95215-84-2Relevant academic research and scientific papers
Synthesis, physicochemical properties, and biological evaluation of N- substituted 2-alkyl-3-hydroxy-4(1H)-pyridinones: Orally active iron chelators with clinical potential
Dobbin,Hider,Hall,Taylor,Sarpong,Porter,Xiao,Van der Helm
, p. 2448 - 2458 (1993)
The synthesis of a range of novel bidentate ligands containing the chelating moiety 3-hydroxy-4(1H)-pyridinone is described. The pK(a) values of the ligands and the stability constants of their iron(III) complexes have been determined. The crystal structures of one of the ligands and one of the iron(III) complexes are presented. The distribution coefficients of the ligands are reported and are related to the ability of the ligands to remove iron from hepatocytes. The influence of 3-hydroxy-4(1H)-pyridinones on oxidative damage to cells is described. In contrast to the iron chelator in current therapeutic use, desferrioxamine-B, many of the bidentate ligands described in this study are orally active in iron-overloaded mice.
Design and synthesis of N-hydroxyalkyl substituted deferiprone: a kind of iron chelating agents for Parkinson's disease chelation therapy strategy
Zhang, Qingchun,Feng, Shufan,Zhao, Yulian,Jin, Bo,Peng, Rufang
, p. 467 - 478 (2021/05/13)
The blood–brain barrier (BBB) permeability of molecules needs to meet stringent requirements of Lipinski’s rule, which pose a difficulty for the rational design of efficient chelating agents for Parkinson's disease chelation therapy. Therefore, the iron c
Synthesis of new bis(3-hydroxy-4-pyridinone) ligands as chelating agents for uranyl complexation
Jin, Bo,Zheng, Rongzong,Peng, Rufang,Chu, Shijin,Dehaen, Wim
, (2016/04/26)
Five new bis(3-hydroxy-4-pyridinone) tetradentate chelators were synthesized in this study. The structures of these tetradentate chelators were characterized by 1H-NMR, 13C-NMR, FT-IR, UV-vis, and mass spectral analyses. The binding
Design, synthesis, and biological evaluation of aromatic ester prodrugs of 1-(3'-hydroxypropyl)-2-methyl-3-hydroxypyridin-4-one (CP41) as orally active iron chelators
Liu, Zu D.,Liu, Ding Y.,Lu, Shu L.,Hider, Robert C.
, p. 461 - 470 (2007/10/03)
In order to improve chelation efficacy and to minimise toxicity, eleven aromatic ester prodrugs of 1-(3'-hydroxypropyl)-2-methyl-3-hydroxypyridin-4- one (CP41) have been synthesised. The distribution coefficients of these ester prodrugs between 1-octanol and MOPS buffer pH 7.4 were measured together with their rates of hydrolysis at pH 2 and pH 7.4, in rat blood and liver homogenate. The biliary metabolic profiles of selected ester prodrugs were investigated in rats. The in vivo iron mobilisation efficacy of these ester prodrugs has been compared with that of the parent drug using a 59Fe- ferritin loaded rat model. The hydrolytic rates of these esters vary appreciably, esters with heteroaromatic acid moieties being less stable than the corresponding benzoyl analogues. Many prodrugs were found to enhance the ability of the parent hydroxypyridinone to facilitate 59Fe excretion, the optimal effect being observed with the 4-methylbenzoyl ester derivative 8d. However, not all prodrugs provide an increased efficacy, indicating that lipophilicity is not the only factor which influences drug efficacy. Furthermore no clear correlation between lipophilicity, susceptibility towards hydrolysis and efficacy was detected.
Synthesis of N-Substituted 3-Hydroxy-2-methyl-4-pyridones and -pyridonimines
Faerber, M.,Osiander, H.,Severin, T.
, p. 947 - 956 (2007/10/02)
Carbohydrates with 1,4-glycoside bonds like maltose, lactose, dextrin or strach react with primary amines as well as amino acids or proteins to give i.e. 3-hydroxy-2-methyl-4-pyridones 5 and 3-hydroxy-2-methyl-4-pyridonimines 7.A generally applicable synt
