title: The use of oxadiazole and triazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 1: Establishing the pharmacophore.
abstract: A series of HIV-1 integrase inhibitors containing a novel metal binding motif consisting of the 8-hydroxy-1,6-naphthyridine core and either an oxadiazole or triazole has been identified. The design of the key structural components was based on a two-metal coordination pharmacophore. This report presents initial structure-activity data that shows the new chelation architecture delivers potent inhibition in both enzymatic and antiviral assays.
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; 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*; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D002614:Chelating Agents; D019428:HIV Integrase Inhibitors; D009287:Naphthyridines; D010069:Oxadiazoles; D014230:Triazoles