Discovery of a novel series of inhibitors of human cytomegalovirus primase.
Infection by human cytomegalovirus (hCMV) remains a potent threat to susceptible people throughout the world. We have discovered a series of imidazolyl-pyrimidine compounds, which were found to be irreversible inhibitors of the hCMV UL70 primase based on results from radiolabeling and SAR studies. Two promising analogs are described that rival ganciclovir and cidofovir in antiviral potency and possess improved cytotoxicity profiles.
Cushing
T D
TD
Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. tcushing@amgen.com
Adrian
J
J
Chen
X
X
DiMaio
H
H
Doughan
B
B
Flygare
J
J
Liang
L
L
Mayorga
V
V
Miao
S
S
Mellon
H
H
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
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects; D002460:Cell Line; D003587:Cytomegalovirus / Q000187:drug effects* / Q000201:enzymology*; D019915:DNA Primase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D011743:Pyrimidines; D019915:DNA Primase; C030986:pyrimidine