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Synthesis, Properties and Application of Five- and Six-Membered Heterocycles

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Organic Chemistry".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 2518

Special Issue Editors


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Guest Editor
Department of Chemistry and Industrial Chemistry (DCCI), University of Genova, Via Dodecaneso 31, 16146 Genova, Italy
Interests: heterocyclic compound; cyclization; ring opening reaction; carbazole; medicinal chemistry; michael addition

E-Mail Website
Guest Editor
Department of Chemistry and Industrial Chemistry (DCCI), University of Genova, Via Dodecaneso 31, 16146 Genova, Italy
Interests: heteroaromatic synthesis; organometallic nanohybrids; nitroderivatives; ring-opening and ring-closing reactions; computational chemistry; medicinal chemistry

Special Issue Information

Dear Colleagues, 

The rational design, efficient synthesis, and comprehensive characterization of five- and six-membered heterocyclic compounds represent essential components of modern organic and medicinal chemistry research. The enduring scientific interest in these privileged structural motifs arises from their widespread presence in bioactive natural products, pharmaceuticals, and advanced functional materials. These heterocyclic systems act as critical pharmacophores in drug discovery, demonstrating a broad spectrum of biological activities, including antimicrobial, anticancer, anti-inflammatory, and neurotropic effects. Additionally, five- and six-membered heterocycles exhibit remarkable utility in materials science, playing a significant role in organic electronics, photovoltaic devices, and luminescent materials. 

This Special Issue aims to present cutting-edge research highlighting the latest advancements in the chemistry of five- and six-membered heterocyclic compounds, either isolated or benzofused. We invite researchers to contribute original research articles, concise communications, and comprehensive reviews covering, but not limited to, the following key areas: 

  • Synthetic Methodologies: Development of novel and efficient synthetic strategies for five- and six-membered heterocycles, including transition-metal catalysis, multicomponent and cascade reactions, and green chemistry approaches. 
  • Structural Elucidation and Computational Studies: Advanced spectroscopic methods for characterization, complemented by computational studies such as density functional theory (DFT) calculations, molecular dynamics simulations, and quantum chemical analyses to explore reaction mechanisms and structure-property relationships. 
  • Pharmacological Investigations: Exploration of structure–activity relationships (SAR), biological evaluation, and innovative pharmacological applications. 
  • Materials Science Applications: Design, synthesis, and characterization of heterocycle-based materials for optoelectronic, photonic, and sensing applications. 
  • Comprehensive Reviews: analyses offering critical assessments of recent progress and future trends in the synthesis, characterization, and application of five- and six-membered heterocyclic compounds.

Dr. Lara Bianchi
Prof. Dr. Massimo Maccagno
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • heterocycle synthesis
  • transition-metal catalysis
  • multicomponent reactions
  • structural characterization
  • computational chemistry
  • pharmacological activity
  • functional materials
  • benzofused heterocycles

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Published Papers (3 papers)

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Research

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20 pages, 4974 KB  
Article
Regioselective Stepwise Synthesis of Unsymmetrical 1,2,5-Triarylpyrroles via Palladium-Catalyzed Decarboxylative Cross-Coupling and C–H Arylation
by Cindy Buonomano, Stephanie Patterson, Judith Sorel Ngou, Cynthia Messina, Sarah Taylor, François Bilodeau and Pat Forgione
Molecules 2026, 31(6), 986; https://doi.org/10.3390/molecules31060986 - 15 Mar 2026
Viewed by 560
Abstract
Pyrrole derivatives are natural organic molecules that are important to the pharmaceutical industry due to their occurrence in nature and their use in a wide range of medical applications. In general, non-symmetric, 1,2,5-triaryl-substituted pyrroles are prepared either by Paal–Knorr condensation or cycloaddition that [...] Read more.
Pyrrole derivatives are natural organic molecules that are important to the pharmaceutical industry due to their occurrence in nature and their use in a wide range of medical applications. In general, non-symmetric, 1,2,5-triaryl-substituted pyrroles are prepared either by Paal–Knorr condensation or cycloaddition that present synthetic challenges particularly if late-stage functionalization is required. The present study describes a modular approach to synthesizing 1,2,5-triarylpyrroles containing three different arene substituents. Using pyrrole ester building blocks, a sequence of decarboxylative cross-coupling and C–H arylation provides unsymmetrical 1,2,5-triarylpyrroles in a regioselective, stepwise manner; the scope and limitations of the sequence are disclosed. Full article
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Review

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36 pages, 18964 KB  
Review
Conjugated Nitroolefins as Twofold Electrophiles for the Assembly of Five-Membered Monoheterocycles via MIRC [3+2] Annulation: An Update on Synthetic and Mechanistic Aspects
by Lara Bianchi, Massimo Maccagno, Giovanni Petrillo and Cinzia Tavani
Molecules 2026, 31(5), 803; https://doi.org/10.3390/molecules31050803 - 27 Feb 2026
Viewed by 433
Abstract
Five-membered monoheterocycles, either isolated or embedded in more complex systems, are ubiquitous structural motifs in nature and hence privileged targets of synthetic chemistry. Among a plethora of methodologies used for their assembly, [3+2] annulation strategies keep attracting particular interest among chemists, partly because [...] Read more.
Five-membered monoheterocycles, either isolated or embedded in more complex systems, are ubiquitous structural motifs in nature and hence privileged targets of synthetic chemistry. Among a plethora of methodologies used for their assembly, [3+2] annulation strategies keep attracting particular interest among chemists, partly because of some significant characteristics from both the operative and the environmental viewpoints. Herein, the extensive use of conjugated nitroolefins as twofold electrophilic, two-carbon components of [3+2] MIRC (Michael-Initiated Ring Closure) annulations is reviewed as a practical and mechanistic update covering the last decade (2015–2025). Full article
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36 pages, 4306 KB  
Review
Recent Applications of Hydantoins in Drug Discovery: Updates (2019~Present)
by Jyoti Dnyaneshwar Palkhede, Eo-Jin Park, Om Darlami and Dongyun Shin
Molecules 2026, 31(5), 779; https://doi.org/10.3390/molecules31050779 - 26 Feb 2026
Cited by 1 | Viewed by 962
Abstract
Hydantoins, exemplified by the imidazolidine-2,4-dione core, are privileged scaffolds in medicinal chemistry due to their compact structure, versatile hydrogen-bonding capacity, ability to fine-tune physicochemical properties for drug-like molecules, and potential to engage a diverse array of biological targets. This review highlights major advances [...] Read more.
Hydantoins, exemplified by the imidazolidine-2,4-dione core, are privileged scaffolds in medicinal chemistry due to their compact structure, versatile hydrogen-bonding capacity, ability to fine-tune physicochemical properties for drug-like molecules, and potential to engage a diverse array of biological targets. This review highlights major advances in hydantoin-based drug discovery since 2019, emphasizing their evolving applications in oncology; neurology; infectious diseases; and cardiovascular, metabolic, and immune disorders. Recent studies demonstrate their success as kinase inhibitors, androgen receptor antagonists, and metalloprotease inhibitors, and emerging roles in modulating sterol isomerase, glycogen synthase kinase-3β, and ADAMTS family enzymes. Novel hybrid scaffolds—such as catechol–hydantoins, β-carboline–hydantoins, and spirocyclic thiohydantoins—have yielded potent and selective anticancer and antiviral leads. The discovery of BAY-9835 and GLPG1972 underscores the clinical potential of hydantoin-based metalloproteinase inhibitors in cardiovascular and osteoarthritic conditions. Furthermore, new antimicrobial, antimalarial, and antileishmanial derivatives illustrate the scaffold’s capacity to address multidrug resistance and neglected tropical diseases. Advances in computational design, stereochemical optimization, and hybridization strategies have expanded the structural and functional diversity of hydantoins, enhancing their target selectivity and pharmacokinetic profiles. Overall, hydantoins and their analogs remain at the forefront of small-molecule drug discovery, offering rich prospects for therapeutic innovation in diverse disease areas. Full article
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