Tandem Cyclization–Ring Opening of Chromenylamidines: A Direct Route to Pyrido[2,3‍‐‍ d ]pyrimidin‐4(1 H )‐Ones With Anticancer Activity

Pyrido[2,3‐ d ]pyrimidinones can be considered privileged heterocyclic scaffolds as they are present in a diversity of molecules with a wide range of biological activities. This work describes a novel synthesis of pyrido[2,3‐ d ]pyrimidin‐4(1 H )‐ones from chromenylamidines by a cascade cyclization–ring‐opening reaction, induced by acetic acid catalysis and heating in ethanol. Preliminary biological evaluation identified several derivatives with significant and selective cytotoxic activity for triple‐negative breast cancer cell lines (low micromolar EC ₅₀ values). This methodology provides a straightforward approach to 1,5,7‐triarylpyridopyrimidinones from readily available 4 H ‐chromene precursors, enabling access to a library of compounds with promising cytotoxic activity in cancer cell models.