title: Naphthyridinone (NTD) integrase inhibitors 4. Investigating N1 acetamide substituent effects with C3 amide groups.
abstract: A series of N1 acetamide substituted naphthyridinone HIV-1 integrase inhibitors have been explored to understand structure-activity relationships (SAR) with various C3 amide groups. Investigations were evaluated using integrase enzyme inhibition, antiviral activity and protein binding effects to optimize the sub-structures. Lipophilicity was also incorporated to understand ligand lipophilic efficiency as a function of the structural modifications. Three representative analogs were further examined in a peripheral blood mononuclear cell (PBMC) antiviral assay as well as in vitro and in vivo drug metabolism and pharmacokinetic studies.
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapy Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, USA. Electronic address: brian.a.johns@gsk.com.
authors.forename: Brian A
authors.initials: BA
authors.lastname: Johns
authors.affiliation: Shionogi Pharmaceutical Research Center, Shionogi & Co., Ltd, 3-1-1, Futaba-cho, Toyonaka-shi, Osaka 561-0825, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawasuji
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapy Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Weatherhead
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapy Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Eric E
authors.initials: EE
authors.lastname: Boros
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapy Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Thompson
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapy Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Cecilia S
authors.initials: CS
authors.lastname: Koble
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapy Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Edward P
authors.initials: EP
authors.lastname: Garvey
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapy Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Foster
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapy Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Jeffrey
authors.affiliation: Shionogi Pharmaceutical Research Center, Shionogi & Co., Ltd, 3-1-1, Futaba-cho, Toyonaka-shi, Osaka 561-0825, Japan.
authors.forename: Tamio
authors.initials: T
authors.lastname: Fujiwara
mesh_terms: D000081:Acetamides / Q000737:chemistry*; D000577:Amides / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D015394:Molecular Structure; D009287:Naphthyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000081:Acetamides; D000577:Amides; D019428:HIV Integrase Inhibitors; D009287:Naphthyridines; D019427:HIV Integrase
keywords: HIV-1; Integrase; Naphthyridinone