title: Indinavir analogues with blocked metabolism sites as HIV protease inhibitors with improved pharmacological profiles and high potency against PI-resistant viral strains.
abstract: Indinavir analogues with blocked metabolism sites show highly improved pharmacokinetic profiles in animals. The cis-aminochromanol substituted analogues exhibited excellent potency against both the wild-type (NL4-3) virus and protease inhibitor-resistant HIV strains.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. yuan_cheng@merck.com
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Fengqi
authors.initials: F
authors.lastname: Zhang
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Rano
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Lu
authors.forename: William A
authors.initials: WA
authors.lastname: Schleif
authors.forename: Lori
authors.initials: L
authors.lastname: Gabryelski
authors.forename: David B
authors.initials: DB
authors.lastname: Olsen
authors.forename: Mark
authors.initials: M
authors.lastname: Stahlhut
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Rutkowski
authors.forename: Jiunn H
authors.initials: JH
authors.lastname: Lin
authors.forename: Lixia
authors.initials: L
authors.lastname: Jin
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Emini
authors.forename: Kevin T
authors.initials: KT
authors.lastname: Chapman
authors.forename: James R
authors.initials: JR
authors.lastname: Tata
mesh_terms: D000818:Animals; D019540:Area Under Curve; D004285:Dogs; D004351:Drug Resistance; D006678:HIV / Q000187:drug effects*; D016333:HIV Protease / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D019469:Indinavir / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D020128:Inhibitory Concentration 50; D008657:Metabolic Clearance Rate; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir; D016333:HIV Protease