Recent Applications of Hydantoins in Drug Discovery: Updates (2019~Present).

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.