Synthesis, in silico and in vitro Evaluation of Novel Oxazolopyrimidines as Promising Anticancer Agents

New potential bioactive oxazolopyrimidines have been synthesized using two main approaches: the pyrimidine ring annulation on a functionalized oxazole and the benzoyl bromide trimerization followed by rearrangement and formation of the oxazolo[5,4‐ d ]pyrimidine scaffold. The docking analyzes have shown that 7‐piperazine substituted oxazolo[4,5‐ d ]pyrimidines 8a – 8c could be potential VEGFR2 inhibitors with high free energy of ligand–protein complex formation (Δ G : −10.1, −9.6, −9.8 kcal/mol, respectively). In vitro antitumor assays confirmed theoretical predictions that oxazolo[4,5‐ d ]pyrimidines 8a – 8c containing positively charged piperazine moiety should demonstrate significantly higher cytotoxic effects. 4‐[5‐(4‐Chlorophenyl)‐2‐phenyl[1,3]oxazolo[4,5‐ d ]pyrimidin‐7‐yl]piperazin‐1‐ium trifluoroacetate ( 8c ) exhibited a slightly higher antiproliferative effect ( IC 50 =0.21 μ m ) than doxorubicin ( IC 50 =0.36 μ m ) on MDA‐MB‐231 cell line and has relatively good results on OVCAR‐3 ( IC 50 =1.7 μ m ) and HCT‐116 ( IC 50 =0.24 μ m ) cells.