Journal of Heterocyclic Chemistry最新文献

{"title":"Amberlyst A21-Catalyzed Green Synthesis of Novel Azo-Fused Benzo[d]Imidazolyl Phenyl Methanones: Molecular Docking, DFT Insights and α-Glucosidase Inhibitory Activity","authors":"Udhayakumar Peroli,&nbsp;Ponmalai Kavina,&nbsp;Venkatesan Kavishree,&nbsp;Ramasamy Shankar,&nbsp;Pazhani Beena Shamini,&nbsp;Appaswami Lalitha","doi":"10.1002/jhet.70238","DOIUrl":"https://doi.org/10.1002/jhet.70238","url":null,"abstract":"<div>\u0000 \u0000 <p>A green and sustainable synthetic protocol was established for the synthesis of novel azo-fused benzo[d]imidazolylphenyl methanone derivatives using arylazo salicylaldehydes and 3,4-diaminobenzophenone in the presence of Amberlyst A21 as a recyclable heterogeneous base catalyst under mild reaction conditions. The developed methodology afforded the desired products in good to excellent yields with operational simplicity and catalyst reusability. Employing ethanol as an eco-friendly solvent and a recyclable, metal-free polymer-supported catalyst reinforces the environmentally benign and sustainable nature of the methodology. Structure elucidation of the synthesized compounds was accomplished using FT-IR, ¹H NMR, ¹³C NMR, and ESI-MS analyses. In silico molecular docking investigations were conducted against the human lysosomal acid α-glucosidase enzyme (PDB ID: 5NN8) to explore the binding modes of the synthesized compounds. All the compounds exhibited excellent binding affinities from −9.1 to −10.4 kcal/mol and various biomolecular interactions with the target. Molecular dynamics was performed for the complex 5NN8-3k at 100 ns. DFT calculations at the B3LYP/6-311G* (d,p) level were performed to evaluate the electronic properties of compounds 3(a–o). The selected compound 3k was further evaluated through in silico ADMET analysis to predict its pharmacokinetic and toxicity properties. The synthesized compound 3k was further assessed for its antidiabetic potential through an in vitro α-glucosidase inhibition study, exhibiting significant inhibitory activity with an IC₅₀ value of 47.487 μg/mL in comparison to the standard acarbose (IC₅₀ = 29.287 μg/mL). The computational and experimental findings collectively suggest that azo-fused benzo[d]imidazol-5-yl)(phenyl)methanone scaffolds represent promising candidates for further development of potential α-glucosidase inhibitors through a green and sustainable synthetic approach.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"63 11","pages":"1644-1665"},"PeriodicalIF":2.9,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149312066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"One-Pot Green Microwave Synthesis and Computational Study of 1,4-Benzodiazepine Derivatives: Docking, ADME-Tox, Dynamics, and DFT","authors":"Dhaval B. Patel,&nbsp;Siddharth S. Patel,&nbsp;Hitesh D. Patel","doi":"10.1002/jhet.70244","DOIUrl":"https://doi.org/10.1002/jhet.70244","url":null,"abstract":"<div>\u0000 \u0000 <p>A one-pot, green, and microwave-assisted method has been efficiently developed for the synthesis of 1,4-benzodiazepine derivatives via the reaction of various aldehydes, ethyl acetoacetate, and o-phenylenediamine in the presence of Bi(NO₃)₃·5H₂O as an effective catalyst. Biological activity of synthesized compounds was tested against antibacterial, antifungal, and antimalarial strains. Compound <b>4b</b> showed excellent activity 62.5 and 25 μg/mL against <i>Escherichia coli</i> and <i>Candida albicans</i>, respectively. Compound <b>4f</b> showed good activity 100 μg/mL against <i>Pseudomonas aeruginosa</i>. Also Compounds 4d and 4 g shown significant activity, with IC₅₀ values of 0.19 μg/mL and 0.17 μg/mL, respectively, in comparison with the reference drug quinine. Furthermore, computational investigations were performed to support the biological findings. Molecular docking studies were carried out to evaluate the binding interactions of the synthesized compounds with the target protein (PDB ID: 3DGA), followed by molecular dynamics simulations to assess the stability of the protein–ligand complexes. ADME-Tox analyses were conducted to predict the pharmacokinetic and toxicity profiles of the compounds. In addition, quantum chemical calculations, including frontier molecular orbital (FMO) analysis, were performed. Electronic descriptors such as HOMO energy (E_HOMO), LUMO energy (E_LUMO), energy gap (Δ<i>E</i>), dipole moment (<i>μ</i>), electronegativity (<i>χ</i>), and global hardness (<i>η</i>) were calculated to evaluate the electronic properties, chemical reactivity, and potential bioactivity of the synthesized molecules.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"63 11","pages":"1724-1736"},"PeriodicalIF":2.9,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149312265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gold(I)-Catalyzed Annulation of Pyridines Containing Alkyne: Synthesis of N-Alkenyl Pyridonyl Azides via Rearrangement","authors":"Ali Osman Karatavuk","doi":"10.1002/jhet.70240","DOIUrl":"https://doi.org/10.1002/jhet.70240","url":null,"abstract":"<p>A novel strategy, involving the preparation of gold-catalyzed cyclization salts and the rearrangement of these salts in the presence of azides, has been developed for the synthesis of <i>N</i>-alkenyl pyridonyl azides. The method was proven to tolerate a large number of groups and to produce moderate to excellent yields of transformation in reactions involving chains of different lengths. The usage of powerful electron-withdrawing groups, such as the nitro group, determined the method's limitations. The five-membered ring was shown to be easier to create in the first stage when rings of various sizes were formed with trifluoromethyl groups, whereas the six-membered ring was more reactive in the second stage.</p>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"63 11","pages":"1637-1643"},"PeriodicalIF":2.9,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jhet.70240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149312067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of Novel Glutarimide Derivatives via the Interaction of α-Methyleneglutarimide With Chlorohydrazones","authors":"Mikhail Konoplev,&nbsp;Alexander Bunev,&nbsp;Grigory Kantin,&nbsp;Dmitry Dar'in,&nbsp;Alexander Sapegin","doi":"10.1002/jhet.70245","DOIUrl":"https://doi.org/10.1002/jhet.70245","url":null,"abstract":"<div>\u0000 \u0000 <p>A convenient approach to the generation of two novel chemotypes of potential CRBN ligands via the interaction of α-methyleneglutarimide with chlorohydrazone derivatives is described. The introduction of <i>N</i>-aryl substituted chlorohydrazones into the reaction leads to the formation of 1,2,7-triazaspiro[4.5]dec-2-ene-6,8-diones with yields of 16%–76%. Conducting the synthesis with the participation of <i>N</i>-<i>Boc</i> chlorohydrazones yields 3-((2-oxo-1,3,4-oxadiazol-3(2<i>H</i>)-yl)methyl)piperidine-2,6-diones as products in 31%–65% yields. The synthesized compounds exhibit moderate cytotoxicity in in vitro assays against myeloma (MM1.S) and normal (PBMS) cell lines, supporting their safety profile as potential CRBN ligands.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"63 11","pages":"1710-1723"},"PeriodicalIF":2.9,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149312264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Insights Into the 1,3-Dipolar Cycloaddition of Diethyl Phosphorylazidate With Isothiocyanates: A DFT Approach","authors":"Outaf Fliss,&nbsp;Aicha Zeine,&nbsp;M. Abederrahmene Sanhoury,&nbsp;Nejib Mekni","doi":"10.1002/jhet.70242","DOIUrl":"https://doi.org/10.1002/jhet.70242","url":null,"abstract":"<div>\u0000 \u0000 <p>The synthesis of novel 1-diethylphosphoryl-4-substituted tetrazoline-5-thiones was achieved in good yields via the 1,3-dipolar cycloaddition of diethylphosphoryl azidate with phenyl- and allyl isothiocyanates. Density functional theory (DFT) calculations were carried out to determine the most stable conformations of resulting tetrazoline-5-thiones. The study of the reaction mechanism, based on the evolution of the intrinsic reaction coordinate (IRC) calculation parameters (energy, bond lengths, angles, and dihedral angles) through the different reaction states (SM, TS, Product, and optimized product) and using the Molecular Electron Density Theory (MEDT) method at the SMD-M062X-D3/6-311G(d,p) level of theory, indicates that the reaction may follow an asynchronous, concerted, or two-step mechanism depending on the specific starting isothiocyanate used conformer.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"63 11","pages":"1752-1769"},"PeriodicalIF":2.9,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149312780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment on Prominent Synthetic Approaches for the Cholesterol Absorption Inhibitor Ezetimibe and Their Process Impurities: A Review","authors":"Aluru Rammohan,&nbsp;Grigory V. Zyryanov","doi":"10.1002/jhet.70237","DOIUrl":"https://doi.org/10.1002/jhet.70237","url":null,"abstract":"<div>\u0000 \u0000 <p>Hyperlipidemia, a major global health concern and a primary cause of high mortality, is exacerbated by elevated cholesterol and triglyceride profiles. Thus, it is possible to optimally control lipid levels and prevention of the progression of hyperlipidemia and associated diseases through drug treatments, emerging therapies, and lifestyle modifications. Among antihyperlipidemia therapeutic drugs, the cholesterol absorption inhibitor (CAI) ezetimibe is an important lipid-lowering agent that actively reduces dietary and biliary cholesterol absorption. Accordingly, the present review summarizes the prominent synthetic approaches of ezetimibe and their synthetic analogues, as well as their process impurities. In addition, the inclusive study highlights the expansions of API impurities and their optimization for scale-up techniques for ezetimibe drug. Further, this study also collectively abridges the research and developments of ezetimibe analogues such as glucuronide fluorescent derivatives, sulfonyl-glucuronides, amide-, and sulfonamide derivatives for enriched antihyperlipidemia drug developments. Therefore, this review précises the important synthetic developments of ezetimibe and its derivatives that could be assisted as a template for the further expansion of antihyperlipidemia and azetidinone based drug leads.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"63 11","pages":"1737-1751"},"PeriodicalIF":2.9,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149312263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficient and General Synthesis of 2-Substituted 2-Methyl 2H-Chromenes Under Lewis Acid-Catalyzed Conditions","authors":"Aedula Vishnu V. Reddy,&nbsp;Gheya Bharathi Tammu,&nbsp;Debendra K. Mohapatra","doi":"10.1002/jhet.70243","DOIUrl":"https://doi.org/10.1002/jhet.70243","url":null,"abstract":"<div>\u0000 \u0000 <p>An efficient and operationally straightforward approach has been developed for the synthesis of 2-allyl-2-methyl-2<i>H</i>-chromenes under Lewis acid-mediated conditions. The reaction proceeds via initial isomerization of the (<i>E</i>)-double bond in the enone substrate, followed by intramolecular cyclization and nucleophilic trapping. This cascade sequence offers several notable advantages, including mild reaction conditions, sequential isomerization with concurrent formation of both C–O and C–C bonds in a single step, the use of readily accessible reagents, broad substrate tolerance toward electron-donating and halo substituents, and good to excellent isolated yields.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"63 11","pages":"1666-1677"},"PeriodicalIF":2.9,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149311913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Water and Fe Based Nanoparticle-Promoted Synthesis of Isatin Frameworks: A Green and Synergistic Methodology","authors":"Bhavana Sharma,&nbsp;Shubham Sharma,&nbsp;Prabal Pratap Singh,&nbsp;Tanishika Kaushik","doi":"10.1002/jhet.70241","DOIUrl":"https://doi.org/10.1002/jhet.70241","url":null,"abstract":"<div>\u0000 \u0000 <p>Over the past years, green chemistry principles and criteria have advanced the field and led to the development of more sustainable options in synthetic organic chemistry. In this context, the renewable catalytic system and solvent selection has become the major parameters. This review is a critical survey of the recent developments in the synthesis of isatin frameworks, accomplished using synergism between water as a benign reaction medium and the iron based nanoparticles as a heterogeneous catalyst which highlights environmentally friendly and sustainable chemistry. The reported studies demonstrate that the water-based reaction media with Fe-based nanoparticles have generally shown high product yields, shorter reaction times, better reusability of the catalysts, and low environmental impact in comparison to the conventional synthetic procedures. Moreover, the reported approaches are also well compatible with diverse substrates and have great potential in the sustainable and scalable synthesis of isatin frameworks applicable in the field of pharmaceuticals and fine chemicals. This work is the first to show the synergistic effect of magnetic nanocatalyst and aqueous medium toward the preparation of biologically important isatin-based molecular hybrids.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"63 11","pages":"1678-1709"},"PeriodicalIF":2.9,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149312357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temperature-Controlled Cyclization of Anthranilic Acids to 2-Thioxoquinazolin-4-One or Thiazoloquinazolinone Derivatives Under Microwave Irradiation","authors":"Julie Jaouen,&nbsp;Christian Bailly,&nbsp;Natacha Carta,&nbsp;Xavier Thuru,&nbsp;Jean-François Goossens,&nbsp;Laurence Goossens","doi":"10.1002/jhet.70229","DOIUrl":"https://doi.org/10.1002/jhet.70229","url":null,"abstract":"<div>\u0000 \u0000 <p>Investigation of the microwave-assisted condensation of anthranilic acid derivatives with ethylpiperidine isothiocyanates into 2-thioxoquinazolin-4-ones revealed an intramolecular cyclization into 2,3-dihydro-5<i>H</i>-thiazolo[2,3-<i>b</i>]quinazolinones. The study of reaction parameters demonstrated that temperature is a key factor controlling this transformation, while anthranilic acid substituents further modulate the reaction outcome. Here we report the promotion of the intramolecular cyclization to thiazoloquinazoline at high temperatures (200°C), whereas lower temperature (125°C) selectively favors the formation of 2-thioxoquinazolin-4-one in good yield. These findings provide refined conditions for the synthesis of 2-thioxoquinazolin-4-one derivatives and expand the way to synthesize 2,3-dihydro-5<i>H</i>-thiazolo[2,3-<i>b</i>]quinazolinone derivatives of potential medicinal interest.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"63 10","pages":"1565-1572"},"PeriodicalIF":2.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149100018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of Substituted 6-Aminothieno[2,3-b]Pyridine-5-Carbonitriles by Multicomponent Condensation of 2-Aminothiophenes With Aldehydes and Malononitrile","authors":"Ilya A. Komkov,&nbsp;Boris V. Lichitsky","doi":"10.1002/jhet.70222","DOIUrl":"https://doi.org/10.1002/jhet.70222","url":null,"abstract":"<div>\u0000 \u0000 <p>For the first time, the multicomponent reaction of labile 2-aminothiophenes with aldehydes and malononitrile was investigated. We have shown that the considered process leads to the formation of thieno[2,3-<i>b</i>]pyridine derivatives containing cyano- and amino groups. Sodium salts of 2-aminothiophene-3-carboxylic acids were utilized as straightforward precursors for the generation of unstable 2-aminothiophenes in situ. Based on the presented multicomponent condensation, the general method for the synthesis of final 6-aminothieno[2,3-<i>b</i>]pyridine-5-carbonitriles was designed. The elaborated procedure allowed us to obtain a large array of target products with yields up to 68%. Advantages of the developed approach are easily available starting materials, atom economy, and convenient isolation of prepared compounds without chromatographic purification. The structure of one representative of the synthesized thieno[2,3-<i>b</i>]pyridines was confirmed by X-ray analysis.</p>\u0000 </div>","PeriodicalId":194,"journal":{"name":"Journal of Heterocyclic Chemistry","volume":"63 10","pages":"1462-1475"},"PeriodicalIF":2.9,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149099625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}