Document 0577
 DOCN  M9460577
 TI    Novel series of TSAO-T derivatives. Synthesis and anti-HIV-1 activity of
       4-, 5-, and 6-substituted pyrimidine analogues.
 DT    9404
 AU    San-Felix A; Velazquez S; Perez-Perez MJ; Balzarini J; De Clercq E;
       Camarasa MJ; Instituto de Quimica Medica (CSIC), Madrid, Spain.
 SO    J Med Chem. 1994 Feb 18;37(4):453-60. Unique Identifier : AIDSLINE
       MED/94166046
 AB    Several 4-, 5-, and 6-substituted pyrimidine analogues of the new
       anti-HIV-1 lead compound
       [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-beta-D-ribofuranosyl]th-
       ymine] -3'-spiro-5''-(4''-amino-1'',2''-oxathiole 2'',2''-dioxide)
       (TSAO-T) have been prepared and evaluated as inhibitors of HIV-1 and
       HIV-2 replication in cell cultures. Reaction of
       1,2-di-O-acetyl-5-O-benzoyl-3-C-cyano-3-O-mesyl-D-ribofuranose with
       5-substituted pyrimidine bases, followed by treatment with Cs2CO3,
       afforded, stereoselectively, beta-D-ribofuranosyl-3'-spironucleosides.
       2',5'-O-Deacylation and subsequent treatment with
       tert-butyldimethylsilyl chloride gave the TSAO-5-substituted pyrimidine
       derivatives. Reaction of 5-halogen-TSAO derivatives with nucleophiles
       gave 6-substituted-TSAO analogues. Treatment of TSAO-pyrimidine
       analogues with POCl3/1,2,4-triazole and methylamine or di-methylamine
       afforded the 4-substituted pyrimidine compounds. Several substituted
       TSAO-thymine, TSAO-uracil, and TSAO-cytosine derivatives were found to
       be superior to their unsubstituted TSAO congeners with regard to their
       antiviral and/or cytotoxic properties.
 DE    Antiviral Agents/*CHEMICAL SYNTHESIS/*PHARMACOLOGY  Cells, Cultured
       HIV-1/*DRUG EFFECTS  HIV-2/*DRUG EFFECTS  Pyrimidines/*CHEMICAL
       SYNTHESIS/*PHARMACOLOGY  Reverse Transcriptase/*ANTAGONISTS & INHIB
       Structure-Activity Relationship  Support, Non-U.S. Gov't
       Thymidine/*ANALOGS & DERIVATIVES/PHARMACOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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