Analogs of 2',3'-dideoxy-3'-fluorothymidine 5'-monophosphate (FLTMP) for treatment human immunodeficiency virus (HIV), their application and pharmaceutically acceptable form of drug

摘要

Analogs of 3'-fluorothymidine 5'-monophosphate (FLTMP), preferably intended 2',3'-dideoxy-3'-fluoro-β-D-erythro-pentofuranoside of thymine 5'-monophosphate (FLTMP): 3'-fluoro-2-thiothymidine 5'-monophosphate intended 2',3'-dideoxy-3'-fluoro-β-D-erythro-pentofuranoside of 2-thiothymine 5'-monophosphate; 3'-fluoro-4-thiothymidine 5'-monophosphate is intended 2',3'-dideoxy-3'-fluoro-β-D-erythro-pentofuranoside of 4-thiothymine 5'-monophosphate (4-SFLTMP).;This invention includes also medical use of analogues of 3'-fluorothymidine 5'-monophosphate (FLTMP), according to the invention, Formula 1, for therapy of infections caused by the human immunodeficiency virus (HIV-1) wild type strain and strains showing resistance and multidrug resistance.;The inventors unexpectedly discovered that proposed new FLTMP analogs with thiosubstituent at 2 or 4 position of FLT pyrimidine ring and monophosphate group at 5'-0-of 2,3-dideoxyribose exert very potent inhibitory activity against drug and multidrug resistant HIV-1 strains, as well as show high selectivity and good solubility in water.;This invention also includes pharmaceutical acceptable form of drug, which according to the invention, contain known acceptable media and auxiliary substances, containing, as an active compounds analogues of general Formula 1, in which X, Y and R have the above-mentioned importance, especially the relationship being dilithium salt of 2-SFLTMP and 4-SFLTMP.