Indolizine: A Comprehensive Review of Their Chemistry, Synthesis and Application

Indolizines are a unique class of bridgehead nitrogen-fused heteroaromatic compounds. They act as bioisosteres of indole, which is an important structure in medicinal chemistry. Their rigid aromatic framework, resonance stabilisation, and strong fluorescence support various chemical and biological uses. Improvements in synthetic methods, such as the Tschitschibabin reaction, 1,3-dipolar cycloadditions, and metal-catalysed cyclisations, have made it easier to create different indolizine derivatives with better yields and selectivity. Substituted indolizines show remarkable stability and resistance to nucleophilic attack, while still being highly reactive toward electrophiles. Biologically, indolizine derivatives have a wide range of activities, including antidiabetic, antimicrobial, anti-inflammatory, anticonvulsant, anticancer, antioxidant, and enzyme-inhibitory effects. They are notably effective as potent 15-lipoxygenase inhibitors. Their versatility goes beyondpharmacology into material science, where their fluorescence and stability increase their usefulness. Although some reactive sites remain underexplored, ongoing research is expanding the structural diversity and therapeutic potential of indolizines. Together, these compounds continue to be valuable structures that drive progress in drug discovery and functional materials.