Nucleoside analogues as highly potent and selective inhibitors of herpes simplex virus thymidine kinase.
A series of carboxamide derivatives of 5'-amino-2',5'-dideoxy-5-ethyluridine has been prepared as inhibitors of HSV-TK (herpes simplex virus thymidine kinase). The most potent compounds were derived from xanthene, thioxanthene and dihydroanthracene carboxylic acids. The lead compounds show subnanomolar IC(50) values against HSV TKs.
Martin
J A
JA
Department of Medicinal Chemistry, Roche Discovery Welwyn, Broadwater Road, Welwyn Garden City, AL7 3AY, Herts, UK. joseph.martin@roche.com
Lambert
R W
RW
Merrett
J H
JH
Parkes
K E
KE
Thomas
G J
GJ
Baker
S J
SJ
Bushnell
D J
DJ
Cansfield
J E
JE
Dunsdon
S J
SJ
Freeman
A C
AC
Hopkins
R A
RA
Johns
I R
IR
Keech
E
E
Simmonite
H
H
Walmsley
A
A
Wong Kai-In
P
P
Holland
M
M
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D018139:Simplexvirus / Q000201:enzymology*; D013937:Thymidine Kinase / Q000037:antagonists & inhibitors*; D014529:Uridine / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*
C434644:5'-amino-2',5'-dideoxy-5-ethyluridine; D004791:Enzyme Inhibitors; D013937:Thymidine Kinase; D014529:Uridine