SYNTHESIS AND ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ACTIVITY OF NOVEL 3'-SPIRO NUCLEOSIDE ANALOGS OF TSAO-T

Novel 3'-spiro nucleoside analogues of the potent human immunodeficien cy virus type 1 (HIV-1) reverse transcriptase (RT) inhibitor TSAO-T ha ve been designed, synthesized and tested for their in vitro antiretrov iral activity against HIV-1. In these TSAO analogues the spiro amino-o xathioledioxide moiety was replaced by other spiro moieties that maint ained an NH group at the same position as the 4 ''-NH2 group in the pr ototype compound TSAO-T. Anti-HIV-l activity, although around 100-fold less pronounced than that of the parent TSAO-m(3)T derivative, was ob served for the spiro oxazolone derivative. The spiro oxathiazoledioxid e compound also showed antiviral activity. The corresponding beta-D-xy lofuranosyl analogues were devoid of antiviral activity; this is in ac cordance with the behaviour of TSAO-m(3)T. None of the test compounds were inhibitory to HIV-2 replication. The markedly decreased potency o f the spiro oxathiazoledioxide and oxazolone compounds against HIV-1 r eplication is in agreement with their decreased anti-HIV-l RT activity .