DERIVATIVES OF Y-2-FLUORO-BETA-D-ARABINOFURANOSYL)-5-PHENYLURACIL AND5-BENZYLURACIL - SYNTHESIS AND BIOLOGICAL PROPERTIES

A number of 1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil and -cy tosine nucleosides substituted at the 5 position with a nitrophenyl or nitrobenzyl group were synthesized from 5-phenyl- and 5-benzyluracil via condensation of the fluorinated sugar, followed by nitration. The corresponding amino analogues were also prepared by reduction of the n itro nucleosides. The uracil nucleosides were converted into the corre sponding cytosine nucleosides by way of the triazole intermediates. No ne of these nucleosides exhibited significant activity against herpes simplex virus type 1 in Vero cells. However, cytosine nucleosides cont aining the o-nitrophenyl, p-nitrophenyl, p-nitrobenzyl or p-aminobenzy l substituent were found to be toxic (even at 1 mu M) to uninfected Ve ro cells, although they were essentially nontoxic in HL-60 cells. The 5'-monophosphates of the uracil nucleosides were inhibitors of the rea ction catalyzed by purified Ehrlich ascites carcinoma thymidylate synt hase, the 5-phenyluracil nucleotides causing a strong inhibition, comp etitive vs dUMP, described by the K-i value of 0.01 mu M.