Synthesis of new substituted 3-(1,2,4-oxadiazol-5-yl)- thieno[3,2-e][1,2,3]triazolo[1,5-a]pyrimidin-5(4h)-ones via azide domino reactions

Fused polyheterocyclic compounds related to thieno[2,3-d]pyrimidines are a widely-used class of heterocycles in medicinal chemistry and have attracted considerable interest as potential anticancer agents. In the current article, the substituted (1,2,4-oxadiazol-5-yl)acetonitriles were implemented in convenient domino reactions with 2-azidothiophene-3-carboxylates for the straightforward synthesis of 3-(1,2,4-oxadiazol-5-yl)-thieno[3,2-e][1,2,3]triazolo[1,5-a]pyrimidin-5(4H)-ones. The 1,2,4-oxadiazole motif was selected to be conjugated with thieno[3,2-e][1,2,3]triazolo[1,5-a]pyrimidine core because several (1,2,4-oxadiazol-5-yl)-1H-1,2,3-triazol-5-amines recently was found as promising antitrypanosomal activity, which is often tied to cytotoxicity against cancer cells. The reaction proceeds at room temperature in a short time with base catalysis and no chromatographic purification of products is required. High purity products were isolated by simple filtration. The synthesized compounds were screened for anticancer activity in the 60 cancer cell panel in NCI. In general, selected 3-(1,2,4-oxadiazol-5-yl)thieno[3,2-e][1,2,3]triazolo[1,5-a]pyrimidin-5(4H)-ones did not show significant antitumor activity. The highest activity was demonstrated by compound 3b, which inhibited the growth of 27% of LOX IMVI melanoma cells at a concentration of 10-5 M.