2'-c-methyl-ribofuranosyl cytidine prodrugs, pharmaceutical compositions, and uses thereof

Abstract

The present disclosure provides 2′-C-methyl-ribofuranosyl cytidine prodrugs, methods of making 2′-C-methyl-ribofuranosyl cytidine prodrugs, pharmaceutical compositions of 2′-C-methyl-ribofuranosyl cytidine prodrugs, and methods of using 2′-C-methyl-ribofuranosyl cytidine prodrugs and pharmaceutical compositions thereof to treat viral diseases such as hepatitis C.

1 - 60 . (canceled) 
     
     
         61 . A method of treating a patient infected with hepatitis C, comprising administering to the patient a therapeutically effective amount of a compound of structural Formula (I): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof and a therapeutically effective amount of a second anti-viral agent or a pharmaceutically acceptable salt thereof;
 wherein: 
 R 1  is selected from hydrogen, acyl, substituted acyl, acyloxyalkylcarbonyl, substituted acyloxyalkylcarbonyl, oxycarbonyl, substituted oxycarbonyl, and 
 
       
         
           
           
               
               
           
         
         R 2  is selected from hydrogen, acyl, substituted acyl, acyloxyalkylcarbonyl, substituted acyloxyalkylcarbonyl, oxycarbonyl, substituted oxycarbonyl, and 
       
       
         
           
           
               
               
           
         
         R 3  is selected from —N═C(R 10 )(R 11 ) and —NHR 12 ; 
         R 4  and R 7  are independently selected from hydrogen, alkyl, substituted alkyl, acyl, substituted acyl, acyloxyalkylcarbonyl, substituted acyloxyalkylcarbonyl, arylalkyl, substituted arylalkyl, oxycarbonyl, and substituted oxycarbonyl; 
         R 5  and R 8  are independently selected from hydrogen, alkyl, substituted alkyl, arylalkyl, substituted arylalkyl, cycloalkyl, and substituted cycloalkyl; 
         R 6  and R 9  are independently selected from hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, substituted acyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbamoyl, substituted carbamoyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl; 
         or R 5  and R 6  together with the nitrogen atom to which they are bonded form a cycloheteroalkyl or substituted cycloheteroalkyl ring; 
         or R 8  and R 9  together with the nitrogen atom to which they are bonded form a cycloheteroalkyl or substituted cycloheteroalkyl ring; 
         R 10  and R 11  are independently selected from hydrogen, acyl, substituted acyl, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkylamino, substituted alkylamino, amido, substituted amido, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, dialkylamino, substituted dialkylamino, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl; 
         R 12  is selected from acyloxyalkylcarbonyl, substituted acyloxyalkylcarbonyl, oxycarbonyl, substituted oxycarbonyl, and a moiety of structural Formula (II): 
       
       
         
           
           
               
               
           
         
       
       wherein:
 X is selected from O and CH 2 ; 
 q is selected from 1 and 2; 
 each R 13  and R 14  are independently selected from hydrogen, C 1-4  alkyl, phenyl, and substituted phenyl; or R 13  and R 14  together with the carbon atom to which they are both bonded form a C 3-7  cycloalkyl ring; 
 R 15  is selected from hydrogen, C 1-4  alkyl, and —CO 2 R 17 ; 
 W is selected from O and NR 18 ; 
 R 17  is selected from hydrogen, C 1-4  alkyl, phenyl, and substituted phenyl; 
 R 18  is selected from hydrogen and C 1-4  alkyl; 
 R 16  is selected from C 1-4  alkyl, —C(O)R 19 , —C(O)OR 20 , 
 
       
         
           
           
               
               
           
         
       
       wherein:
 R 19  is selected from hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl; 
 R 20  is selected from C 1-6  alkyl, C 3-7  cycloalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, and substituted heteroaryl; 
 R 21  and R 22  are independently selected from hydrogen, alkyl, substituted alkyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbamoyl, cycloalkyl, substituted cycloalkyl, cycloalkoxycarbonyl, substituted cycloalkoxycarbonyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl; or R 21  and R 22  together with the carbon atom to which they are bonded form a cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, or substituted cycloheteroalkyl ring; 
 R 23  is selected from acyl, substituted acyl, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl; 
 R 24  is selected from hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, substituted acyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbamoyl, substituted carbamoyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl; and 
 R 25  is selected from hydrogen and C 1-4  alkyl; or R 24  and R 25  together with the carbon to which they are bonded form a cycloalkyl or cycloheteroalkyl ring; 
 wherein “substituted” is a group, wherein one or more hydrogen atoms are independently replaced with halogen, —OH, —CN, —CF 3 , ═O, —NO 2 , C 1-3  alkoxy, C 1-3  alkyl, —COOR 64  wherein R 64  is selected from hydrogen and C 1-3  alkyl, and —NR 65   2  wherein each R 65  is independently selected from hydrogen and C 1-3  alkyl; 
 with the provisos that: 
 R 3  is not phenylcarbonylamino; and 
 when R 3  is —NHR 12  wherein R 12  is a moiety of structural Formula (II), X is CH 2 , and W is O; then R 16  is not C 1-4  alkyl. 
 
     
     
         62 . The method of  claim 61 , wherein the second antiviral agent is selected from an interferon, ribavirin, interleukin, an NS3 protease inhibitor, a cysteine protease inhibitor, a thiazolidine derivative, thiazolidine, benzanilide, phenanthrenequinone, a helicase inhibitor, a polymerase inhibitor, a nucleotide analogue, gliotoxin, cerulenin, antisense phosphorothioate oligodeoxynucleotides, an inhibitor of IRES-dependent translation and a ribozyme. 
     
     
         63 . The method of  claim 62 , wherein the second antiviral agent is selected from interferon-alpha, ribavirin, thiazolidine, benzanilide, phenanthrenequinone, gliotoxin and cerulenin. 
     
     
         64 . The method of  claim 63 , wherein the second antiviral agent is interferon-alpha. 
     
     
         65 . The method of  claim 61 , wherein R 1  is selected from hydrogen, acyl, substituted acyl, acyloxyalkylcarbonyl, substituted acyloxyalkylcarbonyl, oxycarbonyl, and substituted oxycarbonyl. 
     
     
         66 . The method of  claim 61 , wherein R 2  is selected from hydrogen, acyl, substituted acyl, acyloxyalkylcarbonyl, substituted acyloxyalkylcarbonyl, oxycarbonyl, and substituted oxycarbonyl. 
     
     
         67 . The method of  claim 61 , wherein R 3  is)-N═C(R 10 )(R 11 ), wherein R 10  and R 11  are independently selected from hydrogen, alkoxy, substituted alkoxy, alkyl, substituted alkyl, alkylamino, substituted alkylamino, amido, substituted amido, aryl, substituted aryl, arylalkyl, substituted arylalkyl, dialkylamino, substituted dialkylamino, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl. 
     
     
         68 . The method of  claim 61 , wherein R 3  is —NHR 12 , and R 12  is selected from acyloxyalkylcarbonyl, substituted acyloxyalkylcarbonyl, oxycarbonyl, substituted oxycarbonyl, and a moiety of structural Formula (II). 
     
     
         69 . The method of  claim 61 , wherein R 4  and R 7  are independently selected from hydrogen, acyl, substituted acyl, acyloxyalkylcarbonyl, substituted acyloxyalkylcarbonyl, oxycarbonyl, and substituted oxycarbonyl. 
     
     
         70 . The method of  claim 61 , wherein R 5  and R 8  are independently selected from hydrogen, alkyl, substituted alkyl, arylalkyl, substituted arylalkyl, cycloalkyl, and substituted cycloalkyl. 
     
     
         71 . The method of  claim 61 , wherein R 6  and R 9  are independently selected from hydrogen, alkanyl, substituted alkanyl, aryl, substituted aryl, arylalkanyl, substituted arylalkanyl, cycloalkanyl, heteroarylalkyl, and substituted heteroarylalkanyl. 
     
     
         72 . The method of  claim 61 , wherein:
 R 1  is selected from hydrogen, acyl, substituted acyl, acyloxyalkylcarbonyl, substituted acyloxyalkylcarbonyl, oxycarbonyl, substituted oxycarbonyl, and   
       
         
           
           
               
               
           
         
         R 2  is selected from hydrogen, acyl, substituted acyl, acyloxyalkylcarbonyl, substituted acyloxyalkylcarbonyl, oxycarbonyl, substituted oxycarbonyl, and 
       
       
         
           
           
               
               
           
         
         R 3  is —NHR 12 , wherein R 12  is a moiety of structural Formula (II): 
       
       
         
           
           
               
               
           
         
         wherein 
         X is selected from O and CH 2 ; 
         q is selected from 1 and 2; 
         each R 13  and R 14  is independently selected from hydrogen, C 1-4  alkyl, phenyl, and substituted phenyl; or R 13  and R 14  together with the carbon atom to which they are both bonded form a C 3-7  cycloalkyl ring; 
         R 15  is selected from hydrogen, C 1-4  alkyl, and —CO 2 R 17 ; 
         W is selected from O and NR 18 ; 
         R 17  is selected from hydrogen, C 1-4  alkyl, phenyl, and substituted phenyl; 
         R 18  is selected from hydrogen and C 1-4  alkyl; and 
         R 16  is selected from C 1-4  alkyl, —C(O)R 19 , —C(O)OR 20 , 
       
       
         
           
           
               
               
           
         
       
       wherein:
 R 19  is selected from hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl; 
 R 20  is selected from C 1-6  alkyl, C 3-7  cycloalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, and substituted heteroaryl; 
 R 21  and R 22  are independently selected from hydrogen, alkyl, substituted alkyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbamoyl, cycloalkyl, substituted cycloalkyl, cycloalkoxycarbonyl, substituted cycloalkoxycarbonyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl; or R 21  and R 22  together with the carbon atom to which they are bonded form a cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, or substituted cycloheteroalkyl ring; 
 R 23  is selected from acyl, substituted acyl, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl; 
 R 24  is selected from hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, substituted acyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbamoyl, substituted carbamoyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl; and 
 R 25  is selected from hydrogen and C 1-4  alkyl; or R 24  and R 25  together with the carbon to which they are bonded form a cycloalkyl or cycloheteroalkyl ring; 
 with the proviso that: 
 when X is CH 2  and W is O; then R 16  is not C 1-4  alkyl. 
 
     
     
         73 . The method of  claim 72 , wherein R 21  is selected from hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, cyclopentyl, cyclohexyl, phenyl, benzyl, phenethyl, and 3-pyridyl; and R 22  is hydrogen. 
     
     
         74 . The method of  claim 72 , wherein R 23  is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pent-1-yl, pent-2-yl, pent-3-yl, 2-methylbut-1-yl, 3-methylbut-1-yl, 1,1-dimethoxyethyl, 1,1-diethoxyethyl, phenyl, 2-methylphenyl, 2,6-dimethylphenyl, 2-methoxyphenyl, 4-methoxyphenyl, 2,6-dimethoxyphenyl, benzyl, phenethyl, styryl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and 3-pyridyl. 
     
     
         75 . The method of  claim 72 , wherein R 24  is selected from hydrogen, methyl, isopropyl, isobutyl, sec-butyl, tert-butyl, cyclopentyl, cyclohexyl, —CH 2 OH, —CH(OH)CH 3 , —CH 2 CO 2 H, —CH 2 CH 2 CO 2 H, —CH 2 CONH 2 , —CH 2 CH 2 CONH 2 , —CH 2 CH 2 SCH 3 , —CH 2 SH, —CH 2 (CH 2 ) 3 NH 2 , —CH 2 CH 2 CH 2 NHC(NH)NH 2 , phenyl, benzyl, 4-hydroxybenzyl, 4-imidazolylmethyl, and 3-indolylmethyl. 
     
     
         76 . The method of  claim 72 , wherein:
 X is O;   q is 1;   each of R 13  and R 14  is hydrogen;   R 15  is hydrogen;   W is NR 18 , wherein R 18  is hydrogen; and   R 16  is   
       
         
           
           
               
               
           
         
       
     
     
         77 . The method of  claim 72 , wherein:
 X is O;   q is 1;   each of R 13  and R 14  is hydrogen;   R 15  is selected from hydrogen and —CO 2 H;   W is selected from O and NR 18  wherein R 18  is selected from hydrogen and methyl; and   R 16  is selected from   
       
         
           
           
               
               
           
         
       
       methyl, —C(O)R 19 , and —C(O)OR 20 . 
     
     
         78 . The method of  claim 77 , wherein:
 R 1  is hydrogen;   R 2  is hydrogen;   R 24  is selected from hydrogen, methyl, isopropyl, isobutyl, sec-butyl, tert-butyl, cyclopentyl, cyclohexyl, —CH 2 OH, —CH(OH)CH 3 , —CH 2 CO 2 H, —CH 2 CH 2 CO 2 H, —CH 2 CONH 2 , —CH 2 CH 2 CONH 2 , —CH 2 CH 2 SCH 3 , —CH 2 SH, —CH 2 (CH 2 ) 3 NH 2 , —CH 2 CH 2 CH 2 NHC(NH)NH 2 , phenyl, benzyl, 4-hydroxybenzyl, 4-imidazolylmethyl, and 3-indolylmethyl; and   R 25  is hydrogen.   
     
     
         79 . The method of  claim 72 , wherein:
 X is O;   q is 1;   each of R 13  and R 14  is hydrogen;   R 15  is hydrogen;   W is NR 18 , wherein R 18  is selected from hydrogen and methyl; and   R 16  is   
       
         
           
           
               
               
           
         
         wherein R 21  is selected from hydrogen, methyl, ethyl, propyl, isopropyl, tert-butyl, cyclopentyl, cyclohexyl, and phenyl; 
         R 22  is hydrogen; and 
         R 23  is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pent-1-yl, pent-2-yl, pent-3-yl, 2-methylbut-1-yl, 3-methylbut-1-yl, 1,1-dimethoxyethyl, 1,1-diethoxyethyl, phenyl, 2-methylphenyl, 2,6-dimethylphenyl, 2-methoxyphenyl, 4-methoxyphenyl, 2,6-dimethoxyphenyl, benzyl, phenethyl, styryl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and 3-pyridyl. 
       
     
     
         80 . The method of  claim 61 , wherein the compound of structural Formula (I) is selected from:
 β-1-(4-allyloxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-(4-benzyloxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-(4-ethoxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-(4-ethoxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-5-O-(tert-butyldimethylsilyl)-2-C-methyl-ribofuranose;   β-1-(4-ethoxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-3-O—(N-tert-butyloxycarbonyl-L-valinyl)-5-O-(tert-butyldimethylsilyl)-2-C-methyl-ribofuranose;   β-1-(4-ethoxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-3-O-(L-valinyl)-2-C-methyl-ribofuranose;   β-1-(4-ethoxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-3-O-(tetrahydropyranyl)-5-β-(tert-butyldimethylsilyl)-2-C-methyl-ribofuranose;   β-1-(4-ethoxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-3-O-(tetrahydropyranyl)-2-C-methyl-ribofuranose;   β-1-(4-ethoxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-3-O-(tetrahydropyranyl)-5-O—(N-tert-butoxycarbonyl-L-valinyl)-2-C-methyl-ribofuranose;   β-1-(4-ethoxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-5-O-(L-valinyl)-2-C-methyl-ribofuranose;   β-1-(4-allyloxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-5-O-(tert-butyldimethylsilyl)-2-C-methyl-ribofuranose;   β-1-(4-Pentyloxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-(4-Pentyloxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-3-O-(pentyloxycarbonyl)-2-C-methyl-ribofuranose;   β-1-(4-Pentyloxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-5-O-(pentyloxycarbonyl)-2-C-methyl-ribofuranose;   β-1-(4-Pentyloxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-3-O-(pentyloxycarbonyl)-5-O-(pentyloxycarbonyl)-2-C-methyl-ribofuranose;   β-1-(4-Phenyloxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-(4-(4-Methoxyphenyl)oxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-(4-(1,1,1-Trifluoroethyl)oxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-(4-(4-Methoxybenzyl)oxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-(4-(Propen-2-yl)oxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-(4-(2-Carboxy-2-methyl)ethoxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-(4-Pentyloxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-5-O-acetyl-2-C-methyl-ribofuranose;   β-1-(4-Pentyloxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-3-O-acetyl-2-C-methyl-ribofuranose;   β-1-(4-Acetoxymethoxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-(4-(1-Isobutanoyloxyethoxy)carbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-(4-(2,6-Dimethylbenzoyl)oxymethoxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-(4-(2-Methylbenzoyl)oxymethoxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-(4-Acetoxymethoxycarbonylamino-2-oxo-1H-pyrimidin-1-yl)-5-O-(L-valinyl)-2-C-methyl-ribofuranose;   β-1-{[4-((2S)-((2S)-Aminopropionylamino)-2-carboxy)ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-((2S)-((2S)-Amino-3,3-dimethylbutyroylamino)-2-carboxy)ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-((2S)-(Aminoacetylamino)-2-carboxy)ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-((2S)-((2S)-Aminophenacetylamino)-2-carboxy)ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-((2S)-(2-Amino-2-methylpropionylamino)-2-carboxy)ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-((2S)-(1-Amino-cyclohexanecarbonylamino)-2-carboxy)ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-(4-(2-Acetoxyethoxy)carbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-(4-(2-Pivaloyloxyethoxy)carbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-(4-(2-Cyclohexanecarboxyethoxy)carbonylamino-2-oxo-1H-pyrimidin-1-yl)-2-C-methyl-ribofuranose;   β-1-{[4-(2-((2S)-Amino-3-methylbutyroylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((2S)-Amino-3-phenylpropionylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-(Phenyloxycarbonylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-β1}-2-C-methyl-ribofuranose;   β-1-{[4-(3-(Benzyloxycarbonylamino)-propoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-[4-(2-Dimethylamino-ethoxycarbonylamino)-2-oxo-1H-pyrimidin-1-yl]-2-C-methyl-ribofuranose;   β-1-[4-(4-Acetoxybutyroylamino)-2-oxo-1H-pyrimidin-1-yl]-2-C-methyl-ribofuranose;   β-1-[4-(4-Pivaloyloxybutyroylamino)-2-oxo-1H-pyrimidin-1-yl]-2-C-methyl-ribofuranose;   β-1-{[4-(2-((1-Pivaloyloxy-2,2-dimethylpropyl)oxycarbonylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((Isobutanoyloxymethyl)oxycarbonylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((Acetoxymethyl)oxycarbonylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((1-Isobutanoyloxyethyl)oxycarbonylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((1-Acetoxy-2-methylpropyl)oxycarbonylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((1-Isobutanoyloxy-2-methylpropyl)oxycarbonylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((1-Pivaloyloxy-2-methylpropypoxycarbonylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((1-Pivaloyloxyethyl)oxycarbonylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((1-Acetoxyethyl)oxycarbonylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((Acetoxymethyl)oxycarbonylmethylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((1-Isobutanoyloxyethyl)oxycarbonylmethylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((1-Acetoxy-2-methylpropyl)oxycarbonylmethylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((1-Isobutanoyloxy-2-methylpropyl)oxycarbonylmethylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((1-Pivaloyloxy-2-methylpropyl)oxycarbonylmethylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((1-Pivaloyloxyethyl)oxycarbonylmethylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((1-Acetoxyethyl)oxycarbonylmethylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((1-(2,6-Dimethylbenzoyl)oxymethyl)oxycarbonylmethylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((1-(2,6-Dimethylbenzoyl)oxy-2-methylpropyl)oxycarbonylmethylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose;   β-1-{[4-(2-((1-(2-Methylbenzoyl)oxy-2-methylpropyl)oxycarbonylmethylamino)-ethoxycarbonylamino]-2-oxo-1H-pyrimidin-1-yl}-2-C-methyl-ribofuranose; and   a pharmaceutically acceptable salt of any of the foregoing.