title: Ultra-potent P1 modified arylsulfonamide HIV protease inhibitors: the discovery of GW0385.
abstract: A novel series of P1 modified HIV protease inhibitors was synthesized and evaluated for in vitro antiviral activity against wild-type virus and protease inhibitor-resistant viruses. Optimization of the P1 moiety resulted in compounds with femtomolar enzyme activities and cellular antiviral activities in the low nanomolar range culminating in the identification of clinical candidate GW0385.
authors.affiliation: GlaxoSmithKline, 5 Moore Drive, Research Triangle Park, NC 27709, USA. john.6.miller@gsk.com
authors.forename: John F
authors.initials: JF
authors.lastname: Miller
authors.forename: C Webster
authors.initials: CW
authors.lastname: Andrews
authors.forename: Michael
authors.initials: M
authors.lastname: Brieger
authors.forename: Eric S
authors.initials: ES
authors.lastname: Furfine
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hale
authors.forename: Mary H
authors.initials: MH
authors.lastname: Hanlon
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hazen
authors.forename: Istvan
authors.initials: I
authors.lastname: Kaldor
authors.forename: Ed W
authors.initials: EW
authors.lastname: McLean
authors.forename: David
authors.initials: D
authors.lastname: Reynolds
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Sammond
authors.forename: Andrew
authors.initials: A
authors.lastname: Spaltenstein
authors.forename: Roger
authors.initials: R
authors.lastname: Tung
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Turner
authors.forename: Robert X
authors.initials: RX
authors.lastname: Xu
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Sherrill
mesh_terms: D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C494906:GW0385; D017320:HIV Protease Inhibitors; D013449:Sulfonamides