Synthesis and Antiviral Activity of Novel Acyclic Nucleoside Analogues of 5-(1-Azido-2-haloethyl)uracils

Abstract

We present the discovery of a novel category of 5-substituted acyclic pyrimidine nucleosides as potent antiviral agents. A series of 1-[(2-hydroxyethoxy)methyl] (5−7), 1-[(2-hydroxy-1-(hydroxymethyl)ethoxy)methyl] (8−10), and 1-[4-hydroxy-3-(hydroxymethyl)-1-butyl] (11−13) derivatives of 5-(1-azido-2-haloethyl)uracil were synthesized and evaluated for their biological activity in cell culture. 1-[4-Hydroxy-3-(hydroxymethyl)-1-butyl]-5-(1-azido-2-chloroethyl)uracil (12) was the most effective antiviral agent in the in vitro assays against DHBV (EC50 = 0.31−1.55 μM) and HCMV (EC50 = 3.1 μM). None of the compounds investigated showed any detectable toxicity to several stationary and proliferating host cells