Nucleoside analogues. 4. Molecular combinations of anti-tumour drugs: synthesis of 5-fluorouracil seco-nucleosides with N-(2-chloroethyl)-N-nitrosourea residues by using aryl N-nitrosocarbamates.
1986
: The biological study of molecular combination of anti-tumour drugs remains unexplored. Some drugs prepared earlier, seco-nucleosides with 5-fluorouracil as base and incorporating a N-(2-chloroethyl)-N-nitrosourea (CNU) residue in the linear 'sugar' moiety, have now been obtained much more readily by using aryl N-nitrosocarbamates. These include the more reactive S-oxide of the original combination, B 3839. The structure of a compound with the CNU in the 'alcohol' arm of the seco-nucleoside has been clarified. Isomeric combinations having hydroxyl groups in either the 'alcohol' or the 'aldehyde' arm, with different hydrolysis rates, have been synthesized. Results of anti-tumour testing are reported in the proceeding paper.
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