SAR studies on a novel series of human cytomegalovirus primase inhibitors.
A novel series of imidazolylpyrimidines were found to possess inhibitory activity against the human CMV UL70 primase. Extensive SAR studies on an HTS lead led to potent, orally bioavailable compounds with anti-CMV IC(50) values of 150 nM in both viral yield and viral DNA replication assays and with a much reduced cytotoxicity compared to marketed treatments ganciclovir and cidofovir.
Chen
X
X
Amgen Inc., 1120 Veterans Boulevard ASF2-3, South San Francisco, CA 94080, USA. xiaoqic@amgen.com
Adrian
J
J
Cushing
T
T
Dimaio
H
H
Liang
L
L
Mayorga
V
V
Miao
S
S
Peterson
M G
MG
Powers
J P
JP
Spector
F
F
Stein
C
C
Wright
M
M
Xu
D
D
Ye
Q
Q
Jaen
J
J
D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D001682:Biological Availability; D003587:Cytomegalovirus / Q000187:drug effects* / Q000201:enzymology; D019915:DNA Primase / Q000037:antagonists & inhibitors*; D004261:DNA Replication; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D020128:Inhibitory Concentration 50; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D013329:Structure-Activity Relationship; D019562:Viral Load
D000998:Antiviral Agents; D011743:Pyrimidines; D019915:DNA Primase