title: A combinatorial library of indinavir analogues and its in vitro and in vivo studies.
abstract: A combinatorial library of 300HIV protease inhibitors has been synthesized. The library was screened against recombinant wild-type and mutant HIV-1 protease enzymes. The pharmacokinetics of the library was evaluated by dosing in dogs. Compounds that are notably more potent than indinavir and have favorable pharmacokinetic properties were identified.
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: Thomas A
authors.initials: TA
authors.lastname: Rano
authors.forename: Tracy T
authors.initials: TT
authors.lastname: Huening
authors.forename: Fengqi
authors.initials: F
authors.lastname: Zhang
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: Lawrence C
authors.initials: LC
authors.lastname: Kuo
authors.forename: Jiunn H
authors.initials: JH
authors.lastname: Lin
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.forename: Lixia
authors.initials: L
authors.lastname: Jin
authors.forename: Timothy V
authors.initials: TV
authors.lastname: Olah
authors.forename: Debra A
authors.initials: DA
authors.lastname: McLoughlin
authors.forename: Rick C
authors.initials: RC
authors.lastname: King
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; D020650:Combinatorial Chemistry Techniques; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000254:growth & development; D006801:Humans; D019469:Indinavir / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008657:Metabolic Clearance Rate; D009154:Mutation; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D017320:HIV Protease Inhibitors; D019469:Indinavir