2-Pyridone as privileged scaffold: Advances in drug design and structural modification.

The 2-pyridone scaffold constitutes a privileged and versatile heterocyclic framework in medicinal chemistry. Existing reviews have largely concentrated on synthetic methodologies, and a comprehensive overview of this scaffold in medicinal chemistry remains lacking. This review systematically surveys the applications of 2-pyridone-based compounds from 2010 to 2026, with an emphasis on design strategies, structure-activity relationships (SAR), druggability optimization, and biological activities. The applications of these derivatives span diverse disease categories, including cancer, infectious diseases, central nervous system (CNS) disorders, as well as immunological, metabolic, and cardiovascular conditions. Notably, the scaffold has demonstrated distinct value in the development of highly selective kinase inhibitors. In summary, the 2-pyridone scaffold continues to provide a robust and adaptable platform for the discovery of next-generation therapeutics, and this review aims to serve as a comprehensive reference for rational drug design while inspiring novel insights into the development of 2-pyridone-based drug candidates.