brivudine and 5-vinyl-2--deoxyuridine

The problems encountered in the synthesis of 5-vinyl-2'-deoxyuridine are outlined and the synthesis of 5-bromoethynyl-2'-deoxyuridine described. E-5-(2-Bromovinyl)-2'-deoxyuridine is the most potent and specific agent against some herpes viruses yet discovered; we have now synthesised the Z-isomer and this appears to be essentially biologically inert.

Topics: Animals; Antiviral Agents; Bromodeoxyuridine; Deoxyuridine; Drug Evaluation, Preclinical; Herpesviridae; Structure-Activity Relationship; Uracil

The chemical syntheses of some 5-substituted uracil deorivatives, in particular 5-vinyl-2'-deoxyuridine, 5-ethynyl-2'-deoxyuridine and 4-(2-bromovinyl)-2'-deoxy-uridine are reviewed and their potential as radiation sensitizing agents, anti-cancer agents and antiviral agents is discussed. 5-Ethynyl-2'-deoxyuridine is not incorporated into DNA; is a thymidylate synthetase inhibitor and has a possible use as an anti-cancer drug. 5-Vinyl-2'-dexyuridine can replace thymidine residues in DNA of phage T3; does not cause the organism to be significantly more sensitive to gamma-radiation but its presence in DNA causes the organisms to be significantly more sensitive to gamma-radiation but its presence in DNA causes the organism to lose viability, possibly through chemical cross-linking reactions of the vinyl group. 5-(2-Bromovinyl)-2'-deoxyuridine is the most specific and potent antiherpes compound yet known. Its mode of action and its affects on herpes virus in vitro and in vivo with animal models and clinical observations are described.

Topics: Bromodeoxyuridine; Chemical Phenomena; Chemistry; Coliphages; Deoxyuridine; DNA, Bacterial; DNA, Viral; Escherichia coli; Methods; Mycoplasma; Uracil