Recent advances in piperidones as privileged scaffolds for drug discovery and development.

Piperidone, a chemically versatile cyclic amine incorporating a ketone functional group, has emerged as a privileged scaffold in contemporary drug design owing to its synthetic adaptability and wide range of biological activities. This review provides a comprehensive overview of piperidone and piperidone-containing compounds that have been synthesized in laboratories, isolated from natural sources, or identified in marine organisms. Various synthetic strategies for constructing the piperidone scaffold are discussed, including multicomponent reactions, cycloadditions, organocatalytic methods, and microwave-assisted one-pot protocols. Piperidone derivatives exhibit a broad spectrum of biological activities, including antioxidant, anti-inflammatory, antimicrobial, antifungal, antiviral, neuroprotective, and, notably, anticancer effects across diverse cell lines. Interestingly, several derivatives exert their anticancer effects via more than one mechanism simultaneously, underscoring the importance of detailed structure-activity relationship (SAR) studies to delineate structural determinants responsible for specific modes of action. A deeper understanding of these mechanistic relationships could enable the rational design of novel piperidone-based molecules capable of targeting multiple pathways concurrently, thereby enhancing therapeutic efficacy. Moreover, investigating natural biosynthetic routes may facilitate scalable production of structurally complex piperidone derivatives, unlocking new opportunities in medicinal chemistry and drug development. Overall, this review highlights the significance of the piperidone scaffold as a key structural motif in rational drug design.