title: Naphthyridinone (NTD) integrase inhibitors: N1 protio and methyl combination substituent effects with C3 amide groups.
abstract: Substituent effects of a series of N1 protio and methyl naphthyridinone HIV-1 integrase strand-transfer inhibitors has been explored. The effects of combinations of the N1 substituent and C3 amide groups was extensively studied to compare enzyme inhibition, antiviral activity and protein binding effects on potency. The impact of substitution on ligand efficiency was considered and several compounds were advanced into in vivo pharmacokinetic studies ultimately leading to the clinical candidate GSK364735.
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapy Area Unit, Five Moore Drive, Research Triangle Park, NC 27709, USA. brian.a.johns@gsk.com
authors.forename: Brian A
authors.initials: BA
authors.lastname: Johns
authors.forename: Takashi
authors.initials: T
authors.lastname: Kawasuji
authors.forename: Jason G
authors.initials: JG
authors.lastname: Weatherhead
authors.forename: Eric E
authors.initials: EE
authors.lastname: Boros
authors.forename: James B
authors.initials: JB
authors.lastname: Thompson
authors.forename: Cecilia S
authors.initials: CS
authors.lastname: Koble
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: Tamio
authors.initials: T
authors.lastname: Fujiwara
mesh_terms: D000577:Amides / Q000737:chemistry*; D001681:Biological Assay; D004789:Enzyme Activation / Q000187:drug effects; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009287:Naphthyridines / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D019428:HIV Integrase Inhibitors; D009287:Naphthyridines; C581958:GSK364735