title: Nonpeptidic HIV protease inhibitors: 6-alkyl-5,6-dihydropyran-2-ones possessing a novel and achiral 3-(2-t-butyl-5-methyl-4-sulfamate)phenylthio moiety.
abstract: Dihydropyran-2-ones possessing a sulfamate moiety at the 4-position of the thiophenyl ring were designed to reach S3' pocket of the HIV protease. Synthetic routes for the preparation of thiotosylates possessing 3-(2-t-butyl-5-methyl-4-sulfamate) phenylthio moiety were established. SAR of various sulfamate analogs including HIV protease binding affinities, antiviral activities and therapeutic indices will be described.
authors.affiliation: Department of Chemistry, Parke-Davis Pharmaceutical Research, Ann Arbor, MI 48106, USA.
authors.forename: J V
authors.initials: JV
authors.lastname: Vara Prasad
authors.forename: L J
authors.initials: LJ
authors.lastname: Markoski
authors.forename: F E
authors.initials: FE
authors.lastname: Boyer
authors.forename: J M
authors.initials: JM
authors.lastname: Domagala
authors.forename: E L
authors.initials: EL
authors.lastname: Ellsworth
authors.forename: C
authors.initials: C
authors.lastname: Gajda
authors.forename: S E
authors.initials: SE
authors.lastname: Hagen
authors.forename: B D
authors.initials: BD
authors.lastname: Tait
authors.forename: E A
authors.initials: EA
authors.lastname: Lunney
authors.forename: P J
authors.initials: PJ
authors.lastname: Tummino
authors.forename: D
authors.initials: D
authors.lastname: Ferguson
authors.forename: T
authors.initials: T
authors.lastname: Holler
authors.forename: D
authors.initials: D
authors.lastname: Hupe
authors.forename: C
authors.initials: C
authors.lastname: Nouhan
authors.forename: S J
authors.initials: SJ
authors.lastname: Gracheck
authors.forename: S
authors.initials: S
authors.lastname: VanderRoest
authors.forename: J
authors.initials: J
authors.lastname: Saunders
authors.forename: K
authors.initials: K
authors.lastname: Iyer
authors.forename: M
authors.initials: M
authors.lastname: Sinz
mesh_terms: D000818:Animals; D004220:Disulfides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006678:HIV / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D008958:Models, Molecular; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004220:Disulfides; D017320:HIV Protease Inhibitors; C400303:PD 178390; D011753:Pyrones; D013451:Sulfonic Acids; C005741:sulfamic acid