Chemistry of Hypoxanthine: Advancement in Derivatization and Drug Development

Abstract Heterocyclic compounds, especially nitrogen‐containing ones, have emerged as central focus in organic synthesis, driven by their vast synthetic versatility and functional utility. Hypoxanthine and its derivatives have long intrigued chemists due to their distinctive chemical structure and versatile biological properties. As a key purine derivative involved in nucleotide metabolism, hypoxanthine plays a vital role in many cellular processes. Recently, it has been investigated as a biomarker for various diseases including hypoxia, multiple sclerosis, colorectal cancer, Alzheimer's and cardiac ischemia. Its derivatives attracted much attention nowadays owing to their diverse biological profile such as antiviral, antimicrobial, and antimalarial effects. The flexibility to modify hypoxanthine's core structure has facilitated the creation of numerous therapeutic agents, positioning hypoxanthine as a key subject of interest in medicinal chemistry and drug design. This review primarily targets on the methodologies for synthesizing hypoxanthine derivatives and assists the future researcher for developing bioactive scaffolds with enhanced pharmacokinetics and clinical translation by advancement in prodrug design.