| Abstrakt: |
2-Amino-6-sulfanylidene-5,6-dihydropyrimidin-4(3H)-one (1) was subjected to reaction with urea and aromatic aldehydes in acidic medium to yield pyrimido[4,5-d]pyrimidines 5a and 5b through intermediate formation of 5-arylmethylidene derivative 3, followed by 1,4-addition and cyclization with elimination of hydrogen sulfide. The use of thiourea or guanidine instead of urea in the aforementioned process afforded pyrimido[4,5-d]pyrimidines 5c–5f. The condensation of 1 with thiourea gave [1,2,4]thiadiazolo[2,3-a]pyrimi-dine derivative 6. The reaction of 1 with benzaldehyde, followed by air oxidation, produced benzothiopyrano-pyrimidine 8, and condensation of the latter with urea or thiourea yielded [1,2,4]oxa(thia)diazolo[2,3-a]thio-chromeno[2,3-d]pyrimidinles. Bis-[1,2,4]triazolo[4,3-a]pyrimidines 12a and 12b were synthesized by the cyclocondensation of 1 with malonic and succinic acid dihydrazides. The newly synthesized fused pyrimidine derivatives were tested for their in vitro antiproliferative activity against two cell lines: human gastric carcinoma (BGC-823) and human lung cancer (A-549) in comparison to the NIH/3T3 murine fibroblast cell line. Some of these compounds, in particular 5a–5f, 6, 8, 10a, 10b, 12a, and 12b, proved to be the most effective against all cancer cell lines, with no impact on normal cells. Using the structure–activity relationships as a guide, the greater activity of compound 10b against A-549 cells (IC50 = 14.15±0.33 g/mL) was attributed to the presence of iminothiadiazolidine and thiopyran moieties. [ABSTRACT FROM AUTHOR] |
