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Bioorg Chem ; 38(6): 265-70, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20947122

ABSTRACT

A new class of inhibitors of herpes simplex virus replication was found. The compounds under study are derived from condensed 1,2,4-triazolo[5,1-c][1,2,4]triazines and 1,2,4-triazolo[1,5-a]pyrimidines, structural analogues of natural nucleic bases. Antiherpetic activity and cytotoxicity of the compounds were studied. The corresponding triphosphates of several active compounds were prepared and tested as inhibitors of DNA synthesis catalyzed by herpes simplex virus polymerase. The potential mechanism of their action is blocking of DNA dependent DNA polymerase, a key enzyme of viral replication.


Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Herpes Simplex/drug therapy , Herpesvirus 1, Human/drug effects , Triazines/chemistry , Triazines/pharmacology , Triazoles/chemistry , Triazoles/pharmacology , Animals , Cell Line , Cell Survival , Chlorocebus aethiops , DNA-Directed DNA Polymerase/metabolism , Herpesvirus 1, Human/enzymology , Humans , Models, Molecular , Nucleic Acid Synthesis Inhibitors , Polyphosphates/chemistry , Polyphosphates/pharmacology , Vero Cells , Virus Replication/drug effects
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