1',2',6'-Thiadiazine 1',1'-Dioxide and Imidazo [4',5'-c][1',2',6']thiadiazine 2',2'-Dioxode 1,3-Oxathiolane Nucleoside Analogues: Synthesis and Anti-HIV-1 Activity

Abstract

A series of IS-oxathiolanes containing the I,2,6-thiadiazine dioxide moieties were synthesized by various coupling conditions of the oxathiolane sugar (3) and silylated 1,2,6thiadiazine dioxides (4-7) as bases.The compounds were evaluated for their potential anti-HIV activities in MT-4 cells and were found to lack activity at 100 pglml.The hetero-substituted 2',3'-dideoxynucleoside analogues have emerged as an important class of antiviral agents,' particularly against the inhibition of the replication of the human immunodetieiency virus (HIV), the causative agent of AIDS, and hepatitis B virus (HBV). (-)-2'-~eox~-3'-thiacytidine~ (1, Lamivudine, ~T C ~~) and its 5-fluoro congener3 have high therapeutic indices for HIV and H B V ~ relative to that of 2',3 '-dideoxycytidine5 (ddC).As part of our research program aimed at modifications in the nucleobase ring, we undertook the synthesis of 1,3-oxathiolanyl nucleosides containing the 1,2,6-thiadiazine 1,l-dioxides as pyrimidine and purine mimetics.Approaches involving base modifications have become useful in identifying novel therapeutic agents, particularly oligonucleotides.We report herein the synthesis and anti-HIV activity6 of a series of racemic 1',Z3,e-thiadiazine dioxide-1,3oxathiolane nucleoside analogues of the general formula (2).