Synthesis and modification of 7-aroyl derivatives of 4,7-dihydro-[1,2,4]triazolo-[1,5-a]-pyrimidine as potent inhibitors of sirtuin-2

Sirtuin-2 (SIRT2) is a member of the human sirtuin class that regulates various biological processes and is considered a novel biomarker for numerous types of cancer. Depending on the type of tumor, SIRT2 knockout leads to a controversial role in tumorigenesis. However, pharmacological inhibition of SIRT2 with small molecules leads exclusively to inhibition of the growth of many cancer cells, thus opening the way to the therapy of oncological diseases. In this work, we synthesized 7-aroyltriazolo[1,5-a]pyrimidine derivatives (some of which showed good inhibitory activity) and modified the active functional groups of the bicyclic structure. The effect of functionalization of the nitrogen atom and the influence of the oxidation and reduction of the dihydropyrimidine fragment on the inhibitory activity of the studied derivatives against sirtuin2 was analyzed by molecular docking calculations.