title: Nonpeptidic HIV protease inhibitors: 6-alkyl-5,6-dihydropyran-2-ones possessing achiral 3-(4-amino/carboxamide-2-t-butyl,5-methylphenyl thio) moiety: antiviral activities and pharmacokinetic properties.
abstract: Dihydropyran-2-ones possessing amino and carboxamide functionalities on 3-SPh (2-tert-butyl, 5-methyl) ring were synthesized and evaluated for their antiviral activities. Both the enantiomers of inhibitor 15 were synthesized. The in vitro resistance profile, inhibitory activities against cytochrome P450 isozymes and pharmacokinetic properties of inhibitor 15S will be discussed.
authors.affiliation: Department of Chemistry, Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Company, Ann Arbor, MI 48106, USA.
authors.forename: J V
authors.initials: JV
authors.lastname: Vara Prasad
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: L J
authors.initials: LJ
authors.lastname: Markoski
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
authors.forename: J
authors.initials: J
authors.lastname: Brodfuehrer
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004285:Dogs; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D051379:Mice; D008958:Models, Molecular; D011714:Pyrans / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D011714:Pyrans