Imidazo[1,2- a ]pyridines as Privileged Scaffolds: Synthetic Advances, Biological Activities, and Translational Challenges

Abstract

Imidazo[1,2-a]pyridine derivatives are privileged scaffolds in medicinal chemistry due to their structural versatility, favorable physicochemical properties, and broad pharmacological relevance. Their fused heterocyclic framework enables extensive functionalization while preserving conformational rigidity and optimal heteroatom distribution, making this core highly attractive for drug discovery. This systematic review summarizes recent advances (last 5 years) in the synthesis, structural diversification, and biological evaluation of imidazo[1,2-a]pyridine-based compounds. A comprehensive literature search was performed using the Scopus and Web of Science databases, focusing on studies reporting relevant biological data. The reviewed derivatives display diverse pharmacological activities, including anticancer, antimicrobial, antitubercular, antifungal, antiparasitic, neuroactive, anti-inflammatory, antidiabetic, and ferroptosis-modulating effects. Emphasis is placed on structure–activity relationships, scaffold-hopping strategies, and emerging hybrid designs. Despite promising in vitro potency against multiple therapeutic targets, important limitations remain. Many compounds still lack in vivo validation, pharmacokinetic characterization, and ADME/Tox optimization, restricting their progression toward preclinical development. In addition, structural exploration remains concentrated on conventional substitution patterns, underscoring the need for broader bioisosteric and fragment-based approaches. Overall, this review consolidates recent advances, highlights critical knowledge gaps, and outlines future directions for the rational development of imidazo[1,2-a]pyridine-based therapeutics.