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Unlocking the Biological Potential of 2-Pyridones: Synthesis, Antioxidant and Antimicrobial Activity of N-Phenacylated 5/6-Chloro-2-pyridones.

AIMS: A simple and efficient synthesis of 14 new (9a-9n) N-phenacyl-2-pyridones with good yields (up to 75%), is reported. The synthesized derivatives were screened for their in vitro radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), their in vitro antimicrobial potential was tested against human pathogenic bacterial strains, including Bacillus cereus, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, as well as the fungal strain Candida albicans. METHODS: All compounds displayed modest antioxidant activity, with compound 9b being the most potent in …

Discovery of Pyridones As Oral AMPK Direct Activators.

AMP-activated protein kinase (AMPK) is an evolutionarily conserved fuel-sensing enzyme that is activated in shortage of energy and suppressed in its surfeit. AMPK activation stimulates fatty acid oxidation, enhances insulin sensitivity, alleviates hyperglycemia and hyperlipidemia, and inhibits proinflammatory changes. Thus, AMPK is a well-received therapeutic target for type 2 diabetes and other metabolic disorders. Here, we will report the discovery of pyrrolopyridone derivatives as AMPK direct activators. We will illustrate the synthesis and structure-activity relationships of the series as

Unexpected T3P-Mediated Enaminoester Cascade Cyclization to Access 4-Pyridones.

The development of novel one-pot cascade protocols for synthesizing biologically significant nitrogen heterocycles plays a vital role in drug discovery and development. We report here a new and unexpected T3P-mediated one-pot transformation of amines and β-ketoesters into 4-pyridones via an enaminoester cascade cyclization process. This method affords structurally diverse and readily multi-tailorable 4-pyridones with up to 99% yields in 1 h at 70 °C, providing rapid access to a pharmaceutically significant heterocyclic motif. Furthermore, this method shows a low E-factor (5.18), a low process …

Energy-Transfer Catalysis Enables the Birch-Type Reduction of 2-Pyridones.

Partially saturated heteroarenes are key intermediates in drug development, as their increased C(sp3) character and inherent synthetic versa … ts remain vastly underexplored. Herein, we describe the triplet sensitized, partial saturation of 2-pyridones and their derivatives, which are known as privileged scaffolds in drug discovery. Our methodology shows exceptional regioselectivity for the Birch-type product and tolerates a vast number of functional groups, bypassing conventional highly reducing …

Recent progress in novel macrolides, quinolones, and 2-pyridones to overcome bacterial resistance.

Macrolides, such as clarithromycin and azithromycin, having good activity against pathogens such as Legionella, Chlamydia, Campylobacter spp, Branhamella spp, Pasteurella multocida and streptococci, have gained wide acceptance for the treatment of both upper and lower respiratory tracts, as well as cutaneous infections. Emergence of bacterial resistance, particularly in gram-positive bacteria, has been observed. Macrolide-resistant Streptococcus pneumoniae and S. pyogenes are found in France and many other countries, resulting in failure of therapy for pneumonia, pharyngitis, and skin infectio

Identification of N1-methyl-2-pyridone-5-carboxamide and N1-methyl-4-pyridone-5-carboxamide as components in urine extracts of individuals consuming coffee.

Caffeine metabolites were extracted from urine samples collected 4 h after consumption of a cup of coffee and were separated by high-performance liquid chromatography (HPLC) on a C18 (5 microm) reverse-phase column using an acetonitrile (5%), acetic acid (0.05%) solution as the mobile phase. The elution profiles indicated the constant presence of a major and a minor components eluting between the caffeine metabolites 5-acetamido-6-formyl-3-methyluracil (AFMU) and 7-methylxanthine (7X) in an approximate nine. A procedure was developed for the isolation of the major component in an apparent pure

Deconstructive Insertion of Oximes into Coumarins: Modular Synthesis of Dihydrobenzofuran-Fused Pyridones.

In the presence of a copper catalyst, a series of oximes undergo deconstructive insertion into coumarins to afford structurally interesting dihydrobenzofuran-fused pyridones in moderate to good yields with good functional group compatibility. The reaction likely involves a radical relay annulation, leading to the ring opening of the lactone moiety of the coumarins, and simultaneous formation of three new bonds. The investigation of photoluminescent properties reveals that several obtained compounds may have potential as fluorescent materials.

Antimalarial 4(1H)-pyridones bind to the Qi site of cytochrome bc1.

Cytochrome bc1 is a proven drug target in the prevention and treatment of malaria. The rise in drug-resistant strains of Plasmodium falciparum, the organism responsible for malaria, has generated a global effort in designing new classes of drugs. Much of the design/redesign work on overcoming this resistance has been focused on compounds that are presumed to bind the Q(o) site (one of two potential binding sites within cytochrome bc1 using the known crystal structure of this large membrane-bound macromolecular complex via in silico modeling. Cocrystallization of the cytochrome bc1 complex with

NacNac-zinc-pyridonate mediated ε-caprolactone ROP.

Herein we report the synthesis, isolation and polymerisation activity of two new zinc compounds based on a 2,6-diisopropylphenyl (Dipp) β-diiminate (NacNac) ligand framework with zinc also ligated by an amidate (2-pyridonate or 6-methyl-2-pyridonate) unit. The compounds crystallised as either monomeric (6-Me-2-pyridonate derivative) or dimeric (2-pyridonate) species, although both were found to be monomeric in solution via1H DOSY NMR spectroscopy, which was supported by DFT calculations. These observations suggest that both complexes initiate ring-opening polymerisation (ROP) through a single-

A 2-pyridone amide inhibitor of transcriptional activity in Chlamydia trachomatis.

Chlamydia trachomatis is a strict intracellular bacterium that causes sexually transmitted infections and eye infections that can lead to life-long sequelae. Treatment options are limited to broad-spectrum antibiotics that disturb the commensal flora and contribute to selection of antibiotic-resistant bacteria. Hence, development of novel drugs that specifically target C. trachomatis would be beneficial. 2-pyridone amides are potent and specific inhibitors of Chlamydia infectivity. The first generation compound KSK120, inhibits the developmental cycle of Chlamydia resulting in reduced infectiv

Thiazolino 2-Pyridone Amide Inhibitors of Chlamydia trachomatis Infectivity.

The bacterial pathogen Chlamydia trachomatis is a global health burden currently treated with broad-spectrum antibiotics which disrupt commensal bacteria. We recently identified a compound through phenotypic screening that blocked infectivity of this intracellular pathogen without host cell toxicity (compound 1, KSK 120). Herein, we present the optimization of 1 to a class of thiazolino 2-pyridone amides that are highly efficacious (EC50 ≤ 100 nM) in attenuating infectivity across multiple serovars of C. trachomatis without host cell toxicity. The lead compound 21a exhibits reduced lipophilici

Solvent-Driven Room-Temperature Curtius Rearrangements to Access Nucleotides Bearing Substituted Fused Pyridones.

The intramolecular Curtius rearrangement suffers from a high reaction temperature, low yields, tedious product isolation, and difficult scal … experiments through a combination of IR and NMR titration. Furthermore, using the substituted fused pyridones as unnatural bases, we can obtain a panel of new nucleotides.

Synthesis and Structure-Activity Relationships of the Novel Antimalarials 5-Pyridinyl-4(1 H)-Pyridones.

Malaria is still one of the most prevalent parasitic infections in the world, with half of the world's population at risk for malaria. The effectiveness of current antimalarial therapies, even that of the most recent class of antimalarial drugs (artemisinin-combination therapies, ACTs), is under continuous threat by the spread of resistant Plasmodium strains. As a consequence, there is still an urgent requirement for new antimalarial drugs. We previously reported the identification of 4(1 H)-pyridones as a novel series with potent antimalarial activities. The low solubility was identified as a…

2-Pyridone as privileged scaffold: Advances in drug design and structural modification.

The 2-pyridone scaffold constitutes a privileged and versatile heterocyclic framework in medicinal chemistry. Existing reviews have largely concentrated on synthetic methodologies, and a comprehensive overview of this scaffold in medicinal chemistry remains lacking. This review systematically surveys the applications of 2-pyridone-based compounds from 2010 to 2026, with an emphasis on design strategies, structure-activity relationships (SAR), druggability optimization, and biological activities. The applications of these derivatives span diverse disease categories, including cancer, infectious

Copper-catalysed radical cascade reaction of N-(2-oxo-2-phenylethyl) substituted 2-pyridones with styrene to access 1,6-carboannulated 2-pyridone scaffolds.

Herein, we present that treating N-(2-oxo-2-phenylethyl) substituted 2-pyridones with styrenes in DMSO/H2O at 120 °C affords 1,6-carboannulated 2-pyridone scaffolds with up to 79% yield. This protocol provides a simple and efficient method for obtaining complicated bicyclic 2-pyridones through a radical cascade reaction. Additionally, we have successfully synthesized 27 target compounds, which confirms the practicality and wide applicability of the proposed reaction.

Fe(III)-Catalyzed Tandem Cyclization of Phenylpropiolamides with 3-Formylchromones for the Construction of 2-Pyridones.

A highly efficient and atom-economic iron(III)-catalyzed three-component heteroannulation reaction between phenylpropiolamides, 3-formylchromones, and water is described for the construction of diversely multifunctionalized 2-pyridones. This protocol allows rapid access to a variety of 2-pyridones bearing an ortho-hydroxybenzoyl and a benzoyl scaffold under operationally simple conditions. The synthetic utility of the synthesized 2-pyridone scaffolds is demonstrated by transformation into biologically interesting complex heterocycles.

Chimeric Pyridone Alkaloids from the Mangrove Endophytic Fungus Aspergillus niger.

Thirty-four chimeric pyridone alkaloids, including twenty-eight new compounds named aspernigrins F1-F8, G1-G5, H1-H7, and I-P (1-28), were isolated from the mangrove endophytic fungus Aspergillus niger H6a, together with six known ones (29-34). The structures of these compounds were elucidated by HRESIMS, NMR spectroscopic data, single-crystal X-ray diffraction analyses, TDDFT-ECD calculations, and chemical methods, including Marfey's derivatization. The structure of 26 contains two units of 2-aminododecanoic acid, whereas those of 27 and 28 not only contain two moieties of 2-aminododecanoic a

Design, synthesis, and evaluation of polycyclic pyridone derivatives as potent influenza inhibitors.

Pandemics caused by influenza viruses remain a serious public health concern worldwide, despite the approval of many antiviral agents, in which baloxavir marboxil (BXM) as the first cap-dependent endonuclease (CEN) inhibitor demonstrates excellent efficacy. Clinical trials have shown that BXM faces emerging resistance (e.g., I38T mutation), compromising its efficacy against variants and urging the development of more effective inhibitors. In this study, a series of novel substituted polycyclic pyridone derivatives were designed and synthesized by replacing the dibenzothiepin scaffold of baloxa

Polynuclear Iron(II) Pyridonates: Synthesis and Reactivity of Fe4 and Fe5 Clusters.

The combination of pyridonate ligands with transition metal ions enables the synthesis of an especially rich set of diverse coordination compounds involving various κ- and μ-bonding modes and higher nuclearities. With iron(II) ions, this chemical space is rather poorly explored beyond some biomimetic models of the pyridone iron-containing hydrogenase. Here, the topologically new Fe5 and Fe4 clusters, Fe5(LH)6[N(SiMe3)2]4 (1) and Fe4(LMe)6[N(SiMe3)2]2 (2), were synthesized (LH = 2-pyridonate; LMe = 6-methyl-2-pyridonate). Complex 1 contained an unprecedented diamondoid Fe@Fe4 tetrahedron with a

Tiazolino 2-Pyridone Amide Isosters в качестве игибиторов хламидийной трахоматичной инфекции.

Хламидиотрахоматис является глобальным медико-санитарным бременем в силу его распространенности как заболевания, передающегося половым путем, и как причинно-следственного агента трахомы глазной инфекции. Недавно мы обнаружили 3-амидо тиазолино 2-пиридон, который смягчал инфекционную инфекцию Т. Трахомати без ущерба для клеточной или коммензальной бактерии. Мы представляем здесь синтез и оценку негидролизируемых изостеров амида, основанных на этом классе, что приводит к высокоэффективным ингибиторам инфекционной активности на основе 1,2,3-триазола (EC50 ≤ 20 nM).

Совпадение в аннотации оригинала
Chlamydia trachomatis is a global health burden due to its prevalence as a sexually transmitted disease and as the causative agent of the eye infection trachoma. We recently discovered 3-amido thiazolino 2-pyridones which attenuated C. trachomatis infectivity without affecting host cell or commensal bacteria viability. We present here the synthesis and evalu…