1,2,4-Triazoloazine derivatives as a new type of herpes simplex virus inhibitors.
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.
Deev
S L
SL
Postovsky Institute of Organic Synthesis, Ekaterinburg, Russia.
Yasko
M V
MV
Karpenko
I L
IL
Korovina
A N
AN
Khandazhinskaya
A L
AL
Andronova
V L
VL
Galegov
G A
GA
Shestakova
T S
TS
Ulomskii
E N
EN
Rusinov
V L
VL
Chupakhin
O N
ON
Kukhanova
M K
MK
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival; D002522:Chlorocebus aethiops; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006561:Herpes Simplex / Q000188:drug therapy*; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008958:Models, Molecular; D019384:Nucleic Acid Synthesis Inhibitors; D011122:Polyphosphates / Q000737:chemistry / Q000494:pharmacology; D014227:Triazines / Q000737:chemistry* / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology*; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D019384:Nucleic Acid Synthesis Inhibitors; D011122:Polyphosphates; D014227:Triazines; D014230:Triazoles; D004259:DNA-Directed DNA Polymerase