Synthesis and anti-herpes virus activity of 2'-deoxy-4'-thiopyrimidine nucleosides.
A series of 5-substituted 2'-deoxy-4'-thiopyrimidine nucleosides was synthesized and evaluated as potential antiviral agents. A number of analogues such as 2'-deoxy-5-propyl-4'-thiouridine (3ii), 2'-deoxy-5-isopropyl-4'-thiouridine (3iii), 5-cyclopropyl-2'-deoxy-4'-thiouridine (3iv), 2'-deoxy-4'-thio-5-vinyluridine (3viii), and 5-(2-chloroethyl)-2'-deoxy-4'-thiouridine (3xx) were found to be highly active against herpes simplex virus type-1 (HSV-1) and varicella zoster virus (VZV) in vitro with no significant cytotoxicity. The compound with the broadest spectrum of activity was 2'-deoxy-5-ethyl-4'-thiouridine (3i) which showed significant activity against HSV-1, HSV-2, and VZV.
Rahim
S G
SG
Wellcome Research Laboratories, Beckenham, Kent, U.K.
Trivedi
N
N
Bogunovic-Batchelor
M V
MV
Hardy
G W
GW
Mills
G
G
Selway
J W
JW
Snowden
W
W
Littler
E
E
Coe
P L
PL
Basnak
I
I
Whale
R F
RF
Walker
R T
RT
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D006801:Humans; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology*; D018139:Simplexvirus / Q000187:drug effects*; D014709:Vero Cells; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D011741:Pyrimidine Nucleosides