title: 1,3,4-Oxadiazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 2: SAR of the C5 position.
abstract: The use of a 1,3,4-oxadiazole in combination with an 8-hydroxy-1,6-naphthyridine ring system has been shown to deliver potent enzyme and antiviral activity through inhibition of viral DNA integration. This report presents a detailed structure-activity investigation of the C5 position resulting in low nM potency for several analogs with an excellent therapeutic index.
authors.affiliation: Department of Medicinal Chemistry, Infectious Diseases Center for Excellence in Drug Discovery, GlaxoSmithKline Research & Development, Five Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Johns
authors.forename: Jason G
authors.initials: JG
authors.lastname: Weatherhead
authors.forename: Scott H
authors.initials: SH
authors.lastname: Allen
authors.forename: James B
authors.initials: JB
authors.lastname: Thompson
authors.forename: Edward P
authors.initials: EP
authors.lastname: Garvey
authors.forename: Scott A
authors.initials: SA
authors.lastname: Foster
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Jeffrey
authors.forename: Wayne H
authors.initials: WH
authors.lastname: Miller
mesh_terms: D020816:Amino Acid Motifs; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D015658:HIV Infections / Q000188:drug therapy; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008670:Metals / Q000737:chemistry; D008956:Models, Chemical; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D010069:Oxadiazoles / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry*
chemical_list: D019380:Anti-HIV Agents; D002614:Chelating Agents; D019428:HIV Integrase Inhibitors; D008670:Metals; D009287:Naphthyridines; D010069:Oxadiazoles; D014230:Triazoles