Collect. Czech. Chem. Commun. 1984, 49, 2541-2550

Preparation and biological effects of N-tris(hydroxymethyl)methylaminocarbonylmethyl derivatives of heterocyclic bases

Helmut Pischela, Antonín Holýb, Jiří Veselýb and Günther Wagnera

a Sektion Biowissenschaften-Pharmazie, Karl-Marx-Universität, Leipzig, German Democratic Republic
b Institute of Organic Chemistry and Biochemistry, Czechoslovak Academy of Sciences, 166 10 Prague 6, Czechoslovakia


The title compounds were synthetized by the reaction of TRIS with p-nitrophenyl or alkyl esters of N-carboxymethyl derivatives of uracil, 5-chloro-, 5-bromo-, 5-iodouracil, thymine, cytosine, 6-azauracil, 2-pyridone, 2-pyrimidone, 3-pyridazone and orotic acid. The following novel N-carboxymethyl derivatives are also described: 6-azauracil derivative VIIa by condensation of 4-thio-6-azauracil with methyl bromoacetate followed by hydrolysis, 5-chloruracil derivative IIIa by chlorination of uracil compound IIa, 2-pyrimidone (IXa) and 3-pyridazone derivative Xa by the reaction of the sodium salts of the bases with sodium chloracetate. Of all the amides tested, only the 3-pyridazone derivative Xd and orotic acid derivative XIId inhibited the growth of L-1210 mouse leukemic cells in vitro with 1D50 approx. 10-4 mol l-1.