Document 0389
 DOCN  M9590389
 TI    Potent inhibitors of the HIV-1 protease with good oral
       bioavailabilities.
 DT    9509
 AU    Sham HL; Zhao C; Marsh KC; Betebenner DA; Lin S; McDonald E; Vasavanonda
       S; Wideburg N; Saldivar A; Robins T; et al; Abbott Laboratories, Abbott
       Park, Illinois 60064-3500, USA.
 SO    Biochem Biophys Res Commun. 1995 Jun 6;211(1):159-65. Unique Identifier
       : AIDSLINE MED/95298017
 AB    A series of novel pseudo-symmetrical and unsymmetrical inhibitors based
       on the backbone modification of a peptidomimetic were synthesized and
       found to be highly potent inhibitors of the HIV-1 protease (IC50 = 2.9
       to < 0.5 nM). These compounds also possess good antiviral activity in
       vitro as measured by inhibition of the cytopathic effect of HIV-1(3B) in
       MT-4 lymphocytes. Importantly, some of these compounds also have good
       oral bioavailabilities in rats (F = 30.6% to 100%). One of these
       compounds 4C, also has good oral bioavailability in beagle dogs and
       cynomolgus monkeys.
 DE    Animal  Biological Availability  Comparative Study  Dogs  Drug Design
       Female  HIV Protease/METABOLISM  HIV Protease Inhibitors/CHEMICAL
       SYNTHESIS/*PHARMACOLOGY/  *PHARMACOKINETICS  Indicators and Reagents
       Macaca fascicularis  Male  Metabolic Clearance Rate  Molecular Structure
       Rats  Rats, Sprague-Dawley  Structure-Activity Relationship  JOURNAL
       ARTICLE

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