89539-51-5

Upstream product

• 15771-06-9 5-benzyloxy-2-hydroxymethyl-4H-pyran-4-one 
• 74-89-5 methylamine 
• 100-44-7 benzyl chloride 
• 501-30-4 5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one 
• 598-52-7 1-(methyl)-thiourea 

Downstream Products

• 586345-73-5 2-(chloromethyl)-5-(benzyloxy)-1-methylpyridin-4(1H)-one 
• 1429744-62-6 (S)-(5-(benzyloxy)-1-methyl-4-oxo-1,4-dihydropyridin-2-yl)-methyl 2-(benzyloxycarbonyl)-3-phenylpropanoate 

Relevant academic research and scientific papers

New Pqs Quorum Sensing System Inhibitor as an Antibacterial Synergist against Multidrug-Resistant Pseudomonas aeruginosa

Development of new bacterial biofilm inhibitors as antibacterial synergists is an effective strategy to solve the resistance of Pseudomonas aeruginosa. In this paper, a series of 3-hydroxy-pyridin-4(1H)-ones were synthesized and evaluated, and the hit compound (20p) was identified with the effects of inhibiting the production of pyocyanin (IC50 = 8.6 μM) and biofilm formation (IC50 = 4.5 μM). Mechanistic studies confirmed that 20p inhibits the formation of bacterial biofilm by inhibiting the expression of pqsA, blocking pqs quorum sensing system quinolone biosynthesis. Moreover, we systematically investigated the bactericidal effects of combining currently approved antibiotics for CF including tobramycin, ciprofloxacin, and colistin E with 20p, which showed obvious antibacterial synergy to overcome antibiotics resistance in multidrug-resistant P. aeruginosa biofilms. The result indicates that compound 20p may be used in the future as a potentially novel antibacterial synergist candidate for the treatment of P. aeruginosa infections.

N-Propargylamine-hydroxypyridinone hybrids as multitarget agents for the treatment of Alzheimer's disease

AD is a progressive brain disorder. Because of the lack of remarkable single-target drugs against neurodegenerative disorders, the multitarget-directed ligand strategy has received attention as a promising therapeutic approach. Herein, we rationally designed twenty-nine hybrids of N-propargylamine-hydroxypyridinone. The designed hybrids possessed excellent iron-chelating activity (pFe3+ = 17.09–22.02) and potent monoamine oxidase B inhibitory effects. Various biological evaluations of the optimal compound 6b were performed step by step, including inhibition screening of monoamine oxidase (hMAO-B IC50 = 0.083 ± 0.001 μM, hMAO-A IC50 = 6.11 ± 0.08 μM; SI = 73.5), prediction of blood–brain barrier permeability and mouse behavioral research. All of these favorable results proved that the N-propargylamine-hydroxypyridinone scaffold is a promising structure for the discovery of multitargeted ligands for AD therapy.

Pyridone hexa-alkyne amine modified derivative and preparation method and application thereof

The invention relates to a pyridone hexa-alkyne amine modified derivative as shown in a formula (I) and a pharmaceutically acceptable salt thereof, a preparation method thereof, application of the pyridone hexa-alkyne amine modified derivative or the pharmaceutically acceptable salt thereof to preparation of drugs for preventing or treating related diseases, especially Alzheimer's disease and Parkinson's disease, by inhibiting monoamine oxidase, chelating metal iron ions, resisting Abeta and resisting oxidation. According to the invention, a series of novel single-molecule multi-target anti-ADactive compounds are synthesized, and pyridone derivatives with iron ion chelating activity and propynylamine with MAOB inhibitory activity are creatively and organically combined together, so that the compounds have remarkable advantages on Alzheimer's disease with complex pathogenesis; and the combined molecules are far superior to CP20 (deferiprone) in the aspect of iron ion chelating activity.

Synthesis, anti-HIV-1 and antiproliferative evaluation of novel 4-nitroimidazole derivatives combined with 5-hydroxy-4-pyridinone moiety

In an effort to synthesize more effective non-nucleoside reverse transcriptase inhibitors (NNRTIs) against the HIV-1 infection, a new series of novel 4-nitroimidazole derivatives combined with 5-hydroxy-4-pyridinone moiety were designed by molecular docking studies, prepared and characterized by spectroscopic techniques. All the synthesized compounds were in vitro evaluated for their inhibitory effect against the HIV-1 replication in the MT-4 cells. Results showed that none of these synthesized compounds displayed any specific anti HIV-1 activity. Surprisingly, these compounds showed high cytotoxicity against MT-4 cells with low selectivity index (50 = 1.3 μM and EC50 = 1.8 μM respectively).

Functionality study of chalcone-hydroxypyridinone hybrids as tyrosinase inhibitors and influence on anti-tyrosinase activity

In an attempt to synthesise new tyrosinase inhibitors, we designed and synthesised a series of chalcone-hydroxypyridinone hybrids as potential tyrosinase inhibitors adopting strategic modifications of kojic acid. All the newly synthesised compounds were characterised by NMR and mass spectrometry. Initial screening of the target compounds demonstrated that compounds 1a, 1d, and 1n had relatively strong inhibitory activities against tyrosinase monophenolase, with IC50 values of 3.07 ± 0.85, 2.25 ± 0.8 and 2.75 ± 1.19 μM, respectively. The inhibitory activity against monophenolase was 6- to 8-fold higher than that of kojic acid. Compounds 1a, 1d, and 1n also showed inhibition of diphenolase, with IC50 values of 17.05 ± 0.07, 11.70 ± 0.03 and 19.3 ± 0.28 μM, respectively. The inhibition kinetics of diphenolase indicates that compounds 1a and 1d induce reversible inhibition on tyrosinase. Finally, we found that copper coordination should be one of the important inhibitory mechanism of these compounds in tyrosinase.

ALA-HPO hybrid derivative with iron chelating property and PDT activity, preparation method and application thereof

The invention provides an ALA-HPO hybrid derivative shown as a formula (I) or a formula (II), and a preparation method thereof, and application of the ALA-HPO hybrid derivative in preparation of photodynamic therapy drugs. The formula (I) and the formula (II) are defined in the specification.

Novel hydroxypyridinone compounds as well as preparation method and application thereof

The invention belongs to the field of medicines and discloses novel hydroxypyridinone compounds as well as a preparation method and an application thereof. The compounds have the chemical structure shown in a formula (I), (II) or (III), wherein R1 is prop

Design, synthesis and anti-HIV-1 evaluation of a series of 5-hydroxypyridine-4-one derivatives as possible integrase inhibitors

A series of 5-hydroxypyridine-4-one derivatives were synthesized and subjected to HIV-1 replication inhibition assay. Docking studies provide a detailed molecular binding model for this class of compounds interacting with integrase enzyme. All of the deri

Kojic acid derived hydroxypyridinone-chloroquine hybrids: Synthesis, crystal structure, antiplasmodial activity and β-haematin inhibition

Aminochloroquinoline-kojic acid hybrids were synthesized and evaluated for β-haematin inhibition and antiplasmodial activity against drug resistant (K1) and sensitive (3D7) strains of Plasmodium falciparum. Compound 7j was the most potent compound in both strains (IC503D7 = 0.004 μM; IC50K1 = 0.03 μM) and had the best β-haematin inhibition activity (0.07 IC50 equiv vs 1.91 IC 50 equiv for chloroquine). One compound 8c was found to be equipotent in both strains (IC50 = 0.04 μM).

Design and synthesis of hydroxypyridinone-l-phenylalanine conjugates as potential tyrosinase inhibitors

A range of hydroxypyridinone-l-phenylalanine conjugates were synthesized starting from kojic acid. Their tyrosinase activity was determined, and it was found that one of the compounds ((S)-(5-(benzyloxy)-1-octyl-4-oxo-1,4- dihydropyridin-2-yl)methyl 2-amino-3-phenylpropanoate, 5e) showed potent inhibitory effect against mushroom tyrosinase, the IC50 values for monophenolase and diphenolase activities being 12.6 and 4.0 μM, respectively. It was also demonstrated that these conjugates are mixed-type inhibitors, suggesting they could bind to both the free enzyme and the enzyme-substrate complexes. MTT assay indicated that 5e was nontoxic to three cell lines. This compound may find applications in food preservation and cosmetics.