Recent Update (2015-2025) on Synthesis of Anti-inflammatory Pyrimidine Derivatives

Pyrimidines and their derivatives constitute an important class of six-membered aromatic heterocyclic compounds due to their widespread occurrence in biologically active molecules and their therapeutic and synthetic organic chemistry applications. Pyrimidine derivatives have been found to exhibit numerous biological activities, such as anti-cancer, anti-bacterial, anti-diabetic, anti- inflammatory, anti-viral, anti-oxidant, and anti-fungal. In recent years, increasing attention has been directed toward the development of novel pyrimidine derivatives as potential antiinflammatory agents, driven by the need for safer and more effective alternatives to conventional non-steroidal anti-inflammatory drugs. Recent studies have highlighted their potential as antiinflammatory agents because they can suppress the expression and activity of several key inflammatory mediators. This review discusses recent advances in the synthesis of pyrimidine derivatives and pyrimidine-fused five- and six-membered heterocycles, and their Structure-Activity Relationships (SARs). The synthesis of pyrimidine and fused pyrimidine derivatives from starting materials such as enamines, guanidines, and malonitriles is also discussed, including cyclization, substitution, and cycloaddition reactions, is also discussed. The remarkable synthetic versatility of pyrimidine derivatives further highlights their importance as promising anti-inflammatory agents.