Ferreira_2026_ACS.Omega_11_2348

Imidazo-[1,2-a]-pyridines are widely recognized scaffolds present in several marketed drugs, including the anxiolytics alpidem, saripidem, necopidem, and zolpidem, which are some of the most prescribed medications for insomnia. In this review, we analyze publication trends, which reveal exponential growth in research involving this scaffold. We highlight recent synthetic strategies (2017-2025) for the preparation of imidazo-[1,2-a]-pyridine derivatives, such as condensation, multicomponent and tandem reactions, intramolecular cyclizations, and oxidative couplings under green conditions. In addition, we discuss innovative Medicinal Chemistry studies exploring their applications in the treatment of cancer, Alzheimer's disease, tuberculosis, and neglected tropical diseases. Significant advances have been made in identifying derivatives with potent activity against specific biological targets, including kinases, tubulin, HDACs, the cytochrome bc1 complex of Mycobacterium tuberculosis, and key enzymes involved in the pathogenesis of Alzheimer's disease, such as cholinesterases and secretases. Altogether, this review consolidates the vast therapeutic potential of the imidazo-[1,2-a]-pyridine core, emphasizing its synthetic versatility and broad spectrum of biological activities, which firmly establish it as a privileged scaffold for drug discovery.