Journal of Heterocyclic Chemistry最新文献

A straightforward, safe, and effective visible light-mediated metal-free organophotocatalyzed process has been developed to synthesize potentially bioactive substituted benzofuran scaffolds. This synthetic protocol uses visible light-mediated acridinium as a photocatalyst to catalyze the cycloaddition reaction between substituted phenol and diphenyl acetylene following photoredox conditions at room temperature. Gentle reaction conditions, good to exceptional results, high atom economy, environmentally benign procedures, apparent reaction conditions, and the suitability for large-scale synthesis are a few of the specific features of this current synthetic protocol.

A straightforward, safe, and effective visible light-mediated metal-free organophotocatalyzed process has been developed to synthesize potentially bioactive substituted benzofuran scaffolds. This synthetic protocol uses visible light-mediated acridinium as a photocatalyst to catalyze the cycloaddition reaction between substituted phenol and diphenyl acetylene following photoredox conditions at room temperature. Gentle reaction conditions, good to exceptional results, high atom economy, environmentally benign procedures, apparent reaction conditions, and the suitability for large-scale synthesis are a few of the specific features of this current synthetic protocol.

In order to develop pyridone compounds with good antioxidant ability and bacteriostatic activity, the compounds 3-(benzyloxy)-2-ethyl-1-propylpyridin-4(1H)-one (5a) to 3-(benzyloxy)-2-ethyl-1-(4-methylbenzyl)pyridin-4(1H)-one (5e) were obtained through two steps reaction. The structures were confirmed using nuclear magnetic resonance (¹H-NMR, ¹³C-NMR), Fourier transform infrared spectrometer (FT-IR), and high resolution mass spectrometry (HRMS). The antioxidant ability of compounds 5a–5e was identified by using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and hydroxyl radicals (·OH) methods. Turbidimeter method and mycelial growth rate method were used for the determination of in vitro bacteriostatic activity of compounds 5a–5e against gram-negative bacteria [ Escherichia coli ( E. coli ), Pseudomonas aeruginosa ( P. aeruginosa )], gram-positive bacteria [ Bacillus subtilis ( B. subtilis ), Staphylococcus aureus ( S. aureus )], and fungi [Botrytis cinerea ( B. cinerea )]. The antioxidant results showed that at the concentration of 2 mg/mL, compounds 3-(benzyloxy)-2-ethyl-1-(furan-2-ylmethyl)pyridin-4(1H)-one (5c) and 5e exhibited stronger free radical scavenging ability than ethyl maltol. The bacteriostatic activity results showed that compounds 5a and 5e showed good bacteriostatic activities against S. aureus and B. cinerea . Molecular docking results showed that compounds 5a and 5e inhibit the activity of pyruvate dehydrogenase, thereby achieving bacteriostatic effect. This study not only synthesized novel heterocyclic compounds, but also provided new ideas and references for the development and selection of bacteriostatic agents.

Coumarin (2H-chromen-2-one) and its derivatives represent a significant class of organic compounds, known for their natural occurrence and wide range of pharmaceutical applications. The coumarin scaffold is highly versatile, enabling modifications at various positions on its core structure, often leading to enhanced biological activities, such as antimicrobial, antioxidant, anti-inflammatory, anticoagulant, antitumor, and enzyme inhibition properties. These modifications not only improve therapeutic potential but also facilitate selective interactions with a variety of biological targets, making coumarin derivatives promising candidates in drug discovery for cancer, neurodegenerative diseases, and metabolic disorders. This review summarizes the various synthetic methods for producing coumarin derivatives, emphasizing the use of different starting materials such as aldehydes, phenols, ketones, carboxylic acids, and reaction conditions to achieve the desired structural modifications. It also highlights the biological importance of these compounds, focusing on their enhanced activities due to structural modifications and their potential in therapeutic applications.

The discovery of therapeutic agents is important for cancer treatment. Although dozens of agents have been used in cancer treatments, cancer continues to be a serious disease with a high mortality rate. There is an urgent need for the discovery of new anticancer agents, especially for the long-term treatment of prostate cancer. Thanks to the expansion of cancer-related data, we now can synthesize new therapeutic agents using biological methods. Carboxamide derivatives (5a–r compounds) were synthesized as a potential anticancer agent. Cell proliferation assays showed that they had antiproliferative activity against the human prostate cancer cell line PC3, particularly at the 25 μM dose. In summary, our findings revealed that 5g–l and 5m–r groups are effective agents against the prostate cancer cell line. In conclusion, Gaussian calculations were carried out in order to investigate carboxamide derivatives (5a–r compounds) at the B3LYP, HF, and M062X levels, using the 6–31++g(d,p) basis set. Molecular docking calculations were carried out on a variety of proteins, including the protein that is associated with prostate cancer (PDB ID: 3RUK and 3A99). Calculations using the ADME/T method are carried out in order to investigate the potential effects and reactions of these medicines on human metabolism.

In this study, we synthesized a series of aromatic carbothioamide derivatives bearing a benzimidazole scaffold. Subsequently, their thiadiazole and triazole analogs were prepared through intramolecular cyclization under acidic and basic conditions. Additionally, thiazolidinone derivatives were synthesized via cyclization in the presence of ethyl bromoacetate. The in vitro inhibitory activities of all synthesized compounds against urease and acetylcholinesterase (AChE) were evaluated. All compounds showed significant inhibitory effects, with IC₅₀ values ranging from 7.50 ± 0.20 to 9.05 ± 0.10 μg/mL against urease (standard: thiourea, 15.75 ± 0.15 μg/mL) and from 7.25 ± 0.15 to 9.35 ± 0.05 μg/mL against AChE (standard: galantamine, 20.75 ± 0.25 μg/mL). Among them, the triazole derivative 3b was identified as the most potent urease inhibitor (IC₅₀ = 7.50 ± 0.20 μg/mL). Notably, carbothioamide derivative 2c exhibited superior dual inhibitory activity, with IC₅₀ values of 7.25 ± 0.15 μg/mL for AChE and 7.80 ± 0.10 μg/mL for urease, making it a promising candidate for multi-target enzyme inhibition. Molecular docking studies further supported these findings by revealing strong and stable interactions of 2c within the active sites of both enzymes, which correlates well with its experimental potency. These results highlight compound 2c as a compelling lead structure for the development of dual-target therapeutic agents, combining significant experimental activity with theoretical validation.

The current work describes the synthesis and comprehensive characterization of a newly studied 2-oxindole derivative, designed through a three-step process involving condensation, alkylation, and aminolysis reactions. The title compound was rigorously characterized using elemental analysis, ¹H and ¹³C-NMR spectroscopy, as well as single-crystal X-ray diffraction analysis revealing a stable spirocyclic structure. The X-ray experimental data revealed the formation of an extensive 3D intermolecular hydrogen bonding network involving mostly the hydrazine moieties and the carbonyl oxygen atoms. In parallel, quantum chemical calculations (DFT) were performed at the B3LYP/6-31G(d,p) theoretical level to elucidate the compound's electronic properties. The findings indicate that replacing the carbonyl functional group with a dioxolane ring to form the spirocyclic structure increases the overall stability of the title compound and also shifts it to be more nucleophilic as evidenced by HOMO-LUMO energy gaps (ΔE = 4.59 eV) and global reactivity descriptors (such as electronegativity χ = 3.76 eV) for the title compound, compared to its structurally similar compound (ΔE = 3.16 eV and χ = 4.84 eV). Notably, the global descriptors demonstrate nucleophilic attack sites, aligning with experimental observations. The overall results highlight the compound's unique spiro architecture and provide insights into its reactivity for future applications in heterocyclic chemistry and drug design. Through integrated experimental and computational analysis, this study provides a validated platform for designing bioactive spirooxindole derivatives with tailored properties.

The importance of thiazines peaked during 1950s' owed mainly to their use as antipsychotics which is still continued to this day. This report summarizes different thiazine derivatives, their properties and focuses mainly on the syntheses of these compounds.

A series of glycoluril analogues (GA) have been synthesized by an improved Weiss–Cook condensation reaction. The structure of GA has been determined by single crystal X-ray diffraction technique, and the results show that there is only one enantiomer or diastereomer in these crystals. Based on the structural characteristics, this paper speculates on the possible reaction mechanism and tries to explain that such a one-step reaction is completely reasonable to generate only one enantiomer or diastereomer. Therefore, this method provides a simple route for the synthesis of chiral GA. Most importantly, this work also provides a chiral basic structural unit of cucurbituril or unclosed cucurbituril and lays a material foundation for the synthesis of novel unclosed cucurbituril or cucurbit[n]urils.

A novel series of biologically active aryl-pyrazin-2-yl-N, N-dimethyl piperidine amines and sulfonyl-pyridine-3-yl-pyrazinamine derivatives (3/5a-e) was synthesized and confirmed through ¹H NMR, ¹³C NMR, and mass spectrometry. All synthesized compounds were evaluated for their antibacterial activity against pathogenic microorganisms. Among them, compound 3b demonstrated the most potent antibacterial activity, particularly against Staphylococcus aureus and Escherichia coli . Furthermore, compound 3b was screened for anticancer activity against the A549 lung cancer cell line, showing promising cytotoxicity with an IC₅₀ value of 40 μg/mL. Structure–activity relationship (SAR) studies indicated that electron-donating groups significantly enhanced antibacterial activity, while electron-withdrawing groups led to a reduction in activity, and halogen substituents showed moderate antibacterial activity.