Jul 2026· Mini-Reviews in Medical Chemistry· Vol 26· 0 citations
Medicine
TL;DR
This review provides a comprehensive and structured overview of modern synthetic strategies for sulfonamide construction, including classical sulfonyl chloride-amine coupling, metal-catalyzed synthesis of sulfonamides, microwave-assisted synthesis, and other advanced methodologies that enable efficient access to structurally diverse derivatives.
Abstract
Sulfonamides represent one of the most versatile scaffolds in medicinal chemistry. Since their introduction as the first synthetic antibacterial agents in the 1930s, the sulfonamide functional group (-SO₂NR₂) has enabled extensive structural diversification, leading to compounds with broad therapeutic applications. In recent years, sulfonamide derivatives have gained renewed attention in drug discovery due to their roles in antimicrobial, anticancer, antimalarial, antiviral, antiinflammatory, antidiabetic, and antioxidant therapies. This review provides a comprehensive and structured overview of modern synthetic strategies for sulfonamide construction, including classical sulfonyl chloride-amine coupling, metal-catalyzed synthesis of sulfonamides, microwave-assisted synthesis, and other advanced methodologies that enable efficient access to structurally diverse derivatives. In parallel, recent advances in the biological evaluation of sulfonamide analogues are discussed, with emphasis on emerging pharmacological targets and mechanistic insights, such as enzyme inhibition, metabolic interference, and receptor modulation. By correlating synthetic approaches with observed biological activities, this review highlights the structure-activity relationships that guide rational drug design. Current challenges, research gaps, and future perspectives for sulfonamide-based therapeutics are also outlined. Collectively, the adaptability of the sulfonamide scaffold, combined with continued advances in synthetic chemistry and biological screening, underscores its sustained importance in the development of next-generation therapeutic agents.
Sulfonamides belong to the most interesting classes of organic and bioactive compounds, historically introduced as the first widely used synthetic antibacterial agents. Currently, they still serve as versatile scaffolds across medicinal, coordination, and applied chemistry. Nowadays, the growing threat of antimicrobial resistance and the urgent need for improved therapeutic strategies are evident. Thus, sulfonamide derivatives have regained attention as adaptable platforms for designing compounds with broadened biological profiles, including their antimicrobial, anticancer, and enzyme-targeted activities. Moreover, sulfonamides have emerged as valuable ligands in coordination chemistry, offering diverse donor sets and binding modes that enable the design of metal-ion complexes with desired physicochemical properties and functions, including reactivity and biological behavior. It often selects and introduces multi-target mechanisms. Beyond biomedical relevance, sulfonamide-based coordination compounds are increasingly explored in catalytic applications, where ligand architecture and metal identity can be leveraged to control activity and selectivity. This review summarizes recent advances in sulfonamide chemistry and sulfonamide coordination compounds, emphasizing structure-property-function relationships, mechanistic trends, and emerging opportunities at the interface of disease treatment and catalysis.
M. Kowalik, Magdalena Stasiuk, Natalia Żukowska et al.· Journal of Inorganic Biochem...· 1 citation
Pyrazole and imidazole, two five‐membered aromatic diazole heterocycles containing two nitrogen atoms, have emerged as privileged scaffolds in medicinal chemistry due to their broad spectrum of biological activities and their presence in numerous clinically approved drugs. These structural motifs play key roles in the development of analgesic, anti‐inflammatory, antibacterial, antifungal, antitubercular, anti‐Alzheimer, and anticancer agents. The present review provides a comprehensive overview of the synthetic strategies employed for the preparation of diazole derivatives, encompassing both classical and modern approaches. Traditional methodologies, including the cyclocondensation of hydrazines or amidines as well as the Knorr and Debus reactions, are discussed alongside recent advances in catalytic and cycloaddition‐based synthetic techniques. Furthermore, the review highlights recent progress in the development of diazole‐based anti‐inflammatory agents, with particular emphasis on lead compounds exhibiting promising biological activity. In addition, recent in vitro and in vivo studies are critically summarized to provide insights into the therapeutic potential, mechanisms of action, and future prospects of pyrazole and imidazole derivatives as anti‐inflammatory drug candidates.
Ferhat Güneş, Beyzanur Aydın, M. Koca· ChemistrySelect· 0 citations
Oxazole derivatives are important heterocyclic scaffolds in medicinal chemistry due to
their broad biological activities. These five-membered aromatic rings containing oxygen and nitrogen
exhibit antimicrobial, antiviral, anticancer, anti-inflammatory, antifungal, and antitubercular
properties. Their favorable electronic features and structural rigidity enable strong and selective interactions
with diverse biological targets. Recent advances in synthetic methodologies, particularly
the van Leusen protocol using tosylmethylisocyanides (TosMICs), have enabled efficient and regioselective
oxazole construction. Additionally, magnetically recoverable catalysts offer sustainable
and recyclable approaches with improved yields and reduced environmental impact. These developments
have expanded the chemical space of oxazole-based compounds, facilitating the design of
drug candidates with enhanced pharmacokinetic and pharmacodynamic profiles. This review summarizes
recent synthetic strategies, pharmacological activities, structure–activity relationships, and
biosynthetic and mechanistic insights highlighting the significance of oxazole motifs in modern
drug discovery.
J. Sharma, Sushil Kumar· Mini-Reviews in Medical Chem...· 0 citations
β-Carboline derivatives are important nitrogen-containing heterocycles widely studied in medicinal chemistry because of their diverse biological activities and flexible chemical properties. This mini-review summarises recent progress reported from 2013 to 2025 in the synthesis and pharmacological evaluation of β-carboline-based compounds, with particular emphasis on their potential to address antimicrobial resistance. Key synthetic methods discussed include Pictet-Spengler cyclisation, oxidative aromatisation, and N-alkylation, which allow the preparation of structurally diverse derivatives such as hybrids, quaternary ammonium salts, and dimers. The review also highlights the broad therapeutic potential of these compounds, including antibacterial, antifungal, antimalarial, and antiviral activities. Structure-activity relationship studies show that modifications at positions C-1, C-3, N-2, and N-9 strongly influence important properties such as lipophilicity, membrane permeability, and biological potency. Compound 15a bearing fatty alcohol hybrid at C-3 position has a very low MIC value at 2.8 μg/mL against Bacillus subtilis MTCC 121, dimeric N2-benzylated quaternary salts displayed an exceptional low MIC value at 0.01-0.05 μmol/mL against MRSA and 1-hydrazide derivatives shows a potent antifungal efficacy by exhibiting EC50 lower than 0.23 μg/mL. In particular, N-quaternization, lipophilic chain introduction, and hybridisation with active pharmacophores can significantly enhance antimicrobial activity. Overall, β-carbolines remain promising scaffolds for future anti-infective drug development.
Nadhirah Najwa Mohd Farith, Nurul Shafiqah Zamri, Karimah Kassim et al.· Natural Product Research· 0 citations
Spirooxindoles are a class of spirocyclic scaffolds in drug discovery, as the rigid frame and well-defined substitution pattern can interact with various biological targets. Recent advances in synthetic methodologies, including multicomponent 1,3-dipolar cycloadditions, organocatalytic cascades, and one-pot protocols, have facilitated the efficient synthesis of a wide variety of derivatives for SAR studies. A diverse range of classes, including pyrrolidine, cyclopropyl carboxamide, carbamate, oxadiazoline, pyrrolizidine, and furan derivatives, show cytotoxicity in the submicromolar-to-low micromolar range with good selectivity. The SAR studies suggest that substitution on the isatin core generally enhances biological activity in individual series, especially with electron-withdrawing groups, but these effects are scaffold dependent. Furthermore, spirooxindole derivatives have been reported to show antibacterial activity, including TrpRS inhibition, antimicrobial, acetylcholinesterase inhibition, α-glucosidase inhibition, antiviral, and anticonvulsant activities. The recent patents, especially on MDM2 inhibitors and other anticancer agents with nanomolar potency, provide further evidence for the continued interest in spirooxindole-based drug discovery. This review highlights the recent advancements in spirooxindole chemistry involving synthetic strategies, SAR, biological activities, and recent patents.
R. Kalita, Sarbanga Bezbaruah, D. Patle· ChemMedChem· 0 citations
This review covers published data (mostly from 2019 to 2025) on the synthesis and biological activity of azolo[a]quinoxalines, including pyrazolo-, imidazo- and triazolo-annelated systems. We highlight that most research efforts are directed toward the design of anticancer agents, with additional applications as Toll-like receptor antagonists, monoamine oxidase inhibitors, opioid receptor modulators, PI3Kα inhibitors, tubulin polymerization inhibitors, GABAᴀ receptor modulators, VEGFR-2 kinase inhibitors, BRD9 binders, and anti-inflammatory, antimicrobial, and antifungal agents. Recent synthetic strategies include Cu-catalyzed oxidative annulations, I2-mediated C–H functionalization, metal-free cascade cyclization, and multicomponent reactions, often employing eco-friendly catalysts and reductants. A growing number of studies integrate virtual screening, molecular docking, and pharmacophore-based in silico approaches to guide lead discovery and optimization. Innovative drug delivery systems, such as nanogels and hybrid molecules combining azoloquinoxalines with pharmacophores like thalidomide, have also been explored. This review emphasizes both the medicinal chemistry aspects of azolo[a]quinoxalines and the synthetic methodologies for their preparation from the perspective of drug development and discovery.
E. Nosova, G. Lipunova, V. N. Charushin· Molecules· 0 citations
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