Synthetic approaches to unsymmetrical 2,5-disubstituted 1,3,4-oxadiazoles and their MAO-B inhibitory activity. A review

• Actual classification of synthetic approaches for 2,5-disubstituted 1,2,4-oxadiazoles. • Novel and highly efficient methodologies developed for the synthesis of 1,2,4-oxadiazoles have been described in the article. • Promising inhibitory MAO B potency in a nanomolar concentration range of 2,5- disubstituted 1,2,4-oxadiazoles. • Different substitution patterns of the oxadiazole determine MAO B inhibition and selectivity. Selective monoamine oxidase type B (MAO-B) inhibitors are currently used as coadjuvants for treating early motor symptoms of Parkinson’s disease. Aiming at the elucidation of MAO-B inhibitors with 1,3,4-oxadiazole scaffolds, we make a comprehensive update on the new and old chemical methods employed for the synthesis of the unsymmetrical oxadiazole derivatives that lead to high yield compounds. We summarize a state of the selective MAO-B inhibitors with oxadiazole scaffold, describing the results, structures, structure-activity relationships (SARs) and medicinal chemistry strategies over the years. The analysis of the recent papers would facilitate tracking the increasing number of oxadiazole derivatives as new chemical spaces with MAO-B inhibitory potential designed to ensure the safe use of the compounds and elimination of the unwanted drug-drug interactions.