beta-L-2'-Deoxy-Nucleosides for the Treatment of Hepatitis B

Abstract

This invention is directed to a method for treating a host infected with hepatitis B comprising administering an effective amount of an anti-HBV biologically active 2′-deoxy-β-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof, wherein the 2′-deoxy-β-L-erythro-pentofuranonucleoside has the formula: wherein R is selected from the group consisting of H, straight chained, branched or cyclic alkyl, CO-alkyl, CO-aryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate, or a phosphate derivative; and BASE is a purine or pyrimidine base which may be optionally substituted. The 2′-deoxy-β-L-erythro-pentofuranonucleoside or a pharmaceutically acceptable salt or prodrug thereof may be administered either alone or in combination with another 2′-deoxy-β-L-erythro-pentofuranonucleoside or in combination with another anti-hepatitis B agent.

1 - 12 . (canceled)  
     
     
         13 . A pharmaceutical composition to treat a patient with a hepatitis B virus infection, which comprises an effective amount of β-L-2′-deoxvthvmidine or its pharmaceutically acceptable salt in combination with a pharmaceutically acceptable carrier, wherein: (i) the β-L-2′-deoxythymidine is present in the pharmaceutical composition in an amount from 50-1000 mg; and (ii) the pharmaceutical composition is suitable for oral delivery.  
     
     
         14 - 21 . (canceled)  
     
     
         22 . The pharmaceutical composition of  claim 13 , wherein the composition is in the form of a tablet, pill or capsule.  
     
     
         23 . The pharmaceutical composition of  claim 22 , wherein the composition is in the form of a tablet.  
     
     
         24 . The pharmaceutical composition of  claim 22 , wherein the composition is in the form of a pill.  
     
     
         25 . The pharmaceutical composition of  claim 22 , wherein the composition is in the form of a capsule.  
     
     
         26 . The pharmaceutical composition of  claim 13 , wherein β-L-2′-deoxythymidine is present in the pharmaceutical composition in an amount of at least 600 mg.  
     
     
         27 . The pharmaceutical composition of  claim 13 , wherein the β-L-2′-deoxythymidine is present in the pharmaceutical composition in an amount of at least 400 mg.  
     
     
         28 . The pharmaceutical composition of  claim 13 , wherein the β-L-2′-deoxythymidine is present in the pharmaceutical composition in an amount of at least 200 mg.  
     
     
         29 . The pharmaceutical composition of  claim 13 , wherein the β-L-2′-deoxythymidine is at least 95% in its designated enantiomeric form.  
     
     
         30 . The pharmaceutical composition of  claim 13 , wherein the β-L-2′-deoxythymidine is at least 98% in its designated enantiomeric form.  
     
     
         31 . The pharmaceutical composition of  claim 13 , wherein the β-L-2′-deoxythymidine is at least 99% in its designated enantiomeric form.  
     
     
         32 . The pharmaceutical composition of  claim 13  wherein the β-L-2′-deoxythymidine is in combination with an effective amount of a compound selected from the group consisting of β-L-2-hydroxymethyl-5-(cytosin-1-yl)-1,3-oxathiolane (3TC), cis-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane (FTC), β-L-2′-fluoro-5-methyl-arabinofuranolyl-uridine (L-FMAU), β-D-2,6-diaminopurine dioxolane (DAPD), famciclovir, penciclovir, 2-amino-1,9-dihydro-9-[4-hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl]-6H-purin-6-one (entecavir, BMS-200475), 9-[2-(phosphono-methoxy)ethyl]adenine (PMEA, adefovir, dipivoxil); lobucavir, ganciclovir and ribavirin.