Pyrimidines. Part II: Synthesis of novel pyrimidines, 1,2,4-triazolo[4,3-a]pyrimidin-7-ones and pyrimidino[2,1-c][1,2,4]triazin-8-ones for their antimicrobial and anticancer activities.

Abstract

Five main classes of novel pyrimidine derivatives have been synthesized; namely 6-substituted phenyl-5-cyano-3-methyl-2-phenacylhydrazino-3,4-dihydropyrimidin-4-ones 4a-e; 6-substituted phenyl-2-arylidene hydra-zino-5-cyano-3-methyl-3,4-dihydropyrimidin-4-ones 5a-i; 6-substituted phenyl-2-acylhydrazino-5-cyano-3-methyl-3,4-dihydropyrimidin-4-ones 7a-d, 8a-e and 9a-c; three novel series of 1,2,4-triazolo[4,3-a] pyrimidones 10a,b, 11a-d and 12a-d and 6-substituted phenyl-7-cyano-9-methyl-3-phenyl or 4-chlorophenyl-4,9-dihydropyrimido[2,1-c][1,2,4] triazin-8-ones 13a-c. Besides, the azide compound 2-azido-5-cyano-3-methyl-6-phenyl-3,4-dihydropyrimidin-4-one 6 was also synthesized. The prepared compounds were tested for antimicrobial and anticancer activity. Compounds 4b and 4d showed promising activity against Escherichia coli. Compounds 3c, 5c, 5e, 5g and 7b were active in the three cell line antitumor one dose primary assay and were evaluated in the 60 human tumor full panel cell line invitro screening. Compound 5c showed promising activity against all types of leukemia especially leukemia K-562 and leukemia SR with GI50 = 1.61 and 2.63 mmol/l respectively.