| Abstract
| - In addition to our recent report on the potent anti-varicella-zoster virus (VZV) activity of someunusual bicyclic furopyrimidine nucleosides bearing long alkyl side chains, we herein reportthe further significant enhancement of the antiviral potency by inclusion of a phenyl group inthe side chain of these compounds. The target structures were prepared by the Pd-catalyzedcoupling of a series of para-substituted arylacetylenes with 5-iodo-2‘-deoxyuridine, to giveintermediate 5-alkynyl nucleosides which were cyclized in the presence of Cu to give the desiredbicyclic systems. The compounds display extraordinary potency and selectivity for VZV; themost active are ca. 10 000 times more potent than the reference compound acyclovir and ca.100 times more potent than the alkyl analogues earlier reported by us. The current compoundsshow little cytotoxicity, leading to selectivity index values ⩾ 1 000 000. From a range of DNAand RNA viruses tested, only VZV was inhibited by these compounds indicating their extremeselectivity for this target virus. The novelty of the molecules, coupled with their extreme potencyand selectivity, their desirable physicochemical properties, and their relative ease of synthesis,makes them of considerable interest for potential drug development for VZV infections.
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