Synthesis and anti-human immunodeficiency virus type 1 activity of novel 3'-spiro nucleoside analogues of TSAO-T

Abstract

Novel 3'-spiro nucleoside analogues of the potent human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitor TSAO-T have been designed, synthesized and tested for their in vitro anti-retroviral activity against HIV-1. In these TSAO analogues the spiro amino-oxathioledioxide moiety was replaced by other spiro moieties that maintained an NH group at the same position as the 4'-NH2 group in the prototype compound TSAO-T. Anti-HIV-1 activity, although around 100-fold less pronounced than that of the parent TSAO-m3T derivative, was observed for the spiro oxazolone derivative. The spiro oxathiazoledioxide compound also showed antiviral activity The corresponding β-D-xylofuranosyl analogues were devoid of antiviral activity; this is in accordance with the behaviour of TSAO-m3T. None of the test compounds were inhibitory to HIV-2 replication. The markedly decreased potency of the spiro oxathiazoledioxide and oxazolone compounds against HIV-1 replication is in agreement with their decreased anti-HIV-1 RT activity.