958753-83-8

Upstream product

• 1064077-28-6 3-(benzyloxy)-6-methyl-4-oxo-1,4-dihydropyridine-2-carboxylic acid 
• 501-30-4 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one 
• 7559-81-1 chlorokojic acid 
• 100-44-7 benzyl chloride 
• 111782-87-7 3-(benzyloxy)-2-ethyl-4H-pyran-4-one 
• 100397-13-5 5-(benzyloxy)-2-methyl-4H-pyran-4-one 

Downstream Products

• 95264-52-1 5-hydroxy-2-methyl-4(1H)-pyridone 
• 1259499-10-9 5-(benzyloxy)-3-chloro-1,2-dimethylpyridin-4(1H)-one 
• 1259499-08-5 5-(benzyloxy)-3-chloro-2-methylpyridin-4(1H)-one 

Relevant academic research and scientific papers

Design, synthesis and biological evaluation of hydroxypyridinone-coumarin hybrids as multimodal monoamine oxidase B inhibitors and iron chelates against Alzheimer's disease

A series of hybrids of hydroxypyridinone and coumarin were rationally designed, synthesized and biologically evaluated for their iron ion chelating and MAO-B inhibitory activities. Most of the compounds displayed excellent iron ion chelating effects and moderate to good anti-MAO-B activities. Compound 27a exhibited the most potent activity against MAO-B, with an IC50 value of 14.7 nM. Importantly, 27a showed good U251 cell protective effect and significantly ameliorated the cognitive dysfunction of scopolamine-induced AD mice. Moreover, molecular docking was performed to elucidate the probable ligand-receptor interaction, and the structure-activity relationships were also summarized.

Systematic comparison of the mono-, dimethyl-and trimethyl 3-hydroxy-4(1H)-pyridones-Attempted optimization of the orally active iron chelator, deferiprone

A range of close analogues of deferiprone have been synthesised. The group includes mono-, di-and trimethyl-3-hydroxy-4(1H)-pyridones. These compounds were found to possess similar pFe3+ values to that of deferiprone, with the exception of the 2.5-dimethylated derivatives. Surprisingly the NHcontaining hydroxy-4(1H)-pyridones were found to be marginally more lipophilic than the corresponding N-Me containing analogues. This same group are also metabolised less efficiently by Phase 1 hydroxylating enzymes than the corresponding N-Me analogues. As result of this study, three compounds have been identified for further investigation centred on neutropenia and agranulocytosis.

Prediction of 3-hydroxypyridin-4-one (HPO) log K1 values for Fe(iii)

As a means to aid in the design of 3-hydroxypyridin-4-ones (HPOs) intended for use as therapeutic Fe3+ chelating agents, a novel methodology has been developed using quantum mechanical (QM) calculations for predicting the iron binding affinities of the compounds (more specifically, their log K 1 values). The reported/measured HPO log K1 values were verified through their correlation with the corresponding sum of the compounds' ligating group pKa values. Using a training set of eleven HPOs with known log K1 values, reliable predictions are shown to be obtained with QM calculations using the B3LYP/6-31+G(d)/CPCM model chemistry (with Bondi radii, and water as solvent). With this methodology, the observed log K 1 values for the training set compounds are closely matched by the predicted values, with the correlation between the observed and predicted values giving r2 = 0.9. Predictions subsequently made by this method for a test set of 42 HPOs of known log K1 values gave predicted values accurate to within ±0.32 log units. In order to further investigate the predictive power of the method, four novel HPOs were synthesised and their log K1 values were determined experimentally. Comparison of these predicted log K1 values against the measured values gave absolute deviations of 0.22 (13.87 vs. 14.09), 0.02 (14.31 vs. 14.29), 0.12 (14.62 vs. 14.50), and 0.13 (15.04 vs. 15.17). The prediction methodology reported here is the first to be provided for predicting the absolute log K1 values of iron-chelating agents in the absence of pKa values.

Fluorinated derivatives of deferiprone

The present invention relates to novel derivatives of deferiprone. In particular, the present invention relates to fluorinated derivatives of deferiprone or pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising same, processes for the manufacture thereof and their use in the treatment of neurodegenerative diseases caused by the presence of free iron or iron accumulation in neural tissues and in diseases wherein excess iron must be removed or redistributed.