title: Oximinoarylsulfonamides as potent HIV protease inhibitors.
abstract: The need for a potent HIV protease inhibitor (PI) to combat emerging PI-resistant viruses is anticipated. Analogs formulated from the combination of structural fragments of Ritonavir, Lopinavir, and Amprenavir were synthesized. Analogs containing the oxime pharmacophore were found to have improved activities against both wild type and resistant (A17) viruses. The synthesis and structure-activity relationships (SAR) based upon the in vitro IC50 of this series of compounds are reported.
authors.affiliation: Abbott Laboratories, GPRD, D-47D, Building AP52N, 200 Abbott Park Road, Abbott Park, IL 60064-3501, USA. clinton.yeung@abbott.com
authors.forename: Clinton M
authors.initials: CM
authors.lastname: Yeung
authors.forename: Larry L
authors.initials: LL
authors.lastname: Klein
authors.forename: Charles A
authors.initials: CA
authors.lastname: Flentge
authors.forename: John T
authors.initials: JT
authors.lastname: Randolph
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.forename: MingHua
authors.initials: M
authors.lastname: Sun
authors.forename: Tatyana
authors.initials: T
authors.lastname: Dekhtyar
authors.forename: Vincent S
authors.initials: VS
authors.lastname: Stoll
authors.forename: Dale J
authors.initials: DJ
authors.lastname: Kempf
mesh_terms: D001665:Binding Sites; D002219:Carbamates; D015195:Drug Design; D005663:Furans; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007700:Kinetics; D061466:Lopinavir; D008958:Models, Molecular; D008968:Molecular Conformation; D011744:Pyrimidinones / Q000737:chemistry; D019438:Ritonavir / Q000737:chemistry; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D013449:Sulfonamides; D061466:Lopinavir; C095108:amprenavir; D016333:HIV Protease; D019438:Ritonavir