Nucleosides with anti-hepatitis B Virus activity

Abstract

A method for the treatment of a host, and in particular, a human, infected with hepatitis B virus (HBV) is provided that includes administering an effective amount of a β-L-nucleotide, optionally in combination therapy with other drugs for the treatment of HBV or human immuno-deficiency virus (HIV).

1 . A method for the treatment of HBV infection of 
     
       
         
         
             
             
         
       
     
     wherein B is a purine or pyrimidine base;
 Y 1 , Y 2 , Y 3 , and Y 4  are independently H, OH, N 3 , NR 1 R 2 , NO 2 , NOR 3 , —O-alkyl, —O-aryl, halo (including F, Cl, Br, or I), —CN, —C(O)NH 2 , SH, —S-alkyl, or —S-aryl, and wherein typically three of Y 1 , Y 2 , Y 3 , and Y 4  are either H or OH. The —OH substituent, when present, is typically a Y 1  or Y 3  group. As illustrated in the structure, Y 2  and Y 4  are in the arabino (erythro) configuration, and Y 1  and Y 3  are in the threo (ribose) configuration. R is H, monophosphate, diphosphate, triphosphate, alkyl, acyl or a phosphate derivative, as described in more detail below. R 1 , R 2 , and R 3  are independently alkyl (and in particular lower alkyl), aryl, aralkyl, alkaryl, acyl, or hydrogen.