95215-50-2

Upstream product

• 61049-69-2 3-O-benzylmaltol 
• 141-43-5 ethanolamine 
• 118-71-8 Maltol 
• 100-39-0 benzyl bromide 
• 100-44-7 benzyl chloride 
• 95215-49-9 1-acetyl-3-hydroxy-2-methylpyrid-4-one 

Downstream Products

• 874383-28-5 1-[2'-(diethylphosphonomethoxy)ethyl]-2-methyl-3-benzyloxy-4-pyridinone 
• 773835-48-6 1-[2'-(benzoyloxy)ethyl]-2-methyl-3-hydroxy-4(1H)-pyridinone 
• 30652-21-2 CP40 
• 1219111-72-4 3-(benzyloxy)-1-(2-(benzyloxy)ethyl)-2-methylpyridin-4(1H)-one 
• 1219111-74-6 3-(benzyloxy)-1-(2-(benzyloxy)ethyl)-4-oxo-1,4-dihydropyridine-2-carbaldehyde 
• 1219111-68-8 3-(benzyloxy)-1-(2-(benzyloxy)ethyl)-4-oxo-1,4-dihydropyridine-2-carboxylic acid 

Relevant academic research and scientific papers

Design and synthesis of N-hydroxyalkyl substituted deferiprone: a kind of iron chelating agents for Parkinson's disease chelation therapy strategy

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

CN128: A New Orally Active Hydroxypyridinone Iron Chelator

Deferoxamine, deferiprone, and deferasirox are used for the treatment of systemic iron overload, although they possess limitations due to lack of oral activity, lower efficacy, and side effects. These limitations led to a search for an orally active iron chelator with an improved therapeutic index. The lower efficacy of deferiprone is due to rapid glucuronidation, leading to the formation of a nonchelating metabolite. Here, we demonstrate that the influence of metabolism can be reduced by introducing a sacrificial site for glucuronidation. A log P-guided investigation of 20 hydroxpyridinones led to the identification of CN128. The Fe(III) affinity and metal selectivity of CN128 are similar to those of deferiprone, the log P value is more lipophilic, and its iron scavenging ability is superior. Overall, CN128 was demonstrated to be safe in a range of toxicity assessments and is now in clinical trials for the treatment of β-thalassemia after regular blood transfusion.

New polyazamacrocyclic 3-hydroxy-4-pyridinone based ligands for iron depletion antitumor activity

Iron depletion is an efficient strategy for the development of anticancer agents. In an effort to develop efficient chelators, two new 3-hydroxy-4-pyridinone based polyazamacrocycles 1e and 2e were designed and synthesized. A preliminary study of the liga

Synthesis of new bis(3-hydroxy-4-pyridinone) ligands as chelating agents for uranyl complexation

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

Novel 3-hydroxypyridin-4-one hexadentate ligand-based polymeric iron chelator: Synthesis, characterization and antimicrobial evaluation

A novel 3-hydroxypyridin-4-one (HPO) hexadentate monomeric chelator 14 has been synthesized and incorporated into polymers by copolymerization with 2-hydroxyethyl acrylate (HEA), using azobisisobutyronitrile (AIBN) as an initiator. The monomeric chelator was found to possess very high affinity for iron(III), with the log stability constant of the iron complex (log K1) = 33.61 and pFe3+ = 30.37. The iron binding capacity and monomer recovery of the copolymers were determined using spectrophotometry. The in vitro antimicrobial activity of monomeric chelator 14 and polymeric chelator 16-4 against both Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli, Salmonella spp., and Pseudomonas aeruginosa) was evaluated by inhibition zone and minimum inhibitory concentration (MIC) assays, which demonstrated that both monomeric and polymeric chelators possess inhibitory activity. The polymeric chelators possess potential application for the treatment of wound infection.

Design, synthesis and biological evaluation of 5-aminolaevulinic acid/3-hydroxypyridinone conjugates as potential photodynamic therapeutical agents

5-Aminolaevulinic acid (ALA) prodrugs have been widely used in photodynamic therapy (PDT) as precursors to the natural photosensitizer, protoporphyrin IX (PpIX). The main disadvantage of this therapy is that ALA is poorly absorbed by cells due to its high hydrophilicity. In order to improve the therapeutical effect and induce higher yields of PpIX, a range of prodrugs of ALA conjugated to 3-hydroxypyridin-4-ones (HPO) were synthesized. Pharmacokinetic studies indicated that some of the ALA-HPO conjugates are more efficient than ALA for PpIX production in the human breast adenocarcinoma cell line (MDA-MB-468). The intracellular porphyrin fluorescence levels showed good correlation with cellular phototoxicity following light exposure, suggesting the potential application of the ALA-HPO conjugates in photodynamic therapy.

Design, synthesis, and antimicrobial evaluation of hexadentate hydroxypyridinones with high iron(iii) affinity

A range of hexadentate 3-hydroxypyridin-4-ones (HPOs) with high affinity for iron(III) has been synthesized. The log stability constants of two HPO-iron complexes (logK1) were determined to be over 34, and pFe values of the two HPOs were determined to be over 31. Antimicrobial assay indicated that they are able to markedly inhibit the growth of both Gram-positive and Gram-negative bacteria. Compounds 14a and 14e were found to exhibit the strongest inhibitory activity against Staphyloccocus aureus, Bacillus subtilis, Pseudomonas aeruginosa, and Escherichia coli, with MIC values of 8, 8, 16, and 8 lg/mL, respectively. These results indicate that hexadentate 3-hydroxypyridin-4-ones have potential application as antimicrobial agents, especially in the treatment of wound infection.

In vitro studies of lanthanide complexes for the treatment of osteoporosis

Lanthanide ions, Ln(iii), are of interest in the treatment of bone density disorders because they are found to accumulate preferentially in bone (in vivo), have a stimulatory effect on bone formation, and exhibit an inhibitory effect on bone degradation (in vitro), altering the homeostasis of the bone cycle. In an effort to develop an orally active lanthanide drug, a series of 3-hydroxy-4-pyridinone ligands were synthesized and eight of these ligands (H1 = 3-hydroxy-2-methyl-1-(2-hydroxyethyl)-4-pyridinone, H2 = 3-hydroxy-2-methyl-1- (3-hydroxypropyl)-4-pyridinone, H3 = 3-hydroxy-2-methyl-1-(4-hydroxybutyl)-4- pyridinone, H4 = 3-hydroxy-2-methyl-1-(2-hydroxypropyl)-4-pyridinone, H5 = 3-hydroxy-2-methyl-1-(1-hydroxy-3-methylbutan-2-yl)-4-pyridinone, H6 = 3-hydroxy-2-methyl-1-(1-hydroxybutan-2-yl)-4-pyridinone, H7 = 1-carboxymethyl-3-hydroxy-2-methyl-4-pyridinone, H8 = 1-carboxyethyl-3-hydroxy- 2-methyl-4-pyridinone) were coordinated to Ln3+ (Ln = La, Eu, Gd, Lu) forming stable tris-ligand complexes (LnL3, L = 1-, 2-, 3-, 4-, 5-, 6-, 7- and 8-). The dissociation (pKan) and metal ligand stability constants (log βn) of the 3-hydroxy-4- pyridinones with La3+ and Gd3+ were determined by potentiometric titrations, which demonstrated that the 3-hydroxy-4-pyridinones form stable tris-ligand complexes with the lanthanide ions. One phosphinate-EDTA derivative (H5XT = bis[[bis(carboxymethyl)amino]methyl]phosphinate) was also synthesized and coordinated to Ln3+ (Ln = La, Eu, Lu), forming the potassium salt of [Ln(XT)]2-. Cytotoxicity assays were carried out in MG-63 cells; all the ligands and metal complexes tested were observed to be non-toxic to this cell line. Studies to investigate the toxicity, cellular uptake and apparent permeability (Papp) of the lanthanide ions were conducted in Caco-2 cells where it was observed that [La(XT)] 2- had the greatest cell uptake. Binding affinities of free lanthanide ions (Ln = La, Gd and Lu), metal complexes and free 3-hydroxy-4-pyridinones with the bone mineral hydroxyapatite (HAP) are high, as well as moderate to strong for the free ligand with the bone mineral depending on the functional group.

PROCESS FOR THE PREPARATION OF SUBSTITUTED PYRIDONE CARBOXYLIC ACIDS

The present invention relates to methods for the preparation of pyridone carboxylic acids for use as intermediates in the preparation of various synthetic organic compounds. The pyridone carboxylic acids can for example be used as intermediates in the production of potent antitumor agents, antifungal agents, antiviral agents, psychotherapeutic agents or contrast imaging agents for MRI.

Synthesis and antiviral evaluation of cyclic and acyclic 2-methyl-3-hydroxy-4-pyridinone nucleoside derivatives

A series of cyclic and acyclic nucleoside analogues derived from 3-hydroxy-4-pyridinone were synthesized using the Vorbrüggen reaction. Iron chelation studies, and antiviral evaluation against a broad panel of viruses, were performed. The pKa value of ligand 25 and the stability constant of the corresponding iron-(III) complex were compared to those of deferiprone. The pFe3+ values were found to be similar. Some compounds showed moderate activity against both wild-type HSV-1 and HSV-2, as well as against a thymidine kinase deficient strain of HSV-1. These results suggest a novel mode of action for this group of nucleoside analogues.