Document 0343
 DOCN  M9440343
 TI    Differential antiviral activity of two TIBO derivatives against the
       human immunodeficiency and murine leukemia viruses alone and in
       combination with other anti-HIV agents.
 DT    9404
 AU    Buckheit RW Jr; Germany-Decker J; Hollingshead MG; Allen LB; Shannon WM;
       Janssen PA; Chirigos MA; Virology Research Division, Southern Research
       Institute-Frederick; Research Center, Maryland 21701.
 SO    AIDS Res Hum Retroviruses. 1993 Nov;9(11):1097-106. Unique Identifier :
       AIDSLINE MED/94145744
 AB    R82913 and R86183, two derivatives of
       tetrahydroimidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-thione (TIBO), were
       found to potently and selectively inhibit the replication and cell
       killing effects of a panel of biologically diverse laboratory and
       clinical strains of HIV-1. The two compounds exhibited significant
       activity in all human cell lines tested, as well as in fresh human
       peripheral blood lymphocytes and macrophages. One of these two compounds
       (R82913) was found to significantly inhibit the replication of a murine
       retrovirus (Rauscher murine leukemia virus) in both UV-XC plaque
       formation and virus yield reduction assays. R86183, despite differing
       from R82913 only in the positioning of a single chlorine molecule, was
       not active against the murine retrovirus but was 10-fold more potent in
       inhibiting HIV-1 replication. Combination antiviral assays with other
       reverse transcriptase inhibitors, including AZT, ddC, and carbovir,
       yielded synergistic anti-HIV activity with both TIBO derivatives.
       Additive to slightly synergistic results were obtained in combinations
       with ddI and phosphonoformic acid whereas additive to antagonistic
       activity was detected in combination with dextran sulfate.
 DE    Animal  Antiviral Agents/ADMINISTRATION & DOSAGE/*PHARMACOLOGY
       Benzodiazepines/ADMINISTRATION & DOSAGE/*PHARMACOLOGY  Cell Line
       Comparative Study  Didanosine/ADMINISTRATION & DOSAGE  Drug Synergism
       Human  HIV-1/*DRUG EFFECTS/PHYSIOLOGY  HIV-2/DRUG EFFECTS/PHYSIOLOGY
       Imidazoles/ADMINISTRATION & DOSAGE/*PHARMACOLOGY  Mice  Rauscher
       Virus/*DRUG EFFECTS/PHYSIOLOGY  Reverse Transcriptase/ANTAGONISTS &
       INHIB  Support, U.S. Gov't, P.H.S.  Virus Replication/DRUG EFFECTS
       Zidovudine/ADMINISTRATION & DOSAGE  JOURNAL ARTICLE

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