Beyond the Shadow of Indole: Medicinal Chemistry of Indolizines and Isoindolinones in the Fight Against Infectious Diseases

Infectious diseases remain a major global health challenge, accounting for millions of deaths annually and placing an increasing burden on healthcare systems worldwide. The rapid emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacterial strains, together with recurrent outbreaks of viral infections such as SARS-CoV-2, Ebola, Zika, Monkeypox, and influenza, underscores the urgent need for novel therapeutic agents with diverse mechanisms of action. In this context, indolizines, isoindoles, and isoindolinones represent promising scaffolds in anti-infective drug discovery due to their unique structural features, versatile reactivity, and ability to engage multiple biological targets. This review provides an updated overview of the medicinal chemistry of indolizine and isoindoles, with particular emphasis on compounds demonstrating activities against infectious pathogens. Representative examples are highlighted to illustrate structure–activity relationships (SARs), scaffold-based optimization strategies, and emerging mechanistic insights. Relevant synthetic methodologies are discussed only in the context of biologically active compounds to provide a framework for rational design. Collectively, this review underscores the therapeutic potential of indolizine- and isoindole-derived scaffolds as versatile frameworks for anti-infective drug development and highlights opportunities for further chemical and biological exploration.