Synthesis and Antitumor Activity of New Pyrimidine and Caffeine Derivatives
Ameen Ali Abu-Hashem,
Hoda Abdel Raouf Hussein.
6-Amino-1, 3-dimethyl-1H-pyrimidine-2, 4-dione 2 was prepared by alkylation of 6-amino-
1H-pyrimidine-2, 4-dione 1 with methyl iodide. Formylation of 2 with formic acid afforded N-(1, 3-
dimethyl-dioxo-tetrahydropyrimidin-4-yl)-formamide 3. The nitration of 3 gave N - (1,3-dimethyl-5-
nitro-dioxo-tetrahydropyrimidin-4-yl) formamide 4. Reduction of 4 by zinc dust in glacial acetic acid
yielded dimethyl-dihydro-purine-2, 6-dione 5. Addition of bromine to 2 leads to the formation of 6-
amino-5-bromo-dimethyl-pyrimidine-2, 4-dione 7, cycloaddition of 7 with formamide afford the same
product (theophylline 5), alkylated of 5 with methyl iodide to give caffeine 6. Reaction of 7 with glycine
gave 2-(6-amino-dimethyl-dioxo-tetrahydropyrimidin-5-ylamino) acetic acid 8, refluxing of 8 with acetic acid
/methanol gave dimethyl-dihydropyrimidopyrazine-trione 9, alkylation of 9 with alkyliodide afforded tetra-alkyldihydropyrimidopyrazine-
trione 10a and 10b. The Cytotoxicity screen of the synthesized compounds was evaluated and
the result showed that 10a, 10b, 9, 8, 7 and 6 exhibited highly potential antitumor activity.
Keywords: Alkylation, antitumor, caffeine, cytotoxicity, pyrimidine, reduction.
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