Pyridone Derivatives Research Articles

Wide-Range Columnar and Lamellar Photoluminescent Liquid-Crystalline Lanthanide Complexes with Mesogenic 4-Pyridone Derivatives.

A series of liquid crystals with various lanthanide ions (EuIII , SmIII , and TbIII ) was designed and prepared starting from the corresponding lanthanide nitrates and N-alkylated 4-pyridone derivatives bearing mesogenic 3,4,5-tris(alkyloxy)benzyl moieties (alkyl=hexyl, octyl, decyl, dodecyl, tetradecyl, or hexadecyl). These new lanthanidomesogens were investigated for their mesogenic properties by a combination of differential scanning calorimetry, polarizing optical microscopy, and temperature-dependent powder X-ray diffraction (XRD). Their thermal stability was assessed by thermogravimetric analysis. All of these complexes show enantiotropic liquid-crystalline behavior with lamellar (SmA) phases in the case of shorter-chain complexes (C6 and C8 ) or hexagonal columnar phases (Colh ) for complexes with longer alkyl chains (C12 , C14 , and C16 ), which were assigned on the basis of their characteristic textures and XRD studies. For complexes with an intermediate number of carbon atoms in the side chains (C10 ), both a lamellar phase at lower temperatures and a Colh phase at higher temperatures were evidenced. In the solid state, all these complexes show characteristic emissions assigned to the corresponding lanthanide ion. In addition, the luminescence decay curves showed single-exponential decays with characteristic times in the millisecond range (0.75-0.90 ms for EuIII , 0.045-0.060 ms for SmIII , and 0.75-1.05 ms for TbIII ).

Structural and optical profile of a multifunctionalized 2-pyridone derivative in a crystal engineering perspective.

The supramolecular structural features of organic molecules are very important with regard to their widespread properties in both solids and solutions. Herein, we describe the synthesis of a novel multifunctional 2-pyridone derivative, namely 6-(4-chlorophenyl)-5-formyl-4-methylsulfanyl-2-oxo-1,2-dihydropyridine-3-carbonitrile, C14H9ClN2O2S, denoted P1, and its structural features were established through X-ray crystallography. A Hirshfeld surface analysis followed by a two-dimensional fingerprint plot analysis was carried out. A frontier molecular orbital investigation and natural bond orbital (NBO) calculations explored the charge-transfer interactions associated with the molecular system. The optical properties of the 2-pyridone derivative were elucidated through UV-Vis absorption and emission spectroscopy, indicating a strong blue emissive nature with a colour purity of 82.5%, a short-lived lifetime and a large Stokes shift. Time-dependent density functional theory (TD-DFT) was used to gain some insight into the absorption behaviour and emissive characteristics of P1.

Efficient synthesis of pyrano[2,3-b]pyridine derivatives using microwave or solar energy

Pyranopyridine derivatives are an important class of heterocyclic compounds due to their biological activities such as antitumor and antibacterial. However, conventional procedures for their synthesis produce large amounts of toxic by-products. Therefore, there is a need to develop simple, efficient and environmentally benign procedures. Here, a one-pot multicomponent protocol is designed for the synthesis of pyrano[2,3-b]pyridone derivatives by reaction of equimolar amounts of 6-hydroxy-1,4-dimethyl-1,2-dihydropyridines, aryl aldehydes and malononitrile, using both microwave heating and solar thermal energy in aqueous EtOH (50%) in the presence of a catalytic amount of K2CO3. The products were obtained in 84–90% yields in 10–20 min by microwave heating, and in 90–96% yields in 2–3 h using solar energy.

An Efficient One‐Pot Synthesis of Highly Substituted Pyridone Derivatives and Their Antimicrobial and Antifungal Activity

A series of carboxamide and cyano functionalized pyridone derivatives 4a–q have been synthesized via one‐pot synthesis of various aldehydes 1a–q, acetoacetanilide 2, and cyanoacetamide 3. The reaction was simple and afforded pyridone derivatives in good yield, 89 to 93%. The novel pyridone derivatives were achieved by Hantzch one‐pot synthesis. Moreover, the synthesized compounds were screened against Gram‐positive and Gram‐negative bacteria and fungi for their activity. Among them, compound 4c shows highest inhibition at 4.25 mm against Staphylococcus aureus and 3.75 mm against Escherichia coli Gram‐positive and Gram‐negative bacteria, respectively.

Thermally induced formal [4+2] cycloaddition of 3-aminocyclobutenones with electron-deficient alkynes: facile and efficient synthesis of 4-pyridones.

A thermally induced novel formal [4+2] cycloaddition of cyclobutenones with electron-deficient alkynes under metal-free conditions has been developed for the first time. The reaction can proceed in a highly regioselective manner and provides a straightforward and efficient method for the synthesis of 4-pyridone derivatives from readily available starting materials in a single step.

L-Proline catalyzed one-pot synthesis of polysubstituted pyridine system incorporating benzothiazole moiety via sustainable sonochemical approach.

The efficient, highly convenient synthesis of polysubstituted pyridine derivatives was established via the reaction of N-(benzothiazol-2-yl)-2-cyanoacetamides with an assortment of arylidene malononitriles and arylidene ethyl cyanoacetates in the presence of l-proline as an efficient organocatalyst for this type of ultrasonic-mediated Michael addition. The mechanistic pathway and factors affecting this reaction were also established. The main characteristics of this procedure are high yields, use of a cost-effective catalyst, and easy work-up and purification.

Tracking the Source of Carbon Dot Photoluminescence: Aromatic Domains versus Molecular Fluorophores.

Carbon dots (CDs) are an intriguing fluorescent material; however, due to a plethora of synthesis techniques and precursor materials, there is still significant debate on their structure and the origin of their optical properties. The two most prevalent mechanisms to explain them are based on polycyclic aromatic hydrocarbon domains and small molecular fluorophores, for instance, citrazinic acid. Yet, how these form and whether they can exist simultaneously is still under study. To address this, we vary the hydrothermal synthesis time of CDs obtained from citric acid and ethylenediamine and show that in the initial phase molecular fluorophores, likely 2-pyridone derivatives, account for the blue luminescence of the dots. However, over time, while the overall size of the CDs does not change, aromatic domains form and grow, resulting in a second, faster decay channel at similar wavelengths and also creating additional lower energetic states. Electrophoresis provides further evidence that the ensemble of CDs consists of several subsets with different internal structure and surface charge. The understanding of the formation mechanism enables a control of the chemical origin of these emitters and the ensuing optical properties of the CDs through synthetic means.

Development of a Practical Synthesis of a Peripherally Selective Noradrenaline Reuptake Inhibitor Possessing a Chiral 6,7-trans-Disubstituted-1,4-oxazepane as a Scaffold

A practical synthesis of a peripherally selective noradrenaline reuptake inhibitor that has a chiral 6,7-trans-disubstituted-1,4-oxazepane as a new class of scaffold is described. The amino alcohol possessing the desired stereochemistry was obtained with excellent dr and ee, starting from a commercially available aldehyde via a Morita–Baylis–Hillman reaction, Michael addition, isolation as maleic acid salt, reduction, and diastereomeric salt formation with (+)-10-camphorsulfonic acid. The desired single stereoisomer obtained at an early stage of the synthesis was used for seven-membered ring formation in fully telescoped processes, providing the chiral 6,7-trans-disubstituted-1,4-oxazepane efficiently. In addition to controls of dr and ee of the chiral 1,4-oxazepane, and control of N,O-selectivity in SN2 reaction of the intermediate mesylate with a pyridone derivative, finding appropriate intermediates that were amenable to isolation and upgrade of purity enabled a practical chiral HPLC separation-free, c...

Synthesis and Antimicrobial Activity Evaluation of Some Novel Hydrazone, Pyrazolone, Chromenone, 2-Pyridone and 2-Pyrone Derivatives

A cyanoacetohydrazide derivative underwent a series of reactions with different nucleophilic reagents, such as hydrazine hydrate, p-chlorobenzaldehyde and salicylaldehyde, to give the condensation products. In addition, an arylidene malononitrile was reacted with different nitrogen nucleophiles, such as hydrazine hydrate, thiocarbohydrazide and cyanoacetohydrazide, to afford the hydrazine, hydrazone and pyridin-2-one derivatives, respectively. Furthermore, a pyridin-2-one derivative was reacted with different carbon electrophiles, such as carbon disulfide, p-chlorobenzaldehyde and acetic anhydride. The antimicrobial activities of some of the compounds were examined.

Synthesis and Evaluation of Antioxidant Activity of Some New Heterocyclic Compounds Bearing the Benzo[B]Furan Moiety

New compounds were synthesized by the reaction of 3-acetyl-5- methoxy-2-methylbenzofuran (1) with cyanoacetylhydrazine which afforded the hydrazide hydrazone derivative 2. Compound 2 underwent a series of heterocyclization reactions to give the new pyrazole, isoxazole, cyclopentanothiophene, thiazole, triazole, 2H-chromene and pyridone derivatives (3-13). The elemental and spectral data (IR, 1H NMR and MS) characterized their structures. Screening for some selected compounds was carried for their potential antioxidant activities using ABTS. Among the tested samples compounds 9, 11, 5 and 10 exhibited promising activity.

A Green Approach to the Production of 2-pyridone Derivatives Promoted by Infrared Irradiation

An alternative is presented for promoting a reaction with infrared irradiation to obtain different 4-aryl-3-cyano-5-ethoxycarbonyl-6-methyl-2-pyridone derivatives 9a-k. The process was carried out with a green approach from the corresponding 4H-pyrans, using mild reaction conditions and infrared irradiation as the energy source. In the first stage, the reaction produced 1,2,3,4-tetrahydropyridin-2-one derivatives 8a-k, followed by an oxidative step to afford the target molecules in good yields. The structure of products 9a-k was confirmed by FT-IR, 1H NMR and 13C NMR spectroscopic techniques and X-ray diffraction. It was found that the efficiency of the reaction depends on the catalyst and the solvent, as well as on the aldehyde substituents.

Synthesis and antiviral activity of 1,2,3-triazole glycosides based substituted pyridine via click cycloaddition

Novel conjugates of substituted pyridine and carbohydrate moieties linked by 1,2,3-triazoles were synthesized. The propargyl group was introduced by O-propargylation of pyridone derivatives. Attachment of carbohydrate molecules to the substituted pyridine core was performed by Cu-catalyzed cycloaddition of propargyl sugars with azidoethoxypyridine derivative or azido-sugars with substituted (propargyl)oxypyridines which afforded the corresponding 1,2,3-triazoles in high yields. Antiviral activity of synthesized compounds was studied against H5N1 influenza virus and triazolyl glycoside 7 demonstrated high activity in addition to its low toxicity. The effect of attachment of glycosyl triazole moieties to pyridinyl system was studied, in SAR correlation, which has been found to enhance antiviral activity.

Synthesis of Pyridone Derivatives from 7‐Hydroxy‐7‐polyfluoroalkylhexahydroimidazo[1,2‐a]pyridin‐5‐ones

The synthesis of 1‐(2‐aminoethyl)‐6‐alkyl‐4‐polyfluoroalkylpyridin‐2‐ones based on the acidic cleavage of 7‐hydroxy‐7‐polyfluoroalkylhexahydroimidazo[1,2‐a]pyridin‐5‐ones is reported. Depending on the reaction conditions, the pyridones can be obtained as bases, salts, acetamides, or the products of intramolecular cyclization, dihydroimidazopyridines. High tuberculostatic activity was observed for some of the synthesized compounds.

A pyridone derivative activates SERCA2a by attenuating the inhibitory effect of phospholamban

The cardiac sarco/endoplasmic reticulum Ca2+-dependent ATPase 2a (SERCA2a) plays a central role in Ca2+ handling within cardiomyocytes and is negatively regulated by phospholamban (PLN), a sarcoplasmic reticulum (SR) membrane protein. The activation of SERCA2a, which has been reported to improve cardiac dysfunction in heart failure, is a potential therapeutic approach for heart failure. Therefore, we developed a novel small molecule, compound A and characterized it both in vitro and in vivo. Compound A activated the Ca2+-dependent ATPase activity of cardiac SR vesicles but not that of skeletal muscle SR vesicles that lack PLN. The surface plasmon resonance assay revealed a direct interaction between compound A and PLN, suggesting that the binding of compound A to PLN attenuates its inhibition of SERCA2a, resulting in SERCA2a activation. This was substantiated by inhibition of the compound A-mediated increase in Ca2+ levels within the SR of HL-1 cells by thapsigargin, a SERCA inhibitor. Compound A also increased the Ca2+ transients and contraction and relaxation of isolated adult rat cardiomyocytes. In isolated perfused rat hearts, the compound A enhanced systolic and diastolic functions. Further, an infusion of compound A (30mg/kg, i.v. bolus followed by 2mg/kg/min, i.v. infusion) significantly enhanced the diastolic function in anesthetized normal rats. These results indicate that compound A is a novel SERCA2a activator, which attenuates PLN inhibition and enhances the systolic and diastolic functions of the heart in vitro and in vivo. Therefore, compound A might be a novel therapeutic lead for heart failure.

Synthesis and antimicrobial evaluation of some novel dithiolane, thiophene, coumarin, and 2-pyridone derivatives

ABSTRACTNovel 2-cyano-N-[1-(naphtha-2-yl)ethylidene] acetohydrazide 1 was utilized as key intermediate for the synthesis of some new dithiolane, thiophene, coumarin, 2-pyridone, and other related products containing a hydrazide moiety. Newly synthesized compounds were characterized by elemental analyses and spectral data (IR, 1H NMR and mass spectra). The antimicrobial activity of the synthesized compounds was evaluated.

Discovery of 1-(4-((3-(4-methylpiperazin-1-yl)propyl)amino)benzyl)-5-(trifluoromethyl)pyridin-2(1H)-one, an orally active multi-target agent for the treatment of diabetic nephropathy

Oxidative stress, inflammation and fibrosis can cause irreversible damage on cell structure and function of kidney and are key pathological factors in Diabetic Nephropathy (DN). Therefore, multi-target agents are urgently need for the clinical treatment of DN. Using Pirfenidone as a lead compound and based on the previous research, two novel series (5-trifluoromethyl)-2(1H)-pyridone analogs were designed and synthesized. SAR of (5-trifluoromethyl)-2(1H)-pyridone derivatives containing nitrogen heterocyclic ring have been established for in vitro potency. In addition, compound 8, a novel agent that act on multiple targets of anti-DN with IC50 of 90μM in NIH3T3 cell lines, t1/2 of 4.89±1.33h in male rats and LD50>2000mg/kg in mice, has been advanced to preclinical studies as an oral treatment for DN.

SYNTHETIC ROUTES AND NATURAL SOURCES OF 2-PYRIDONE DERIVATIVES AND THEIR PHARMACOLOGICAL ACTIVITY

Objective: 2-pyridone is a well-known heterocyclic ring having significant biological and medical application. The molecular structures and various activities of 2-pyridone derivatives as well as their syntheses and natural occurrence are analyzed and reviewed, and their reactivity toward various nucleophiles is discussed.Methods: 2-pyridone derivatives, first naturally obtained and described as early as before the 19th century, have been attracting increasing attention in view of their high reactivity as building blocks for the preparation of compounds of various classes due to their selective transformations with different reagents. Much information describing the natural occurrence, synthesis and the significant biological activity of 2-pyridone compounds are scattered throughout the literature. There are short chapters dealing with the synthesis and activity of 2-pyridone derivatives.Results: After compiling the above material, the abundance of certain heterocyclic ring and nature of typical chemical transformations applied in current drug synthesis. It is likely this results from the abundance of these heterocycles in natural products such as alkaloids and various synthetic derivatives revealing different biological activity. This might suggest a classical approach to drug design where substrate analogs gain inspiration from existing natural ligands.Conclusions: The data considered in this review clearly demonstrate the high synthetic potential of 2-pyridone derivatives. Many biologically active heterocyclic compounds have been obtained based on this heterocyclic ring. This suggests that 2-pyridone can be used in the design of novel highly effective pharmaceuticals with a broad spectrum of bioresponses.

Rapid synthesis of a hyperfluorescence 2-pyridone derivative as a fluorescent molecular sensor for picric acid

In this article, a hyperfluorescence 2-pyridone derivative (D-TPCA) has been synthesized within 5min by the microwave-assistant heat treatment of the aqueous mixture of citric acid and 2-aminoethanethiol hydrochloride. The as-prepared D-TPCA exhibited good aqueous solubility and excellent fluorescent property with a quantum yield of 89.9%. Because the fluorescence of D-TPCA could be effectively quenched by picric acid (PA), D-TPCA could be served as a “turn-off” fluorescence sensor for PA in aqueous solution. The proposed sensing method permitted a selective and sensitive detection of PA in a linear range of 0–45μM with a detection limit of 56.0nM. The determination results of PA in real water samples with a recovery range of 95.4–107.3% confirmed a good analytical performance of this sensor. In addition, the possible sensing mechanism has been discussed in detail.

Design, synthesis and primary biological evaluation of the novel 2-pyridone derivatives as potent non-nucleoside HBV inhibitors

In continuation of our efforts toward the discovery of potent non-nucleoside hepatitis B virus (HBV) inhibitors with novel structures, we have employed bioisosterism and hybrid pharmacophore-based strategy to explore the chemically diverse space of bioactive compounds. Cytotoxicity, anti-HBV antigen secretion activities and anti-HBV DNA replication activity were assayed with cell counting kit-8 (CCK-8), enzyme linked immunosorbent assay (ELISA) and a real-time PCR, respectively. Some of the new compounds were able to inhibit the replication of HBV DNA activity in the low micromolar range. In particular, compound 8u displayed the most potent activity against the replication of HBV DNA with IC50 value of 3.4 μM. The preliminary structure-activity relationship (SAR) of these new compounds was investigated, which may help designing more potent molecules.

On the Molecular Origin of Photoluminescence of Nonblinking Carbon Dot

The molecular origin of the photoluminescence (PL) of carbon dots (CDs) is not fully understood. In this article it is shown that CDs are composed of aggregated 2-pyridone derivatives employing π–π stacking and H-bonding, etc. The PL quantum yield of this CD is quite high in aqueous medium (∼75%). Unlike literature reports the PL emission maximum of this CD is excitation wavelength independent, and PL decay follows a single-exponential decay equation. These CDs have a long PL lifetime (from ∼10 to 15 ns), so that solvation is complete before emission. The extent of trap states could be reduced quite significantly. A high PLQY and long and single-exponential PL lifetime and it’s polarity dependence would make this CD a suitable probe for FRET and FLIM. It could be shown that unlike literature reports this CD as a single particle does not blink. Unlike literature reports where CDs are bleached within a few seconds these CDs at the single-particle level are alive for about a few minutes. All these aggregatio...