1,3-oxathiolane nucleoside analogues

Abstract

(−)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one, its pharmaceutically acceptable derivatives, pharmaceutical formulation thereof, methods for its preparation and its uses as an antiviral agent are described

1 . (−)-cis-4-amino-1-(2-hydroxymethy-1,3-oxathiolane-5-yl)-(1H)-pyrimidin-2-one or a pharmaceutically acceptable derivative thereof.  
     
     
         2 . A compound as claimed in  claim 1  substantially free of the corresponding (+)-enantiomer.  
     
     
         3 . A compound as claimed in  claim 1  or  claim 2  wherein the (+)-enantiomer is present in an amount of no more than about 5% w/w.  
     
     
         4 . A compound as claimed in any one of  claims 1  to  3  wherein the (+)-enantiomer is present in an amount of no more than about 2% w/w.  
     
     
         5 . A compound as claimed in any one of  claims 1  to  4  wherein the (+)-enantiomer is present in an amount of less than about 1% w/w.  
     
     
         6 . A compound as claimed in  claim 1  in substantially pure form.  
     
     
         7 . A pharmaceutical composition comprising a compound as claimed in any one of  claims 1  to  6  together with a pharmaceutically acceptable carrier therefor.  
     
     
         8 . A compound as claimed in any one of  claims 1  to  6  for use in therapy.  
     
     
         9 . Use of a compound as claimed in any one of  claims 1  to  6  for the manufacture of a medicament for the treatment of a viral infection.  
     
     
         10 . A method for the treatment of a mammal, including man, suffering from or susceptible to viral infection comprising administration of an effective amount of a compound as claimed in any one of  claims 1  to  6 .  
     
     
         11 . A method for the preparation of a compound as claimed in any one of  claims 1  to  6  which comprises separation of the (−)-enantiomer from a mixture also containing the (+)-enantiomer.  
     
     
         12 . A method as claimed in  claim 11  wherein the mixture of compounds is a racemic mixture.  
     
     
         13 . A method as claimed in  claim 11  or  claim 12  the separation is effected by chiral HPLC.  
     
     
         14 . A method as claimed in  claim 13  wherein the HPLC employs as a stationary phase acetylated β-cyclodextrin or cellulose triacetate.  
     
     
         15 . A method as claimed in  claim 11  or  claim 12  wherein the separation is effected by enzyme-mediated enantioselective catabolism.  
     
     
         16 . A method is claimed in  claim 15  wherein the enzyme is employed in immobilised form.  
     
     
         17 . A method as claimed in  claim 15  or  claim 16  wherein the enzyme is cytidine deaminase.  
     
     
         18 . A method as claimed in  claim 15  or  claim 16  wherein the enzyme is a 5′-nucleotidase.