title: Novel arylsulfonamides possessing sub-picomolar HIV protease activities and potent anti-HIV activity against wild-type and drug-resistant viral strains.
abstract: A novel series of P1' chain-extended arylsufonamides was synthesized and evaluated for wild-type HIV protease inhibitory activity and in vitro antiviral activity against wild type virus and two protease inhibitor-resistant mutant viruses. All of the compounds showed dramatic increases in enzyme activity as compared to the currently marketed HIV protease inhibitors amprenavir, indinavir, and nelfinavir. In addition, significant improvements in antiviral potencies against wild type and the two mutant viruses were also realized.
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: Eric S
authors.initials: ES
authors.lastname: Furfine
authors.forename: Mary H
authors.initials: MH
authors.lastname: Hanlon
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hazen
authors.forename: John A
authors.initials: JA
authors.lastname: Ray
authors.forename: Laurence
authors.initials: L
authors.lastname: Robinson
authors.forename: Vicente
authors.initials: V
authors.lastname: Samano
authors.forename: Andrew
authors.initials: A
authors.lastname: Spaltenstein
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D024921:Drug Resistance, Multiple, Viral / Q000187:drug effects / Q000235:genetics*; D006678:HIV / Q000187:drug effects / Q000235:genetics*; D016333:HIV Protease / Q000187:drug effects* / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D009154:Mutation; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; D016333:HIV Protease