title: SAR studies on a novel series of human cytomegalovirus primase inhibitors.
abstract: 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.
authors.affiliation: Amgen Inc., 1120 Veterans Boulevard ASF2-3, South San Francisco, CA 94080, USA. xiaoqic@amgen.com
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: J
authors.initials: J
authors.lastname: Adrian
authors.forename: T
authors.initials: T
authors.lastname: Cushing
authors.forename: H
authors.initials: H
authors.lastname: Dimaio
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: 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: 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
chemical_list: D000998:Antiviral Agents; D011743:Pyrimidines; D019915:DNA Primase