Document 0843
 DOCN  M9550843
 TI    Characterization of the anti-HIV-1 activity of
       3,4-dihydro-2-alkoxy-6-benzyl-4-oxopyrimidines (DABOs), new
       non-nucleoside reverse transcriptase inhibitors.
 DT    9505
 AU    Tramontano E; Marongiu ME; de Montis A; Loi AG; Artico M; Massa S; Mai
       A; la Colla P; Dipartimento di Biologia Sperimentale, Universita di
       Cagliari,; Italy.
 SO    Microbiologica. 1994 Oct;17(4):269-79. Unique Identifier : AIDSLINE
       MED/95166036
 AB    Novel 3,4-dihydro-6-benzyl-4-oxopyrimidines (DABOs), variously
       substituted at both the C-2 and C-5 positions of the pyrimidine ring,
       proved to be specific inhibitors of the human immunodeficiency virus
       type 1 (HIV-1) in vitro. Some compounds showed potency at micromolar
       doses, no cytotoxicity at the maximum testable doses and selectivity
       indexes comparable to that of 2'-3'-dideoxyinosine (ddI). Mode of action
       studies suggested that DABOs interfered with a step of the virus
       multiplication cycle following adsorption and preceding integration.
       Enzyme assays indicated that DABOs targeted HIV-1 reverse transcriptase:
       they inhibited the RNA-dependent DNA polymerase activity in a
       template-dependent manner and, to a lesser extent, the DNA-dependent DNA
       polymerase activity. No inhibition of the RNase-H associated activity
       was observed. When DABOs were assayed in combination with
       3'-azido-3'-dideoxythymidine (AZT) or ddI against HIV-1 in cell
       cultures, a slightly synergistic inhibitory effect was observed. The
       combination of DABO 546 and AZTTP in enzyme assays showed that the two
       compounds were kinetically mutually exclusive.
 DE    Antiviral Agents/CHEMISTRY/*PHARMACOLOGY/TOXICITY  Cells, Cultured
       Comparative Study  Drug Interactions  HIV-1/*DRUG
       EFFECTS/ENZYMOLOGY/GROWTH & DEVELOPMENT
       Pyrimidines/*PHARMACOLOGY/TOXICITY  Pyrimidinones/PHARMACOLOGY  Reverse
       Transcriptase/*ANTAGONISTS & INHIB  Support, Non-U.S. Gov't  Thymine
       Nucleotides/PHARMACOLOGY  Virus Replication/DRUG EFFECTS
       Zidovudine/ANALOGS & DERIVATIVES/PHARMACOLOGY  JOURNAL ARTICLE

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