Structure- Activity Relationship Insights into Dihydropyrimidinones (DHPMs): A Versatile Scaffold for Multitarget Drug Discovery

Abstract

Dihydropyrimidinones (DHPMs), a group of heterocyclic compounds that are considered versatile compounds bearing significant potential in multitarget drug discovery and development. Due to their adaptable nature, DHPMs demonstrate a wide range of pharmacological activities. Additionally, the implementation of green synthesis methods, such as solvent-free and microwave-assisted reactions, enhanced DHPM production efficiency by reducing reaction time from 2-4 hours to 10-20 minutes, increasing yields up to 95%, and lowering energy consumption by 40%, thereby improving environmental sustainability through a 60% reduction in hazardous waste. This review presents a wide-ranging consideration of the structural activity relationships (SAR) of DHPM derivatives, highlighting how specific substitutions (e.g. electron-donating, electron-withdrawing groups) at various positions on the DHPM core impact their biological activities. Hybridisation and In-silico methodologies have emerged as pivotal tools for enhancing lead identification and optimisation. Techniques such as quantitative structure-activity relationship (QSAR), virtual screening, and molecular modeling have allowed precise evaluation of DHPM-target interactions, facilitating SAR refinement. By elucidating the SAR of DHPMs, this review aims to guide future research in the rational design of more potent DHPM-based therapeutics, facilitating the development of more effective and safer drugs across various therapeutic areas.