title: 8-Hydroxy-3,4-dihydropyrrolo[1,2-a]pyrazine-1(2H)-one HIV-1 integrase inhibitors.
abstract: A series of potent novel 8-hydroxy-3,4-dihydropyrrolo[1,2-a]pyrazine-1(2H)-one HIV-1 integrase inhibitors was identified. These compounds inhibited the strand transfer process of HIV-1 integrase and viral replication in cells. Compound 12 is active against replication of HIV-1 in cell culture with a CIC(95) of 0.31microM. Further SAR exploration led to the preparation of pseudosymmetrical tricyclic pyrrolopyrazine inhibitors 23 and 24 with further improvement in antiviral activity.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. thor_fisher@merck.com
authors.forename: Thorsten E
authors.initials: TE
authors.lastname: Fisher
authors.forename: Boyoung
authors.initials: B
authors.lastname: Kim
authors.forename: Donnette D
authors.initials: DD
authors.lastname: Staas
authors.forename: Terry A
authors.initials: TA
authors.lastname: Lyle
authors.forename: Steven D
authors.initials: SD
authors.lastname: Young
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Vacca
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Zrada
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: M Reza
authors.initials: MR
authors.lastname: Anari
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Kochansky
authors.forename: John S
authors.initials: JS
authors.lastname: Wai
mesh_terms: D045744:Cell Line, Tumor; D019427:HIV Integrase / Q000502:physiology; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D011719:Pyrazines / Q000737:chemistry* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000821:virology
chemical_list: D019428:HIV Integrase Inhibitors; D011719:Pyrazines; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1