Synthesis and anticancer evaluation of some novel N,O,S heterocyclic compounds pendant to 3-methyl-5-cyano-6-(3,4-dimethoxyphenyl)pyrimidine and other related fused pyrimidines
Abstract
The key starting compound 5-cyano-6-(3,4-dimethoxyphenyl)-2-thiouracil (1) was synthesized and allowed to undergo electrophilic substitution with methyl iodide to give the corresponding 6-(3,4-dimethoxyphenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydro-pyrimidine-5-carbonitrile (2). Nucleophilic substitution on compound 2 with hydrazine hydrate led to the corresponding 2-hyrazinopyrimidone intermediate 3. Compound 3 underwent several substitution and cyclization reactions with β-ketoester, β-ketone, alkyl halides, arylisothiocyanate, or aromatic aldehydes followed by cyclization reactions to give the corresponding N,O,S heterocyclic compounds incorporated into pyrimidine moiety and/or the related S-triazino[3,4-b]pyrimidine derivatives 4-18. Anticancer evaluation of some representative examples of newly synthesized compounds was carried out against MCF-7, HCT116 cell lines. Some of the newly synthesized compounds showed significant activity.