Collect. Czech. Chem. Commun. 1982, 47, 2806-2813

Synthesis and biological activity of N-substituted 5-fluorouracil-1-acetamides

Helmut Pischela, Antonín Holýb, Jiří Veselýb, Günther Wagnera and Dieter Cechc

a Sektion Biowissenschaften-Pharmazie, Karl-Marx-Universitat, Leipzig, G.D.R.
b Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, 166 10 Prague 6, Czechoslovakia
c Sektion Chemie, Humboldt Universitat, Berlin, G.D.R.


Reaction of 5-fluorouracil (I) with sodium chloroacetate in the presence of sodium hydride afforded a mixture of 5-fluorouracil-1-acetic acid (II) and 5-fluorouracil-3-acetic acid (III). p-Nitrophenyl 5-fluorouracil-1-acetate (IV) reacted with amines in methanol or dimethylformamide to give N-substituted 5-fluorouracil-1-acetamides V. The following amides were prepared: diethylamide Vc, n-hexylamide Vd, cyclohexylamide Ve, adamantylamide Vf, anilide Vg, benzylamide Vh, benzhydrylamide Vi, pyrrolidide Vj, piperidide Vk, morpholide Vl, 3-dimethylaminopropylamide Vm, 3-aminopropylamide Vn, 2-hydroxyethylamide Vo, bis(2-hydroxyethyl)amide Vp and tris(hydroxymethyl)methylamide Vq. Compounds Vc-Vq do not inhibit the growth of Escherichia coli in concentrations up to 1 mg/ml. Compounds Vf and Vh have a weak, compound Vq a significant, inhibition effect on the growth of L-1210 mouse leukemic cells in vitro in concentrations 1.5 . 10-5 mol l-1.