Medicinal Chemistry of Sultams and Heterocyclic Compounds

The medicinal chemistry of sultams—a class of cyclic sulfonamides—and related heterocyclic compounds has witnessed remarkable progress in recent years. Sultams combine the chemical stability of sulfonyl groups with the conformational rigidity of cyclic frameworks, conferring unique patterns of molecular recognition and bioavailability. Heterocycles containing nitrogen, sulfur or oxygen atoms are ubiquitous in pharmaceuticals, serving as core scaffolds for antibacterial, antifungal, anti-inflammatory and anticancer agents. Advances in synthetic methodology, including cascade reactions and green protocols, have enabled rapid access to diverse ring systems from simple precursors. Computational approaches such as density functional theory (DFT) modelling and structure-based design now guide the optimisation of ligand–protein complementarity, accelerating lead identification. Moreover, the introduction of fluorinated moieties and chlorinated substituents has enhanced metabolic stability and receptor selectivity. Collectively, these developments underline the global significance of sultams and heterocycles in tackling antimicrobial resistance, oncology and chronic inflammatory disorders, while meeting the growing demand for sustainable and efficient synthetic routes.

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Medicinal Chemistry of Sultams and Heterocyclic Compounds publication trend

The graph below shows the total number of articles in medicinal chemistry of sultams and heterocyclic compounds across all publications each year (not limited to Nature Index journals).

Technical terms

Sultam: A cyclic sulfonamide featuring a sulfonyl (–SO₂–) bonded within a ring.

Heterocycle: A ring system in which one or more ring atoms are elements other than carbon (e.g. N, O, S).

Cascade reaction: A sequence of bond-forming events occurring in one pot without intermediate isolation.

Thiol–isothiocyanate coupling: A click-type reaction forging C–S bonds from thiols and isothiocyanates.

DFT calculations: Density functional theory methods for predicting electronic structure and reaction pathways.

5-endo-dig cyclisation: A ring-closure mode following Baldwin’s rules to form five-membered rings via internal nucleophilic attack.

References

1. Green Synthesis of 2-Mercapto 5,6-Dihydro-4H-1,3-Thiazines via Sequential C–S Couplings. Molecules (2024).
2. TBAF-promoted carbanion-mediated sulfonamide cyclization of CF 3 -substituted N -allenamides: an access to fluorinated γ-sultams. Organic Chemistry Frontiers (2023).
3. Recent Advances in Catalytic Synthesis of Benzosultams. Molecules (2020).
4. A Review on Medicinally Important Heterocyclic Compounds. The Open Medicinal Chemistry Journal (2022).
5. Lead Generation and Optimization Based on Protein-Ligand Complementarity. Molecules (2010).