Derivatives of 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine for treating infections with human immunodeficiency virus (HIV) exhibiting multidrug resistance, process for the preparation thereof and pharmaceutically acceptable drug forms

摘要

4'-Ethynylostavudine derivatives according to the invention substituted at 4'-ethynylostavudine 5'-O-position with 12-tetradodecanoyl, 12-bromododecanoyl, 12-methoxydodecanoyl, 12-ethylothiododecanoyl, or 12-azidododecanoyl group (represented by the symbols WA37, WA38, WA40, WA42, WA39 ) in deClPhR„¢ cells exert very high antiviral activity against the wild type HIV-1 strain, as well as against its drug and multidrug resistant strains, without any citotoxicty at the therapeutic concentrations (CC 50 200 µM). These compounds, because of their very low toxicity may be applied at all phases of AIDS, even at the final phase when the T4 lymphocytes level in patients drops down below 200/µL of peripheral blood. The 2',3'- didehydro-3'-deoxy-4'-ethynylothymidine derivatives, according to the invention, are synthesized by the transformation of the known compound 4'-ethynylostavudine ( WA32, wherein R represents hydrogen).