LAUSR

A novel chemotype of nitrile‐containing azolopyrimidines with potential antitumor activity has been proposed, and a method for the synthesis of the corresponding 5‐amino‐7‐oxoazolo[1,5‐a]pyrimidine‐6‐carbonitriles by cyclocondensation of various aminoazoles and ethyl 2‐cyano‐3‐R‐amino‐3‐(methylsulfanyl)acrylates has been developed. Cytotoxic effects of the obtained azolopyrimidines against glioblastoma (A‐172), bladder carcinoma (T‐24), lung carcinoma (A‐549), and human embryonic kidney (HEK‐293) cells have been investigated, and structure–activity relationships have been identified. 2‐Phenyl‐5‐(morpholin‐4‐yl)‐7‐oxo‐1,2,4‐triazolo[1,5‐a]pyrimidine‐6‐carbonitrile 5j has been found to exhibit selective cytotoxic activity against the T‐24 cells (IC50 = 14.68 µM), whereas 3‐bromo‐5‐(morpholin‐4‐yl)‐7‐oxopyrazolo[1,5‐a]pyrimidine‐6‐carbonitrile 5v has shown selective toxicity against the A‐172 cells (IC50 = 18.38 µM). Further studies on heterocycle 5j in the annexin V apoptosis assay indicate that the primary mechanism involves inhibition of proliferative activity rather than induction of cell death. The cyclin‐dependent kinase 2 protein is suggested as a possible target for the cytotoxic action of the studied compounds 5 on the T‐24 cell line according to the notable correlation between docking studies and MTT assay results.