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Syntheses and biological evaluation of C-5 hydroxyethyl N-acyclic pyrimidine nucleoside analogs

Syntheses of 5-(2-hydroxyethyl)uracil derivatives (3-10) and uracil derivatives bearing acyclovir- like (11, 12 and 14) and 2, 3-dihydroxypropyl chain at N-1 (15 and 16) are described. Furthermore, a number of pyrimidine and purine nucleoside analogues in which the sugar residues have been replaced by acyclic side-chains have been found to exhibit high antiviral activity. The target pyrimidine acyclic nucleoside analogs 12 and 16 were prepared for potential application as suitable agents for monitoring gene expression using positron emission tomography (PET). The syntheses of compounds 12 and 16 were conducted in four parts: (i) the synthesis of key 5-(2- hydroxyethyl)uracil (3) ; (ii) the synthesis of derivatives 9 and 10 suitable for regiospecific N- alkylation ; (iii) an introduction of acyclovir- like and 2, 3-dihydroxypropyl side chain at position N-1 of pyrimidine, and (iv) removal of protecting groups to obtain the target compounds 12 and 16. Cytostatic evaluations of compounds 3- 12 and 14-16 against human malignant tumor cell lines will be also presented.

pyrimidine acyclic nucleosides; 1H and 13C NMR spectroscopy

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