The starting 5-cyano-6-(3,4-dimethoxyphenyl)-2-thiouracil 1 which prepared by reaction of ethyl cyanoacetate with thiourea and 3,4-dimethoxybenzaldehyde, was allowed to react with POCl3/PCl5 to give the key intermediate 4- chloropyrimidine-2-thione derivative (2). Compound 2 underwent several substitution reactions with sulfa drug, pamino acetophenone and benzocaine to give the corresponding substituted 4-amino derivatives 3, 4, 6, respectively. The hydrazides 5, α,β-unsaturated ketone 7 and its cyclized products 8, 9 were also prepared. The imidazopyrimidinthione 10, its Mannich bases and arylmethylene derivatives 11 and 12 were also prepared. Several other pyridoimidazopyrimidine-thiones and triazolopyrimidines were also synthesized. All newly prepared compounds were biologically evaluated for their anticancer activity against cancer cell lines.