The State of Imidazolone as an Evolving Pharmacophore: Current Progress and Clinical Significance in Oncology and AMR

Nitrogen-bearing heterocycles have been fundamental scaffolds in drug discovery, contributing significantly to the design and development of therapeutic agents since the inception of modern medicinal chemistry. Among them, imidazolones have shown notable therapeutic relevance, particularly in oncology, antimicrobial resistance (AMR), and inflammation, yet they remain relatively underexplored. Nevertheless, the significant therapeutic and clinical efficacy of imidazolone-bearing drugs, such as Nilutamide, Irbesartan, and Leucettinib-21, in anticancer, antihypertensive, and neurotherapeutic applications has stimulated increasing interest in imidazolone chemistry and its medicinal potential. This review systematically discusses the major synthetic strategies, structure-activity relationships, and mechanistic principles governing the biological activity of imidazolones. Particular emphasis is placed on their rapidly expanding role as anticancer agents targeting enzymes and signaling proteins such as carbonic anhydrases, epidermal growth factor receptors (EGFR), Bcl-2 protein family, and checkpoint kinases, along with their potential applications in antimicrobial and anti-inflammatory therapies. Furthermore, the review highlights the complementary roles of computational modeling and biological evaluation in understanding the interactions of imidazolone-bearing compounds with various microbial and cancer-related receptors. These integrated studies reveal their ability to engage multiple biological targets and validate their observed pharmacological activities. The convergence of in silico predictions with experimental findings offers valuable guidance for the rational development of imidazolone-based therapeutics. Overall, this review emphasizes imidazolones as promising scaffolds with significant potential for future drug discovery and development.