Use of 1,3-oxathiolane nucleoside analogues in the treatment of hepatitis B

Abstract

Use of a compound of formula (I) or a pharmaceutically acceptable derivative thereof in the manufacture of a medicament for the treatment of hepatitis B is disclosed.

1. A method for the treatment of hepatitis B infection, in a mammal, including a human, suffering from hepatitis B infection, comprising administration of an effective amount of a compound of formula (I) 
                 
 
       or a pharmaceutically acceptable salt, ester, or salt of an ester thereof to said mammal. 
     
     
       2. The method according to  claim 1  wherein the hepatitis B infection is human hepatitis B. 
     
     
       3. The method according to  claim 1  wherein the compound of formula (I) comprises (±)-cis-4-amino-1-( 2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one or a pharmaceutically acceptable salt, ester, or salt of an ester thereof. 
     
     
       4. The method according to  claim 1  wherein the compound of formula (I) comprises (−)-cis-4-amino-1-( 2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one or a pharmaceutically acceptable salt, ester, or salt of an ester thereof. 
     
     
       5. The method according to  claim 4  wherein the compound of formula (I) is substantially free of the corresponding (+)-enantiomer. 
     
     
       6. The method according to any one of  claims 1  to  5  wherein the compound of formula (I) is adapted for oral administration. 
     
     
       7. The method according to any one of  claims 1  to  5  wherein the compound of formula (I) is adapted for parenteral administration. 
     
     
       8. The method according to any one of  claims 1  to  5  wherein the compound of formula (I) is in unit dosage form. 
     
     
       9. The method according to  claim 8  wherein the compound is present in an amount of from 10 to 1500 mg. 
     
     
       10. A method for the treatment of hepatitis B infection, in a human, suffering from hepatitis B infection, comprising administering to said human an effective amount of a compound of formula ( I ) 
                   
       
         or a pharmaceutically acceptable salt, ester, or salt of an ester thereof.  
       
     
     
       11. The method according to  claim 10 , wherein the compound of formula ( I )  is  (−)- cis -   4   - amino -   1   -(   2   - hydroxymethyl -   1 , 3   - oxathiolan -   5   - yl )-(   1 H )- pyrimidin -   2   - one or a pharmaceutically acceptable salt, ester or salt of an ester thereof.    
     
     
       12. A method for the treatment of hepatitis B infection, in a human, suffering from hepatitis B infection, comprising administering to said human an effective amount of a compound of formula ( I ) 
                   
       
         or a pharmaceutically acceptable salt thereof.  
       
     
     
       13. The method according to  claim 12 , wherein the compound of formula ( I )  is  (−)- cis -   4   - amino -   1   -(   2   - hydroxymethyl -   1 , 3   - oxathiolan -   5   - yl )-(   1 H )- pyrimidin -   2   - one or a pharmaceutically acceptable salt thereof.    
     
     
       14. The method according to  claim 10 , comprising administering a compound of formula ( I ) .    
     
     
       15. The method according to  claim 13 , comprising administering (−)- cis -   4   - amino -   1   -(   2   - hydroxymethyl -   1 , 3   - oxathiolan -   5   - yl )-(   1 H )- pyrimidin-     2   - one.    
     
     
       16. The method according to  claim 11 , wherein the (−)- cis -   4   - amino -   1   -(   2   - hydroxymethyl -   1 , 3   - oxathiolan -   5   - yl )-(   1 H )- pyrimidin-     2   - one or pharmaceutically acceptable salt thereof is substantially free of the corresponding  (+)- enantiomer.    
     
     
       17. The method according to  claim 13 , wherein the (−)- cis -   4   - amino -   1   -(   2   - hydroxymethyl -   1 , 3   - oxathiolan -   5   - yl )-(   1 H )- pyrimidin-     2   - one or pharmaceutically acceptable salt thereof is substantially free of the corresponding  (+)- enantiomer.    
     
     
       18. The method according to  claim 15 , wherein the (−)- cis -   4   - amino -   1   -(   2   - hydroxymethyl -   1 , 3   - oxathiolan -   5   - yl )-(   1 H )- pyrimidin-     2   - one is substantially free of the corresponding  (+)- enantiomer.