Document 0032
 DOCN  M9460032
 TI    L-735,524: an orally bioavailable human immunodeficiency virus type 1
       protease inhibitor.
 DT    9408
 AU    Vacca JP; Dorsey BD; Schleif WA; Levin RB; McDaniel SL; Darke PL; Zugay
       J; Quintero JC; Blahy OM; Roth E; et al; Department of Medicinal
       Chemistry, Merck Research Laboratories,; West Point, PA 19486.
 SO    Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):4096-100. Unique Identifier
       : AIDSLINE MED/94224890
 AB    To date, numerous inhibitors of the human immunodeficiency virus type 1
       protease have been reported, but few have been studied extensively in
       humans, primarily as a consequence of poor oral bioavailability in
       animal models. L-735,524 represents a class of human immunodeficiency
       virus type 1 protease inhibitors, termed hydroxyaminopentane amides,
       that incorporate a basic amine into the hydroxyethylene inhibitor
       backbone. L-735,524 is a potent inhibitor of virus replication in cell
       culture and inhibits the protease-mediated cleavage of the viral
       precursor polyproteins that results in the production of noninfectious
       progeny viral particles. The compound is effective against viruses
       resistant to reverse transcriptase inhibitors and is synergistically
       active when used in combination with reverse transcriptase inhibitors.
       Most importantly, L-735,524 exhibits good oral bioavailability and
       plasma pharmacokinetic profiles in two species of laboratory animals by
       using clinically acceptable formulations. Accordingly, the compound was
       selected for evaluation of safety and pharmacokinetic studies in humans.
 DE    Administration, Oral  Animal  Antiviral Agents/*ADMINISTRATION &
       DOSAGE/PHARMACOKINETICS  Biological Availability  Blood
       Proteins/METABOLISM  Cell Line  Dogs  Human  HIV Infections/*DRUG
       THERAPY  *HIV Protease Inhibitors/ADMINISTRATION &
       DOSAGE/PHARMACOKINETICS  In Vitro  Macaca mulatta  Metabolic Clearance
       Rate  Pyridines/*PHARMACOKINETICS  Rats  Virion/METABOLISM  JOURNAL
       ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).