Document 0431
 DOCN  M9490431
 TI    Synthesis and biological properties of
       5-o-carboranyl-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil- .
 DT    9411
 AU    Fulcrand-el Kattan G; Goudgaon NM; Ilksoy N; Huang JT; Watanabe KA;
       Sommadossi JP; Schinazi RF; Veterans Affairs Medical Center (Atlanta),
       Decatur, Georgia; 30033.
 SO    J Med Chem. 1994 Aug 5;37(16):2583-8. Unique Identifier : AIDSLINE
       MED/94334915
 AB    A novel 5-o-carboranyl-containing nucleoside,
       5-o-carboranyl-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil (6,
       CFAU), was synthesized as a potential intracellular neutron capture
       agent. This compound was prepared in five steps starting from
       5-iodo-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)uracil (1). The
       desired carboranyl derivative was obtained by addition of decaborane [as
       the bis(propionitrile) adduct] to the protected acetylenic nucleoside
       precursor followed by debenzoylation. The synthesis of CFAU was also
       performed by glycosylation of the suitably protected
       5-o-carboranyluracil with the appropriate 2-fluoroarabinosyl derivative.
       This compound was evaluated for its cytotoxicity in human lymphocytes,
       monkey cells, and rat and human gliomas cells, as well as for antiviral
       activity against human immunodeficiency virus and herpes simplex virus
       type 1. Its biological activity was compared to
       5-o-carboranyl-1-(2-deoxyribofuranosyl)uracil in these cell culture
       systems, human bone marrow cells, and mice. The results obtained to date
       suggest that CFAU has suitable characteristics as a sensitizer for boron
       neutron capture therapy.
 DE    Animal  Antiviral Agents/*CHEMICAL SYNTHESIS/PHARMACOLOGY
       Arabinofuranosyluracil/*ANALOGS & DERIVATIVES/CHEMICAL SYNTHESIS/
       PHARMACOLOGY/TOXICITY  Bone Marrow/DRUG EFFECTS  Boron
       Compounds/*CHEMICAL SYNTHESIS/PHARMACOLOGY/TOXICITY  *Boron Neutron
       Capture Therapy  Cell Survival/DRUG EFFECTS  Female  Glioma/PATHOLOGY
       Glycosylation  Herpesvirus 1, Human/DRUG EFFECTS  Human  HIV-1/DRUG
       EFFECTS  Lymphocytes/DRUG EFFECTS  Mice  Radiation-Sensitizing
       Agents/*CHEMICAL SYNTHESIS  Rats  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, Non-P.H.S.  Support, U.S. Gov't, P.H.S.  Tumor Cells, Cultured
       JOURNAL ARTICLE

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