Recent advances in the development of selective human MAO-B inhibitors: (Hetero)arylidene-(4-substituted-thiazol-2-yl)hydrazines

A large series of (4-substituted-thiazol-2-yl)hydrazine derivatives was synthesized in good yield and assayed for their in vitro human monoamine oxidase (hMAO) inhibitory activity and selectivity. Most of them showed inhibitory activity in the nanomolar range and hMAO-B selective inhibition higher than reference drugs, demonstrating our interest in this privileged scaffold. The structure–activity relationship of the different rings on the N1-hydrazine position indicated that a pyridine ring was preferred with the presence of electron-withdrawing substituents on the aryl group at C4 of the thiazole nucleus. The substituent on the α-carbon to the N1-hydrazine moiety (methyl or hydrogen) had a great influence on the activity and hMAO-B selectivity. Moreover, the reversibility of the enzyme inhibition for the best active compound was reported.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Synthesis of a large number of hydrazothiazole derivatives. ► Most of them displayed an interesting hMAO inhibitory activity with a better hMAO-B selectivity. ► Only smaller heterocyclic substituents on the N1-hydrazine were tolerated. ► (Hetero)arylthiazolylhydrazines acted as reversible MAO-B inhibitors.