title: Combining symmetry elements results in potent naphthyridinone (NTD) HIV-1 integrase inhibitors.
abstract: A series of naphthyridinone HIV-1 integrase strand-transfer inhibitors have been designed based on a psdeudo-C2 symmetry element present in the two-metal chelation pharmacophore. A combination of two distinct inhibitor binding modes resulted in potent inhibition of the integrase strand-transfer reaction in the low nM range. Effects of aryl and N1 substitutions are disclosed including the impact on protein binding adjusted antiviral activity.
authors.affiliation: GlaxoSmithKline Research & Development, Infectious Diseases Therapeutic 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: 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
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Kurose
authors.forename: Kenichi
authors.initials: K
authors.lastname: Matsumura
authors.forename: Tamio
authors.initials: T
authors.lastname: Fujiwara
mesh_terms: D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1; D009287:Naphthyridines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019428:HIV Integrase Inhibitors; D009287:Naphthyridines