyl and a group as described for R2; R5is selected from hydrogen and optionally hydroxy, alkoxy, aryloxy or aralkoxy substituted C1-13alkyl, aryl and C7-13alkyl R6is independently selected from hydrogen and C1-13alkyl, R7is selected from hydrogen, C1-13alkyl, aryl and C7-13aralkyl or a pharmaceutically acceptable salt of any such compound and CnH2n+1is C1-6alkyl with the proviso that the compound is not one of 1-ethyl-2-(1′-hydroxyethyl)-3-hydroxypyridin-4-one and 1-methyl-2-hydroxymethyl-3-hydroxypyridoin-4-one.
Synthesis of 2-amido-3-hydroxypyridin-4(1H)-ones: Novel iron chelators with enhanced pFe3+ values
Liu, Zu D.,Piyamongkol,Liu, Ding Y.,Khodr, Hicham H.,Lu, Shu L.,Hider, Robert C.
, p. 563 - 573 (2007/10/03)
The synthesis of a range of 2-amido-3-hydroxypyridin-4-ones as bidentate iron(III) chelators with potential for oral administration is described. The pKa values of the ligands together with the stability constants of their iron(III) complexes have been determined. Results indicate that the introduction of an amido substituent at the 2-position leads to an appreciable enhancement of the pFe3+ values. 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. The optimal effect was observed with the N-methyl amido derivative 15b, which has an associated pFe3+ value of 21.7, more than two orders of magnitude higher than that of deferiprone (1,2-dimethyl-3-hydroxypyridin-4-one) 1a (pFe3+=19.4). Dose response studies suggest that chelators with high pFe3+ values scavenge iron more effectively at lower doses when compared with simple dialkyl substituted hydroxypyridinones. Copyright
