title: Discovery of a novel series of inhibitors of human cytomegalovirus primase.
abstract: 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.
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard, South San Francisco, CA 94080, USA. tcushing@amgen.com
authors.forename: T D
authors.initials: TD
authors.lastname: Cushing
authors.forename: J
authors.initials: J
authors.lastname: Adrian
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: H
authors.initials: H
authors.lastname: DiMaio
authors.forename: B
authors.initials: B
authors.lastname: Doughan
authors.forename: J
authors.initials: J
authors.lastname: Flygare
authors.forename: L
authors.initials: L
authors.lastname: Liang
authors.forename: V
authors.initials: V
authors.lastname: Mayorga
authors.forename: S
authors.initials: S
authors.lastname: Miao
authors.forename: H
authors.initials: H
authors.lastname: Mellon
authors.forename: M G
authors.initials: MG
authors.lastname: Peterson
authors.forename: J P
authors.initials: JP
authors.lastname: Powers
authors.forename: F
authors.initials: F
authors.lastname: Spector
authors.forename: C
authors.initials: C
authors.lastname: Stein
authors.forename: M
authors.initials: M
authors.lastname: Wright
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.forename: Q
authors.initials: Q
authors.lastname: Ye
authors.forename: J
authors.initials: J
authors.lastname: Jaen
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D011743:Pyrimidines; D019915:DNA Primase; C030986:pyrimidine