β-L-2'-deoxy-nucleosides for the treatment of hepatitis B

A method for the treatment or prophylaxis of a hepatitis B virus infection in a host comprising administering an effective amount of β-L-thymidine of the formula:

• or a pharmaceutically acceptable salt or prodrug thereof, wherein R is selected from the group consisting of H, —CO-alkyl, —CO-aryl, —CO-alkoxyalkyl, —CO-aryloxyalkyl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate or a stabilized nucleotide.

A method for the treatment or prophylaxis of a hepatitis B virus in a host comprising administering a effective combination of the compounds

• or a pharmaceutically acceptable salt or prodrug thereof, wherein R is hydrogen or acyl.

A method for the treatment or prophylaxis of a hepatitis B virus infection in a host comprising administering an effective amount of a compound of the formula:

• or a pharmaceutically acceptable salt or prodrug thereof, wherein R is selected from the group consisting of H, —CO-alkyl, —CO-aryl, —CO-alkoxyalkyl, —CO-aryloxyalkyl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate or a stabilized nucleotide;
• in combination or alternation 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-arabinouridine (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.

A method for the treatment or prophylaxis of a hepatitis B virus infection in a host comprising administering an effective amount of a compound of the formula:

• or a pharmaceutically acceptable salt or prodrug thereof, wherein R is selected from the group consisting of H, —CO-alkyl, —CO-aryl, —CO-alkoxyalkyl, —CO-aryloxyalkyl, alkylsulfonyl, arylsulfonyl, aralkylsulfonyl, amino acid residue, mono, di, or triphosphate or a stabilized nucleotide;
• in combination or alternation 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-arabinouridine (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.

A compound or pharmaceutically acceptable salt or prodrug thereof of the formula:

• wherein R is H, mono, di or tri phosphate, amino acid residue, acyl, or alkyl, or a stabilized phosphate derivative (to form a stabilized nucleotide prodrug).

A method for the treatment or prophylaxis of a hepatitis B virus infection in a host comprising administering an effective amount of compound of the formula:

• or a pharmaceutically acceptable salt thereof, wherein R is an amino acid residue.

A method for the treatment or prophylaxis of a hepatitis B virus infection in a host comprising administering an effective amount of compound of the formula:

• or a pharmaceutically acceptable salt thereof, wherein R is an amino acid residue.

A method for the treatment or prophylaxis of a hepatitis B virus in a host comprising administering a effective combination of the compounds

• or a pharmaceutically acceptable salt or prodrug thereof, wherein R is hydrogen or an amino acid residue.

A method for the treatment or prophylaxis of a hepatitis B virus infection in a host comprising administering an effective amount of a compound of the formula:

• or a pharmaceutically acceptable salt or prodrug thereof, wherein R is an amino acid residue;
• in combination or alternation 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-arabinouridine (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.

A method for the treatment or prophylaxis of a hepatitis B virus infection in a host comprising administering an effective amount of a compound of the formula:

• or a pharmaceutically acceptable salt or prodrug thereof, wherein R is an amino acid residue;
• in combination or alternation 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-arabinouridine (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.

A compound of the formula:

• or pharmaceutically acceptable salt thereof.

A compound of the formula:

• or pharmaceutically acceptable salt thereof.

A method for treating a host infected with hepatitis B comprising administering an effective amount of β-L-2′-deoxycytidine of the formula:

• or its pharmaceutically acceptable salt, optionally in a pharmaceutically acceptable carrier.

A method for treating a host infected with hepatitis B comprising administering an effective amount of β-L-2′-deoxythymidine of the formula:

• or its pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.