title: Dihydroxypyridopyrazine-1,6-dione HIV-1 integrase inhibitors.
abstract: A series of potent novel dihydroxypyridopyrazine-1,6-dione HIV-1 integrase inhibitors was identified. These compounds inhibited the strand transfer process of HIV-1 integrase and viral replication in cells. Compound 6 is active against replication of HIV with a CIC(95) of 0.31 microM and exhibits no shift in potency in the presence of 50% normal human serum. It displays a good pharmacokinetic profile when dosed in rats and no covalent binding with microsomal proteins in both in vitro and in vivo models.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. john_wai@merck.com
authors.forename: John S
authors.initials: JS
authors.lastname: Wai
authors.forename: Boyoung
authors.initials: B
authors.lastname: Kim
authors.forename: Thorsten E
authors.initials: TE
authors.lastname: Fisher
authors.forename: Linghang
authors.initials: L
authors.lastname: Zhuang
authors.forename: Mark W
authors.initials: MW
authors.lastname: Embrey
authors.forename: Peter D
authors.initials: PD
authors.lastname: Williams
authors.forename: Donnette D
authors.initials: DD
authors.lastname: Staas
authors.forename: Chris
authors.initials: C
authors.lastname: Culberson
authors.forename: Terry A
authors.initials: TA
authors.lastname: Lyle
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Vacca
authors.forename: Daria J
authors.initials: DJ
authors.lastname: Hazuda
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Felock
authors.forename: William A
authors.initials: WA
authors.lastname: Schleif
authors.forename: Lori J
authors.initials: LJ
authors.lastname: Gabryelski
authors.forename: Lixia
authors.initials: L
authors.lastname: Jin
authors.forename: I-Wu
authors.initials: IW
authors.lastname: Chen
authors.forename: Joan D
authors.initials: JD
authors.lastname: Ellis
authors.forename: Rama
authors.initials: R
authors.lastname: Mallai
authors.forename: Steven D
authors.initials: SD
authors.lastname: Young
mesh_terms: D000818:Animals; D001554:Benzene / Q000737:chemistry; D002460:Cell Line; D006678:HIV / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008862:Microsomes, Liver / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects