Oxadiazole Derivatives: A Comprehensive Review of Their Chemistry, Synthesis, and Pharmacological Potential

Abstract

Heterocyclic compounds are circular in shape having at least one N, S or O atom in place of carbon (other atoms boron, silicon etc can also take part). They have a significant role as part of natural biological compounds as well as synthesized derivatives. This study is taken from several research as well as review articles, book chapters, reports from Google scholar, PubMed, NIH, Research Gate, Academia, WHO’s official website. Oxadiazole derivatives represent a crucial class of nitrogen-containing heterocyclic compounds with broad applications in medicinal, pharmaceutical, and polymer chemistry. Among their four isomeric forms 1,2,3-, 1,2,4-, 1,2,5-, and 1,3,4-oxadiazoles the 1,2,4- and 1,3,4-isomers are of particular interest due to their chemical stability, aqueous solubility, and strong pharmacological profiles. These scaffolds exhibit diverse biological activities, including antibacterial, antifungal, antiviral, anticancer, antitubercular, anti-inflammatory, and anticonvulsant properties. Their utility is further highlighted by their presence in approved drugs such as raltegravir and investigational candidates like ataluren and zibotentan. The electron-deficient nature of the oxadiazole ring, attributed to multiple heteroatoms, enhances its metabolic stability and allows for functionalization via nucleophilic substitution, especially in halogenated derivatives. Strategic substitution with electron-withdrawing groups (e.g., p-NO₂, p-Cl) has been shown to enhance biological activity through improved pharmacokinetic and pharmacodynamic properties. Various synthetic methodologies, from classical approaches to green chemistry techniques, have enabled efficient production of oxadiazole derivatives. Given their structural diversity, chemical resilience, and potent bioactivity, oxadiazole compounds continue to offer significant potential for drug discovery and therapeutic innovation. This review highlights their synthesis, structural characteristics, and multifaceted pharmacological applications, supporting their continued exploration in modern medicinal chemistry.