Copper-Catalyzed C─N and C─S Bonds Formation Approach Toward the Synthesis of 1H,6H-Benzo[d]pyrimido[2,1-b][1,3]thiazin-1-ones: Evaluation of Their Cytotoxic Activities Against Cancer Cell Lines

A copper(I)-catalyzed regioselective strategy has been put forth toward the effective synthesis of 1H,6H-benzo[d]pyrimido[2,1-b][1,3]thiazin-1-ones 4 via the cascade intermolecular S-benzylation and intramolecular N-arylation processes. The developed method has been accomplished by the reaction between 2-iodobenzyl bromides 1 and 2-thioxo-2,3-dihydropyrimidin-4(1H)-ones as the easily available substrates under the influence of Cu(I)-catalyst to afford the corresponding product 4 in yields up to 89%. The resulting N-heterocyclic moieties were examined for cytotoxic activities against cancer cell lines. It was investigated that the molecule 4a was effective against Leukemia (K562) cell lines with acceptable IC₅₀ value of 10.0 ± 2.9 µM; molecules 4d, 4j, 4q, and 4r were moderately active against MCF-7 breast cancer cell lines and compounds 4a, 4d, 4n, 4q, and 4r were also found to exhibit moderate activities against MDA-MB-231 breast cancer cell lines. Further modifications of these bioactive molecules may lead to effective anticancer drug candidates.