216581-52-1Relevant academic research and scientific papers
Amido-3-hydroxypyridin-4-ones as iron(III) ligands
Piyamongkol, Sirivipa,Ma, Yong M.,Kong, Xiao L.,Liu, Zu D.,Aytemir, Mutlu D.,Van Der Helm, Dick,Hider, Robert C.
supporting information; experimental part, p. 6374 - 6381 (2010/11/24)
The synthesis and physicochemical properties of a range of 2and 6-amido-3-hydroxypyridin-4-ones are described. All the amido-substituted 3-hydroxypyridin-4-ones have lower pKa values than 1,2-dimethyl-3-hydr-oxypyridin-4-one (deferiprone). This
CYCLOALKYL DERIVATIVES OF 3-HYDROXY-4-PYRIDINONES
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Page/Page column 21, (2008/06/13)
The present invention provides an cycloalkyl derivative of 3-hydroxy-4-pyridinone which is useful for the chelation of metal ions such as iron. Its preparation and use is described. In particular, the invention concerns the removal of iron in chemical and biological systems including chelating agents having the formula (I); wherein R1 is X with the proviso that R2 is Y;or R1 is T with the proviso that R2 is W; or R1 is X with the proviso that R 2 R5 N when taken together form a heterocyclic ring selected from piperidinyl, morpholinyl, pyrrolidinyl or piperazinyl, wherein the group piperidinyl, morpholinyl, pyrrolidinyl or piperazinyl is either unsubstituted or substituted with one to three C1 to C6 alkyl groups. X is C3-C6 cycloalkyl; Y is selected from the group consisting of C1 to C6 cycloalkyl; C1 to C6 alkyl, and C1 to C6 alkyl monosubstituted with a C3-C6 cycloalkyl; T is C1 to C6 alkyl; W is C3-C6 cycloalkyl; R3 is selected from the group consisting of hydrogen and C1 to C6 alkyl; R4 is selected from the group consisting of hydrogen and C1 to C6 alkyl; R5 is selected from the group consisting of hydrogen and C1 to C6 alkyl; and its pharmaceutically acceptable salt thereof. Pharmaceutical compositions of such compounds are useful in the removal of excess body iron from patients with iron overload diseases.
Orally active iron (III) chelators
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Page column 24, (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.
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
