143489-89-8

Upstream product

• 61049-69-2 3-O-benzylmaltol 
• 56-12-2 4-amino-n-butyric acid 
• 100-44-7 benzyl chloride 
• 61892-88-4 2-hydroxy-3-methyl-4H-pyran-4-one 
• 118-71-8 Maltol 

Downstream Products

• 213026-65-4 4-(3-Benzyloxy-2-methyl-4-oxo-4H-pyridin-1-yl)-butyric acid 2,5-dioxo-pyrrolidin-1-yl ester 
• 1429744-78-4 N-(4-(benzo[d]thiazol-2-ylmethyl)phenyl)-4-(3-(benzyloxy)-2-methyl-4-oxopyridin-1(4H)-yl)butanamide 
• 1429744-82-0 N-(4-(benzo[d]thiazol-2-ylmethyl)phenyl)-4-(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)butanamide 

Relevant academic research and scientific papers

Multifunctional iron-chelators with protective roles against neurodegenerative diseases

The multifactorial nature of Alzheimer's disease (AD), and the absence of a disease modifying drug, makes the development of new multifunctional drugs an attractive therapeutic strategy. Taking into account the hallmarks of AD patient brains, such as low levels of acetylcholine, misfolding of proteins and associated beta-amyloid (Aβ) aggregation, oxidative stress and metal dyshomeostasis, we have developed a series of compounds that merge three different approaches: metal attenuation, anti-Aβ aggregation and anti-acetylcholinesterase activity. Therefore, 3-hydroxy-4-pyridinone (3,4-HP) and benzothiazole molecular moieties were selected as starting frameworks due to their well known affinity for iron and Aβ peptides, respectively. The linkers between these two main functional groups were selected on the basis of virtual screening, so that the final molecule could further inhibit the acetylcholinesterase, responsible for the cholinergic losses. We describe herein the design and synthesis of the new hybrid compounds, followed by the assessment of solution properties, namely iron chelation and anti-oxidant capacity. The compounds were bioassayed for their capacity to inhibit AChE, as well as self- and Zn mediated-Aβ1-42 aggregation. Finally, we assessed their effects on the viability of neuronal cells stressed with Aβ42.

Synthesis, physicochemical properties, and evaluation of N-substituted- 2-alkyl-3-hydroxy-4(1H)-pyridinones

The synthesis of a range of 3-hydroxy-4(1H)-pyridinones with potential for the chelation of iron(III) is described. The pK(a) values of respective ligands and the stability constants of their iron(III) complexes are presented. The distribution coefficient values of a range of 48 hydroxypyridinones and their corresponding iron(III) complexes between 1- octanol and MOPS buffer (pH 7.4) are reported. The range of log D(complex) values covers 7 orders of magnitude. The results suggest the existence of a biphasic relationship between the distribution coefficient values of the chelator and the corresponding iron(III) complexes. For ligands with a log D(ligand) = -1, a linear relationship exists with a value of the slope 2.53, whereas with ligands with a log D(ligand) 59Fe]ferritin-loaded rat model. Both systems compare the ability of chelators to remove iron from the liver, the prime target organ in thalassemia. The N-(hydroxyalkyl)-3-hydroxypyridin-4-ones are demonstrated to be orally active under the in vivo conditions adopted. Thus both 1- (hydroxyalkyl)- and 1-(carboxyalkyl)pyridinones are able to remove iron from the liver. Although 1-(carboxyalkyl)hydroxypyridinones are: active, they do not demonstrate any clear advantage over Deferiprone (1,2-dimethyl-3- hydroxypyridin-4-one). Indeed 1-(hydroxyalkyl)hydroxypyridinones which are known to be rapidly converted to 1-(carboxYalkyl)hydroxypyridinones are also marginally superior to Deferiprone. In contrast, 2-ethyl-1-(2'- hydroxyethyl)3-hydroxypyridin-4-one, which is not metabolized to the corresponding (carboxyalkyl)hydroxypyridinone, was found to be superior to Deferiprone and therefore deserves further consideration as an orally active iron chelator with potential for the treatment of iron overload associated with transfusion-dependent thalassemia.

Synthesis, physicochemical properties, and biological evaluation of N- substituted 2-alkyl-3-hydroxy-4(1H)-pyridinones: Orally active iron chelators with clinical potential

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.

3-hydroxypyridin-4-one derivatives as pharmaceutical compositions

3-Hydroxypyridin-4-ones of formula (I) in which R1 is selected from hydrogen, C1 3 aliphatic hydrocarbon groups, 2-hydroxyethyl, C1 4 aliphatic hydrocarbon groups substituted by a single carboxy, sulp