Modified 2',3'-dideoxynucleosides for treatment infections caused by human immunodeficiency virus (HIV) multidrug resistant strains, method of their synthesis and the pharmaceutical agent containing these nucleosides

摘要

2',3'-Dideoxy-3'-fluoro-4-thiothymidine (4-SFLT) derivatives according to the invention substituted at 5'-O position of 4-SFLT with 12-tetradodecanoyl, 12-bromododecanoyl, 12-metoxydodecanoyl, 12-ethylothiododecanoyl, 11-ethylothioundecanoyl or 12-azidodocanoyl group (represented by the symbols WA18, WA19, WA21,WA22,WA23 and WA20 in the deCIPhR™ cell system exert high antiviral activity against wild type HIV-1 strain, as well as against its drug and multidrug resistant strains, and moreover very low citotoxicity (CC₅₀ 200 µM) and very high selectivity.;The compounds, because of lack of toxicity may be applied at all AIDS phases i.e. also them the T4 lymphocytes level in patients drops down below 200/ µL of peripheral blood.;2',3'-Dideoxy-3'-fluoro-4-thiothymidine derivatives according to the invention are synthesized by the transformation of the known compound 2',3'-dideoxy-3'-fluoro-4-thiothymidine (4-SFLT).