2',5'-BIS-O-(TERT-BUTYLDIMETHYLSILYL)-3'-SPIRO-5''-(4''-AMINO-1',2''-OXATHIOLE-2'',2''-DIOXIDE)PYRIMIDINE (TSAO) NUCLEOSIDE ANALOGS - HIGHLY SELECTIVE INHIBITORS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 THAT ARE TARGETED AT THE VIRAL REVERSE-TRANSCRIPTASE

A series of pyrimidine nucleoside analogues containing [2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1", 2"-oxathiole-2",2"-dioxide)]-beta-D-ribofuranose as the pentose were found to inhibit human immunodeficiency virus type 1 [HIV-1(III(B))] replication at a concentration of 0.06-0.8-mu-M but were not cytotoxic at a 1000- to 10,000-fold higher concentration. These nucleoside derivatives were also effective against various other HIV-1 strains, including those resistant to 3'-azido-3'-deoxythymidine, but not against HIV-2, simian immunodeficiency virus, Moloney murine sarcoma virus, or other RNA or DNA viruses. They proved to be highly specific inhibitors of the RNA-dependent DNA polymerase function of the HIV-1 reverse transcriptase, showing no marked inhibition of the HIV-1 reverse transcriptase-associated DNA-dependent DNA polymerase activity, HIV-2 reverse transcriptase, DNA polymerase-alpha, herpes simplex virus 1 DNA polymerase, or Thermus aquaticus DNA polymerase.