Mercaptopyrimidin 1 was subjected to an acidic medium reaction with urea and aromatic aldehydes, yielding pyrimidopyrimidine 5a,b via unsaturated system 3, followed by 1,4 additions and subsequent H2S elimination. Using thiourea and/or guanidine instead of urea in the aforementioned process yielded pyrimidines of type (5 c-f). Condensation of benzaldehyde and its derivatives with compound 1 is followed by H-shift and oxidative cyclization, resulting in polycyclic compounds. 7. To make ozoloazines 9a-b, compound 7 undergoes a substitution reaction with urea and thiourea, followed by air oxidation. The cyclocondensation of hydrazides derivatives yielded triazolopyrimidines (12 a, b). In vitro, all novel pyrimidine derivatives were tested for antiproliferative activity against two cell lines: human gastric carcinoma (BGC-823) and human lung cancer (A-549). The results were compared to the NIH/3T3 murine fibroblast cell line. Some of these compounds, in particular 5a–f, 6,8,10a-b and 12a-b, were discovered to be the most effective derivatives against all cancer cell lines, with no impact on normal cells. Using the structure–activity connection as a guide, compound 10b has a greater activity against A-549 cells (IC50= 14.15 0.33 g/ml), as it contains thiadiazolidine imine nucleus which attached to thio pyran ring.