The design of novel antagonists for adenosine A2a receptor (A2a AR) is a promising strategy for the development of new-generation anticancer agents. 5-Alkylamino-7-aminoazolo[1,5-a]pyrimidin-6-carbonitriles proposed in this work are close structural analogs of known nanomolar A2a AR antagonists. An efficient synthetic strategy towards the functional derivatives of the target heterocycles is cyclocondensation of aminoazoles with 2-[(alkylamino)(methylsulfanyl)methylene]malononitriles on heating in DMF in the presence of ButOK. The obtained azolopyrimidine-6-carbonitriles do not show statistically significant cytotoxic effect on human embryonic kidney cells, while 2-methyl- and 2-(furan-2-yl)azolopyrimidines inhibit the viability of lung carcinoma and hepatocellular carcinoma cells with IC50 values in the low micromolar range.