Dihydropyrimidines as Multifaceted Scaffolds: A Comprehensive Review of Synthetic Approaches and Biological Significance

Abstract:

Dihydropyrimidines (DHPMs) are an important class of heterocyclic compounds with broad pharmacological and therapeutic potential. Among the various synthetic routes for assembling the DHPM frame, the classical Biginelli reaction remains the most effective and widely used method due to its convenient one-pot procedure. Structurally, DHPMs offer valuable flexibility, enabling the incorporation of numerous functional groups to enhance pharmacological properties. This review highlights key pharmacological activities of DHPMs, including antihypertensive, anticancer, calcium channel-blocking, anti-inflammatory, antiviral, antitubercular, anticonvulsant, analgesic, antimicrobial, lipoxygenase inhibitory, xanthine oxidase inhibitory, and urease inhibitory effects, while focusing on recent developments in synthetic methods and structure-activity relationship (SAR) studies relevant to the advancement of therapeutically active molecules. The article further discusses how these diverse properties inspire the rational design and structural modification of new dihydropyrimidine derivatives to yield more effective, selective, and safer drug candidates for various clinical applications. This review underlines the dihydropyrimidine framework’s biological significance and its advancing potential in therapeutic innovation and medicinal chemistry.