DHPMs

DHPMs refers to dihydropyrimidinones, a family of heterocyclic compounds characterized by a partially saturated pyrimidine ring bearing a lactam carbonyl at position 2. The canonical core is 3,4-dihydropyrimidin-2(1H)-one, typically formed as a result of multicomponent condensation and cyclization. The ring substituents are derived from the starting materials, allowing substantial structural diversity across DHPM derivatives.

Synthesis of DHPMs is most commonly accomplished via the Biginelli reaction, a one-pot, acid-catalyzed condensation of a β-ketoester, an aldehyde, and urea (or thiourea). Over the years, numerous variants have been developed, employing different acid catalysts, Lewis or Brønsted acids, and solvent systems or solvent-free conditions. The reaction tolerates a wide range of aldehydes and β-ketoesters, enabling the rapid generation of diverse DHPM libraries.

Structure and properties of DHPMs center on the six-membered heterocycle containing two nitrogens (1,3-dihydropyrimidinone) with a carbonyl at C-2. Substitution at the N1 and various ring positions (through the choice of reagents) yields a broad array of derivatives. DHPMs are typically non-aromatic, and their physicochemical properties can be tuned via substituents to influence biological activity and pharmacokinetic profiles.

Applications and research: DHPMs are widely explored as drug-like scaffolds in medicinal chemistry. A substantial body of derivatives has demonstrated diverse biological activities, including antiviral, anticancer, antimicrobial, anti-inflammatory, and enzyme-inhibitory effects. In addition to pharmacological use, DHPMs serve as building blocks and intermediates in organic synthesis, with ongoing studies to map structure–activity relationships and to optimize synthetic methodologies.