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- W154285872 abstract "Hydroxyurea (HU), a ribonucleotide reductase inhibitor has been used in the treatment of some malignant and viral diseases and seems now to be promising, in association with 2,3dideoxynucleosides, for the management of AIDS. In an attempt to increase the specificity of action of this radical scavenger, or at least, to study the topological aspects of its reactivity, we introduced the N-hydroxyureido group into nucleosides by using Mitsunobu reaction or by reacting a nucleoside nitrogen nucleophile with a carbonyl electrophile. From the currently available antiviral testing results, concerning the nucleoside analogues it appears that the most noticable activity exert against Varicella Zoster virus (VZV). One acyclonucleoside derivative was found to be very active against the virus HIV-1, its therapeutic index is better than 100.000. We prepared peptid-like dinucleotide analogues33,36 also in which the internucleosidic bridge consists of a spacer of approximately the same length as in the natural compounds. These compounds could be tested as inhibitors of nucleotide-protein interactions, we supposed that they are able to disrupt zinc finger parts of nucleocapsid. Antiviral activity of these dinucleotides were tested in vitro against HIV-1, HIV-2, HSV-1, HSV-2, CMV, VZV and EBV but in no case EC50 values inferior to 10 µM was found." @default.
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- W154285872 date "1996-01-01" @default.
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- W154285872 title "Nucleosides and acyclonucleosides bearing a N-hydroxyureido group" @default.
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