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 formulations thereof, methods for its preparation and its use as an antiviral agent are described.

1 - 18 . (canceled)  
   
   
       19 . A composition for use in treating an HIV infection in a patient, said composition comprising an amount of a 2′,3′-dideoxy nucleoside compound effective to inhibit the growth or replication of HIV in combination with a toxicity reducing effective amount of the compound (−)-(2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one or a pharmaceutically acceptable salt thereof.  
   
   
       20 . A composition for use in treating an HIV infection in a patient, said composition comprising an amount of an anti-HIV D-nucleoside compound effective to inhibit the growth or replication of HIV in combination with a toxicity reducing effective amount of the L-nucleoside compound (−)-(2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one or pharmaceutically acceptable salt thereof.  
   
   
       21 . A method for reducing the toxicity associated with the administration of a D-nucleoside compound in a patient, comprising co-administering with said D-nucleoside compound a toxicity reducing effective amount of (−)-(2R, cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-one or a pharmaceutically acceptable salt thereof.  
   
   
       22 . A method for reducing the toxicity associated with administration of a 2′,3′-dideoxy nucleoside in a patient comprising co-administering with said 2′,3′-dideoxy nucleoside a toxicity reducing effective amount of (−)-(2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one or a pharmaceutically acceptable salt thereof.  
   
   
       23 . A composition for use in treating an HIV infection in a patient, said composition comprising an amount of an anti-HIV D-nucleoside compound effective to inhibit the growth or replication of HIV in combination with a toxicity reducing effective amount of the L-nucleoside compound β-L-2′-deoxy-3′-thiacytidine or a pharmaceutically acceptable salt thereof.  
   
   
       24 . A method for reducing toxicity associated with the administration of a D-nucleoside compound in a patient, comprising co-administering with said D-nucleoside compound a toxicity reducing effective amount of, β-L-2′-deoxy-3′-thiacytidine or a pharmaceutically acceptable salt thereof.  
   
   
       25 . A composition for use in treating an HIV infection in a patient, said composition comprising an effective amount of a 2′,3′-dideoxy nucleoside compound in combination with an effective amount of the compound (−)-(2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one or a pharmaceutically acceptable salt thereof.  
   
   
       26 . A composition for use in treating an HIV infection in a patient, said composition comprising an amount of an anti-HIV D-nucleoside compound and an amount of the L-nucleoside compound (−)-(2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one or a pharmaceutically acceptable salt thereof.  
   
   
       27 . A composition for use in treating an HIV infection in a patient, said composition comprising an amount of an anti-HIV D-nucleoside compound in combination with an amount of the L-nucleoside compound β-L-2′-deoxy-3′-thiacytidine or a pharmaceutically acceptable salt thereof.