The chemistry of common drug-related heterocycles. Part I – aromatic monocyclic six-membered heterocycles containing one or two nitrogen atoms

Aromatic six-membered nitrogen-containing heterocycles, collectively referred to as azines, are common structural motifs in pharmaceuticals and natural products. Their aromatic yet polar character enables a diverse array of noncovalent interactions with pharmacodynamic targets, including π–π stacking, dipolar contacts, and hydrogen bonding. In addition, the basicity of their endocyclic nitrogen allows protonation, modulating their solubility and improving pharmaceutical formulation properties. Owing to these structural and physicochemical features, azines display a wide range of pharmacological activities and are strongly represented among FDA-approved drugs. This review highlights the chemistry of the major azine scaffolds, namely pyridine, pyrimidine, and pyrazine, focusing on both classical and modern strategies for their efficient and selective synthesis and functionalization.