2‐substituted tricyclic oxazolopyrimidine library: Design, synthesis, and cytotoxicity activity

We report the design, synthetic route, and cytotoxicity of a library of 49 newly synthesized tricyclic oxazolo[5,4‐d]pyrimidines. The condensed pyrimidinones were constructed from ethyl 5‐aminooxazole‐4‐carboxylate building blocks. A tricyclic ring system was built using the naturally occurring mackinazolinone alkaloid with a focus on the molecular diversity at position C‐2 of the oxazole ring. Synthesized compounds were evaluated against a panel of human cancer cell lines including MCF‐7 (breast), HeLa (cervical), and A549 (lung) in vitro. The results revealed that substitution of halogen‐related aromatic fragments at position C‐2 of the oxazole ring may serve as promising anticancer drug candidates.