IP Library › Granted Patent US 9,370,569

Granted Patent B2

US 9,370,569 · App. 14/615,928 · Granted Jun 21, 2016

4′-difluoromethyl substituted nucleoside derivatives as inhibitors of influenza RNA replication

Inventors: Mark Smith (San Francisco, CA); Klaus G. Klumpp (West Chester, PA)

Assignee: Riboscience LLC

A61K45/06 A61K31/708 A61K31/7068 A61K31/7072 A61K31/7076 C07H19/06 C07H19/10 C07H19/16 C07H19/213

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Quick Facts

Patent No.: US 9,370,569
App. No.: 14/615,928
Granted: Jun 21, 2016
Kind: B2

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Abstract

The application discloses nucleoside derivatives of Formula I as inhibitors of Influenza RNA replication. In particular, the application discloses the use of purine and pyrimidine nucleoside derivatives of Formula I as inhibitors of Influenza RNA replication and pharmaceutical compositions containing such compounds.

Claims (1043)

1. A compound of Formula I

wherein:

Y is H or P(═X)(R′)(R);

R is O—R 1 or NHR 1′ ;

R 1′ is —C(R 2a )(R 2b )C(═O)OR 3 ;

R′ is N(R 4 )C(R 2a )(R 2b )C(═O)OR 3 , —OP(═O)(OH)OP(═O)(OH)OH, or —OR 3 ;

R 1 is H, lower haloalkyl, or aryl, wherein aryl is phenyl or naphthylenyl, optionally substituted with one or more lower alkyl, lower alkenyl, lower alkynyl, lower alkoxy, halo, lower haloalkyl, —N(R 1a ) 2 , acylamino, —SO 2 N(R 1a ) 2 , —C(═O)R 1b , —SO 2 (R 1c ), —NHSO 2 (R 1c ), nitro, cyano, or R 1″ ;

each R 1a is independently H or lower alkyl;

each R 1b is independently —OR 1a or —N(R 1a ) 2 ;

each R 1c is lower alkyl;

each R 2a and R 2b is independently H, lower alkyl, —(CH 2 ) r N(R 1a ) 2 , lower hydroxyalkyl, —CH 2 SH, —(CH 2 )S(O) p Me, —(CH 2 ) n NHC(═NH)NH 2 (1H-indol-3-yl)methyl, (1H-indol-4-yl)methyl, —(CH2) m C(═O)R 1b , aryl and aryl lower alkyl, wherein aryl is optionally substituted with one or more hydroxy, lower alkyl, lower alkoxy, halo, nitro or cyano;

m is 0, 1, or 2;

n is 1, 2, or 3;

p is 1 or 2;

r is 1 or 2;

or R 2a is H and R 2b and R 4 together form (CH 2 ) n ;

each R 3 is independently H, lower alkyl, lower haloalkyl, phenyl or phenyl lower alkyl, wherein phenyl and phenyl lower alkyl are optionally substituted with lower alkoxy;

or R 3 and R 1″ together form CH 2 ;

each R 4 is independently H, lower alkyl;

or R 2b and R 4 together form (CH 2 ) 3 ;

R w , R y , and R z are each independently H, OH or F;

R x is H, OH, or F;

or R 3 and R x together form a bond;

or R 1 and R x together form a bond;

X is O or S;

Base is uracil, cytosine, guanine, adenine, thymine, or heterocycloalkyl, each of which may optionally be substituted with one or more hydroxy, lower alkyl, lower alkoxy, halo, nitro or cyano;

with the proviso that if R w is H, R y is H, and R z is H, then R x is not H; and

with the proviso that Formula I is not ((2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-2-(difluoromethyl)-4-fluoro-3-hydroxytetrahydrofuran-2-yl)methyl tetrahydrogen triphosphate;

or a pharmacologically acceptable salt thereof.

2. The compound of claim 1 , wherein R W is H, R y is H, R x is OH, and R z is OH.

3. The compound of claim 1 , wherein R W is F, R y is H, R x is F, and R z is OH.

4. The compound of claim 1 , wherein R W is OH, R y is H, R x is H, and R z is OH.

5. The compound of claim 1 , wherein R W is F, R y is H, R x is H, and R z is OH.

6. The compound of claim 1 , wherein R W is H, R y is H, R x is F, and R z is OH.

7. The compound of claim 1 , wherein R W is H, R y is OH, R x is OH, and R z is H.

8. The compound of claim 1 , wherein R W is H, R y is F, R x is OH, and R z is F.

9. The compound of claim 1 , wherein R W is H, R y is F, R x is OH, and R z is H.

10. The compound of claim 1 , wherein R W is H, R y is H, R x is OH, and R z is F.

11. The compound of claim 1 , wherein X is O.

12. The compound of claim 1 , wherein X is S.

13. The compound of claim 1 , wherein R is O—R 1 , and R 1 is naphthylenyl.

14. The compound of claim 1 , wherein R′ is N(R 4 )C(R 2a )(R 2b )C(═O)OR 3 , R 4 is H, R 2a is H, R 2b is methyl, and R 3 is isopropyl.

15. A compound selected from the list consisting of:

4′-Difluoromethyluridine;

4′-Difluoromethyluridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyluridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyluridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyluridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyluridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyluridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyluridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate};

4′-Difluoromethyluridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate};

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-uridine;

4′-Difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-uridine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]uridine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]uridine;

4′-Difluoromethyluridine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethyluridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethyl-5-fluorouridine;

4′-Difluoromethyl-5-fluorouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluorouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-fluorouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluorouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-fluorouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluorouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyluridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate};

4′-Difluoromethyl5-fluorouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate};

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluorouridine;

4′-Difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluorouridine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-fluorouridine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-fluorouridine;

4′-Difluoromethyl-5-fluorouridine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethyl-5-fluorouridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethyl-5-chlorouridine;

4′-Difluoromethyl-5-chlorouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-chlorouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-chlorouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-chlorouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-chlorouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-chlorouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-chlorouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate};

4′-Difluoromethyl-5-chlorouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate};

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-chlorouridine;

4′-Difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-chlorouridine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-chlorouridine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-chlorouridine;

4′-Difluoromethyl-5-chlorouridine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethyl-5-chlorouridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethylcytidine;

4′-Difluoromethylcytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylcytidine-5′-(O-phenyl-N—(S)-1-(benzyloxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylcytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylcytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylcytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylcytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylcytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylcytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate};

4′-Difluoromethylcytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate};

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-cytidine;

4′-Difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-cytidine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]cytidine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]cytidine;

4′-Difluoromethylcytidine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethylcytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethyl-5-fluorocytidine;

4′-Difluoromethyl-5-fluorocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluorocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-fluorocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluorocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-fluorocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluorocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-fluorocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate};

4′-Difluoromethyl-5-fluorocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate};

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluorocytidine;

4′-Difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluorocytidine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-fluorocytidine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-fluorocytidine;

4′-Difluoromethyl-5-fluorcytidine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethyl-5-fluorocytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethyl-5-chlorocytidine;

4′-Difluoromethyl-5-chlorocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-chlorocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl5-chlorocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-chlorocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-chlorocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-chlorocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-chlorocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate};

4′-Difluoromethyl-5-chlorocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate};

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-chlorocytidine;

4′-Difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-chlorocytidine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-chlorocytidine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-chlorocytidine;

4′-Difluoromethyl-5-chlorocytidine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethyl-5-chlorocytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethyladenosine;

4′-Difluoromethyladenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyladenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyladenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyladenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyladenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyladenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyladenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

4′-Difluoromethyladenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-adenosine;

4′-Difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-adenosine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]adenosine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]adenosine;

4′-Difluoromethyladenosine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethyladenosine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethyl-7-adenosine;

4′-Difluoromethyl-7-adenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-7-adenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyladenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-7-adenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-7-adenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-7-adenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-7-adenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

4′-Difluoromethyl-7-adenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-7-adenosine;

4′-Difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-7-adenosine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-7-adenosine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]adenosine;

4′-Difluoromethyl-7-adenosine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethyl-7-adenosine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethylguanosine;

4′-Difluoromethylguanosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylguanosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylguanosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylguanosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylguanosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylguanosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylguanosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

4′-Difluoromethylguanosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-guanosine;

4′-Difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-guanosine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]guanosine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]guanosine;

4′-Difluoromethylguanosine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethylguanosine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethyluridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyluridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyluridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyluridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyluridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyluridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyluridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyluridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyluridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-uridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-uridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]uridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]uridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyluridine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethyluridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorouridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyluridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluorouridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluorouridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-fluorouridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-uridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorouridine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorouridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorouridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-chlorouridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-chlorouridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-chlorouridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-chlorouridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorouridine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorouridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethylcytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethylcytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylcytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylcytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylcytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylcytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylcytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylcytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylcytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-cytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-cytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]cytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]cytidine;

2′-Deoxy-4′-difluoromethyl-2′-fluorocytidine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-4′-difluoromethyl-2′-fluorocytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorocytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylcytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluorocytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluorocytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-fluorocytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-cytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorocytidine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-fluorocytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorocytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-chlorocytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-chlorocytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-chlorocytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-chlorocytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorocytidine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5-chlorocytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethyladenosine;

2′-Deoxy-2′-fluoro-4′-difluoromethyladenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyladenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyladenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyladenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyladenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyladenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyladenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyladenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-adenosine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-adenosine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]adenosine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]adenosine;

2′-Deoxy-4′-difluoromethyl-2′-fluoroadenosine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-4′-difluoromethyl-2′-fluoroadenosine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethyladenosine;

2′-Deoxy-2′-fluoro-4′-difluoromethylguanosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyguanosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylguanosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylguanosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylguanosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylguanosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylguanosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylguanosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-guanosine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-guanosine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]guanosine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]guanosine;

2′-Deoxy-4′-difluoromethyl-2′-fluoroguanosine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-4′-difluoromethyl-2′-fluoroguanosine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethylarauridine;

2′-Deoxy-2′-fluoro-4′-difluoromethylarauridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyarauridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylarauridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylarauridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylarauridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylarauridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylarauridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylarauridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-arauridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-arauridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]arauridine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]arauridine;

2′-Deoxy-4′-difluoromethyl-2′-fluoroarauridine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-4′-difluoromethyl-2′-fluoroarauridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylarauridine;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylarauridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylarauridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylarauridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylarauridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylarauridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylarauridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylarauridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylarauridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′,5-difluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-arauridine;

2′-Deoxy-2′,5-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-arauridine;

2′-Deoxy-2′,5-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-arauridine;

2′-Deoxy-2′,5-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-arauridine;

2′-Deoxy-4′-difluoromethyl-2′,5-difluoroarauridine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-4′-difluoromethyl-2′,5-difluoroarauridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylarauridine;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylarauridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylarauridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylarauridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylarauridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylarauridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylarauridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylarauridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylarauridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-arauridine;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-arauridine;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-arauridine;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-arauridine;

4-Chloro-2′-deoxy-4′-difluoromethyl-2′-fluoroarauridine-3′,5′-cyclic phosphoric acid isopropyl ester;

4-Chloro-2′-deoxy-4′-difluoromethyl-2′-fluoroarauridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethylaracytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethylaracytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethlaracytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaracytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaracytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaracytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaracytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaracytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaracytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-aracytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-aracytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]aracytidine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]aracytidine;

2′-Deoxy-4′-difluoromethyl-2′-fluoroaracytidine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-4′-difluoromethyl-2′-fluoroaracytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylaracytidine;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylaracytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylaracytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylaracytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylaracytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylaracytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylaracytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylaracytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′,5-difluoro-4′-difluoromethylaracytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′,5-difluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-aracytidine;

2′-Deoxy-2′,5-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-aracytidine;

2′-Deoxy-2′,5-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-aracytidine;

2′-Deoxy-2′,5-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-aracytidine;

2′-Deoxy-4′-difluoromethyl-2′,5-difluoroaracytidine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-4′-difluoromethyl-2′,5-difluoroaracytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4-Chloro-2′-deoxy-2′fluoro-4′-difluoromethylaracytidine;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylaracytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylaracytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylaracytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylaracytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylaracytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylaracytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylaracytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylaracytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-aracytidine;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-aracytidine;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-aracytidine;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-aracytidine;

4-Chloro-2′-deoxy-4′-difluoromethyl-2′-fluoroaracytidine-3′,5′-cyclic phosphoric acid isopropyl ester;

4-Chloro-2′-deoxy-4′-difluoromethyl-2′-fluoroaracytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethylaraadenosine;

2′-Deoxy-2′-fluoro-4′-difluoromethylaraadenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethlaraadenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaraadenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaraadenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaraadenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaraadenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate 2′-Deoxy-2′-fluoro-4′-difluoromethylaraadenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaraadenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-araadenosine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-araadenosine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]araadenosine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]araadenosine;

2′-Deoxy-4′-difluoromethyl-2′-fluoroaraadenosine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-4′-difluoromethyl-2′-fluoroaraadenosine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′-fluoro-4′-difluoromethylaraguanosine;

2′-Deoxy-2′-fluoro-4′-difluoromethylaraguanosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethlaraguanosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaraguanosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaraguanosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaraguanosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaraguanosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaraguanosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethylaraguanosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-araguanosine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-araguanosine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]araguanosine;

2′-Deoxy-2′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]araguanosine;

2′-Deoxy-4′-difluoromethyl-2′-fluoroaraguanosine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-4′-difluoromethyl-2′-fluoroaraguanosine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyluridine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyluridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyluridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyluridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyluridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyluridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyluridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyluridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyluridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-uridine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-uridine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]uridine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]uridine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyluridine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Dideoxy-2′-difluoro-4′-difluoromethyluridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorouridine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Dideoxy-2′-difluoro-4′-difluoromethyl-5-fluorouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluorouridine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluorouridine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-fluorouridine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-uridine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorouridine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorouridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-chlorouridine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-chlorouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-chlorouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-chlorouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-chlorouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-chlorouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-chlorouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-chlorouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-chlorouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-chlorouridine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-chlorouridine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-chlorouridine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-chlorouridine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-chlorouridine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-chlorouridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylcytidine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-cytidine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-cytidine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]cytidine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]cytidine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylcytdine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorocytidine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluoroucytidine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluorocytidine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-fluorocytidine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-cytidine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorocytidine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5-fluorocytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

5-Chloro-2′-deoxy-2′,2′-difluoro-4′-difluoromethylcytidine;

5-Chloro-2′-deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-2′-deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-2′-deoxy-2,2″-difluoro-4′-difluoromethylcytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-2′-deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-2′-deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-2′-deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-2′-deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

5-Chloro-2′-deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

5-Chloro-2′-deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)cytidine;

5-Chloro-2′-deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)cytidine;

5-Chloro-2′-deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]cytidine;

5-Chloro-2′-deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]cytidine;

5-Chloro-2′-deoxy-2′,2′-difluoro-4′-difluoromethylcytidine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-2′,2′-fluoro-4′-difluoromethylcytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′2′-difluoro-4′-difluoromethyladenosine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyladenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyladenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyladenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyladenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyladenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyladenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyladenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyladenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-adenosine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-adenosine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]adenosine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]adenosine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyladenosine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyladenosine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylguanosine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylguanosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylguanosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylguanosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylguanosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylguanosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylguanosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylguanosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylguanosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylguanosine-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-cytidine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylguanosine-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-cytidine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]guanosine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]guanosine;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylguanosine-3′,5′-cyclic phosphoric acid isopropyl ester;

2′-Deoxy-2′,2′-difluoro-4′-difluoromethylguanosine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethylarauridine;

4′-Difluoromethylarauridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethlarauridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylarauridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylarauridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylarauridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylarauridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylarauridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate};

4′-Difluoromethylarauridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate};

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-arauridine;

4′-Difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-arauridine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]arauridine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]arauridine;

4′-Difluoromethylarauridine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethylarauridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethyl-5-fluoroarauridine;

4′-Difluoromethyl-5-fluoroarauridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluoroarauridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-fluoroarauridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluoroarauridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate

4′-Difluoromethyl-5-fluoroarauridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate

4′-Difluoromethyl-5-fluoroarauridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate

4′-difluoromethyl-5-fluoroarauridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

4′-Difluoromethyl-5-fluoroarauridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluoroarauridine;

2′-Deoxy-2′,5-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluoroarauridine;

2′-Deoxy-2′,5-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-fluoroarauridine;

2′-Deoxy-2′,5-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-fluoroarauridine;

4′-Difluoromethyl-5-fluoroarauridine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethyl-5-fluoroarauridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

5-Chloro-4′-difluoromethylarauridine;

5-Chloro-4′-difluoromethylarauridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-4′-difluoromethylarauridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-4′-difluoromethylarauridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylarauridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-4′-difluoromethylarauridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-4′-difluoromethylarauridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-4′-difluoromethylarauridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

5-Chloro-4′-difluoromethylarauridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

5-Chloro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-arauridine;

5-Chloro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-arauridine;

5-Chloro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-arauridine;

5-Chloro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-arauridine;

5-Chloro-4′-difluoromethylarauridine-3′,5′-cyclic phosphoric acid isopropyl ester;

5-Chloro-4′-difluoromethylarauridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethylaracytidine;

4′-Difluoromethylaracytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethlaracytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylaracytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylaracytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylaracytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylaracytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylaracytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

4′-Difluoromethylaracytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-aracytidine;

4′-Difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-aracytidine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]aracytidine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]aracytidine;

4′-Difluoromethylaracytidine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethylaracytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethyl-5-fluoroaracytidine;

4′-Difluoromethyl-5-fluoroaracytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluoroaracytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-fluoroaracytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluoroaracytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-fluoroaracytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluoroaracytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-difluoromethyl-5-fluoroaracytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

4′-Difluoromethyl-5-fluoroaracytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluoroaracytidine;

2′-Deoxy-2′,5-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluoroaracytidine;

2′-Deoxy-2′,5-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-fluoroaracytidine;

2′-Deoxy-2′,5-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-fluoroaracytidine;

4′-Difluoromethyl-5-fluoroaracytidine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethyl-5-fluoroaracytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

5-Chloro-4′-difluoromethylaracytidine;

5-Chloro-4′-difluoromethylaracytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-4′-difluoromethylaracytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-4′-difluoromethylaracytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4-Chloro-2′-deoxy-2′-fluoro-4′-difluoromethylaracytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-4′-difluoromethylaracytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-4′-difluoromethylaracytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-4′-difluoromethylaracytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

5-Chloro-4′-difluoromethylaracytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

5-Chloro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-aracytidine;

5-Chloro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-aracytidine;

5-Chloro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-aracytidine;

5-Chloro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-aracytidine;

5-Chloro-4′-difluoromethylaracytidine-3′,5′-cyclic phosphoric acid isopropyl ester;

5-Chloro-4′-difluoromethylaracytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethylaraadenosine;

4′-Difluoromethylaraadenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethlaraadenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylaraadenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylaraadenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylaraadenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylaraadenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylaraadenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

4′-Difluoromethylaraadenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-araadenosine;

4′-Difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-araadenosine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]araadenosine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]araadensoine;

4′-Difluoromethylaraadenosine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethylaraadenosine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethylaraguanosine;

4′-Difluoromethylaraguanosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethlaraadenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylaraguanosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylaraguanosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylaraguanosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylaraguanosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylaraguanosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

4′-Difluoromethylaraguanosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-araguanosine;

4′-Difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-araguanosine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]araguanosine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]araguanosine;

4′-Difluoromethylaraguanosine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethylaraguanosine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

3′-Deoxy-3′-fluoro-4′-difluoromethyluridine;

3′-Deoxy-3′-fluoro-4′-difluoromethyluridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethyluridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethyluridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethyluridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethyluridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethyluridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethyluridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

3′-Deoxy-3′-fluoro-4′-difluoromethyluridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-uridine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-uridine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]uridine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]uridine;

3′-Deoxy-3′-fluoro-4′-difluoromethylcytidine;

3′-Deoxy-3′-fluoro-4′-difluoromethylcytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylcytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylcytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylcytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylcytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylcytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylcytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylcytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-cytidine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-cytidine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]cytidine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]cytidine;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylouridine;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylouridine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylouridine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xylouridine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xylouridine;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylouridine;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

3′-Deoxy-3′,5-difluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylouridine;

3′-Deoxy-3′,5-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylouridine;

3′-Deoxy-3′,5-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xylouridine;

3′-Deoxy-3′,5-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xylouridine;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylouridine;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylouridine;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylouridine;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xylouridine;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xylouridine;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylocytidine;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxylocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylocytidine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylocytidine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xylocytidine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xylocytidine;

3′-Deoxy-3′5-difluoro-4′-difluoromethylxylocytidine;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

3′-Deoxy-3′,5-difluoro-4′-difluoromethylxylocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

3′-Deoxy-3′,5-difluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylocytidine;

3′-Deoxy-3′,5-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylocytidine;

3′-Deoxy-3′,5-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xylocytidine;

3′-Deoxy-3′,5-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xylocytidine;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylocytidine;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethylxylocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylocytidine;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylocytidine;

5-Chloro-3′-deoxy-3′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xylocytidine;

5-Chloro-3′-deoxy 3′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xylocytidine;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloadenosine;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloadenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloadenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloadenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloadenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloadenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloadenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloadenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloadenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xyloadenosine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xyloadenosine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xyloadenosine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xyloadenosine;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloguanosine;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloguanosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloguanosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloguanosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloguanosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloguanosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloguanosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloguanosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

3′-Deoxy-3′-fluoro-4′-difluoromethylxyloguanosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xyloguanosine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xyloguanosine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xyloguanosine;

3′-Deoxy-3′-fluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xyloguanosine;

4′-Difluoromethylxylouridine;

4′-Difluoromethylxylouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylxylouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylxylouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylxylouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylxylouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylxylouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylxylouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

4′-Difluoromethylxylouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylouridine;

4′-Difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylouridine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xylouridine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xylouridine;

4′-Difluoromethylxylouridine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethylxylouridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethyl-5-fluoroxylouridine;

4′-Difluoromethyl-5-fluoroxylouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluororxylouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-fluoroxylouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluoroxylouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-fluoroxylouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluoroxylouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-fluoroxylouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

4′-Difluoromethyl-5-fluororxylouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluoroxylouridine;

4′-Difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluoroxylouridine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-fluoroxylouridine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-fluororxylouridine;

4′-Difluoromethyl-5-fluoroxylouridine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethyl-5-fluoroxylouridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

5-Chloro-4′-difluoromethylxylouridine;

5-Chloro-4′-difluoromethylxylouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-4′-difluoromethylxylouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-4′-difluoromethylxylouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-4′-difluoromethylxylouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-4′-difluoromethylxylouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-4′-difluoromethylxylouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-4′-difluoromethylxylouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

5-Chloro-4′-difluoromethylxylouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

5-Chloro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylouridine;

5-Chloro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylouridine;

5-Chloro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xylouridine;

5-Chloro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xylouridine;

5-Chloro-4′-difluoromethylxylouridine-3′,5′-cyclic phosphoric acid isopropyl ester;

5-Chloro-4′-difluoromethylxylouridine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethylxylocytidine;

4′-Difluoromethylxylocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylxylocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylxylocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylxylocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylxylocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylxylocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylxylocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

4′-Difluoromethylxylocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xylocytidine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xylocytidine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xylocytidine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xylocytidine;

4′-Difluoromethylxylocytidine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethylxylocytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethyl-5-fluoroxylocytidine;

4′-Difluoromethyl-5-fluoroxylocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluororxylocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-fluoroxylocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluoroxylocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-fluoroxylocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethyl-5-fluoroxylocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethyl-5-fluoroxylocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

4′-Difluoromethyl-5-fluororxylocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

4′-Difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluoroxylocytidine;

4′-Difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluoroxylocytidine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-fluoroxylocytidine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-fluororxylocytidine;

4′-Difluoromethyl-5-fluoroxylouridine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethyl-5-fluoroxylocytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

5-Chloro-4′-difluoromethylxylocytidine;

5-Chloro-4′-difluoromethylxylocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-4′-difluoromethylxylocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-4′-difluoromethylxylocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-4′-difluoromethylxylocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-4′-difluoromethylxylocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-4′-difluoromethylxylocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-4′-difluoromethylxylocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

5-Chloro-4′-difluoromethylxylocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

5-Chloro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylocytidine;

5-Chloro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-xylocytidine;

5-Chloro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xylocytidine;

5-Chloro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xylocytidine;

5-Chloro-4′-difluoromethylxylocytidine-3′,5′-cyclic phosphoric acid isopropyl ester;

5-Chloro-4′-difluoromethylxylocytidine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethylxyloadenosine;

4′-Difluoromethylxyloadenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl; phosphoramidate;

4′-Difluoromethylxyloadenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylxyloadenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylxyloadenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylxyloadenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylxyloadenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylxyloadenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

4′-Difluoromethylxyloadenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xyloadenosine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xyloadenosine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xyloadenosine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xyloadenosine;

4′-Difluoromethylxyloadenosine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethylxyloadenosine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

4′-Difluoromethylxyloguanosine;

4′-Difluoromethylxyloguanosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylxyloguanosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylxyloguanosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylxyloguanosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylxyloguanosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

4′-Difluoromethylxyloguanosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

4′-Difluoromethylxyloguanosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

4′-Difluoromethylxyloguanosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xyloguanosine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xyloguanosine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]xyloguanosine;

4′-Difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]xyloguanosine;

4′-Difluoromethylxyloguanosine-3′,5′-cyclic phosphoric acid isopropyl ester;

4′-Difluoromethylxyloguanosine-3′,5′-cyclic thiophosphoric acid isopropyl ester;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyluridine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-uridine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-uridine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]uridine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]uridine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluorouridine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluorouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluorouridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluorouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluorouridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluorouridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluororuridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluororuridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluorouridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluorouridine-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-uridine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluorouridine-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-uridine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-fluorouridine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-fluorouridine;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethyluridine;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-uridine;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethyluridine-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-uridine;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]uridine;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]uridine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylcytidine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-cytidine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-cytidine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]cytidine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]cytidine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluorocytidine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluorocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluorocytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluorocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluorocytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluorocytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluororcytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluororcytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5-fluorocytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluorocytidine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethy-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-5-fluorocytidine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]-5-fluorocytidine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]-5-fluorocytidine;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethylcytidine;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-uridine;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-uridine;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]cytidine;

5-Chloro-3′-deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]cytidine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyladenosine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylcytidine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyladenosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyladenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyladenosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyladenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyladenosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyladenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyladenosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-adenosine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-adenosine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]adenosine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]adenosine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylguanosine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylguanosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylguanosine-5′-(O-phenyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylguanosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylguanosine-5′-(O-1-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylguanosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl phosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylguanosine-5′-(O-2-naphthyl-N—(S)-1-(isopropoxycarbonyl)ethyl thiophosphoramidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylguanosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]phosphorodiamidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethylguanosine-5′-{N,N′-bis[(S)-1-(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-(2-oxido-4-H-1,3,2-benzodioxaphosphorin-2-yl)-guanosine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-(2-sulfide-4-H-1,3,2-benzodioxaphosphorin-2-yl)-guanosine;

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)phosphinyl]guanosine; and

3′-Deoxy-3′,3′-difluoro-4′-difluoromethyl-5′-O-[bis(4-methoxyphenoxy)thiophosphinyl]guanosine.

16. A method of treating Influenza comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 1 .

17. A composition comprising the compound of claim 1 , admixed with at least one carrier, diluent or excipient.

18. A composition comprising the compound of claim 1 in combination with one or more antiviral compounds.

19. A method for treating an Influenza infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of Formula I

wherein:

Y is H or P(═X)(R′)(R);

R is O—R 1 or NHR 1′ ;

R 1′ is —C(R 2a )(R 2b )C(═O)OR 3 ;

R′ is N(R 4 )C(R 2a )(R 2b )C(═O)OR 3 , —OP(═O)(OH)OP(═O)(OH)OH, or —OR 3 ;

each R 1a is independently H or lower alkyl;

each R 1b is independently —OR 1a or —N(R 1a ) 2 ;

each R 1c is lower alkyl;

each R 2a and R 2b is independently H, lower alkyl, —(CH 2 ) r N(R 1a ) 2 , lower hydroxyalkyl, —CH 2 SH, —(CH 2 )S(O) p Me, —(CH 2 ) n NHC(═NH)NH 2 , (1H-indol-3-yl)methyl, (1H-indol-4-yl)methyl, —(CH2) m C(═O)R 1b , aryl and aryl lower alkyl, wherein aryl is optionally substituted with one or more hydroxy, lower alkyl, lower alkoxy, halo, nitro or cyano;

m is 0, 1, or 2;

n is 1, 2, or 3;

p is 1 or 2;

r is 1 or 2;

or R 2a is H and R 2b and R 4 together form (CH 2 ) n ;

each R 3 is independently H, lower alkyl, lower haloalkyl, phenyl or phenyl lower alkyl, wherein phenyl and phenyl lower alkyl are optionally substituted with lower alkoxy;

or R 3 and R 1″ together form CH 2 ;

each R 4 is independently H, lower alkyl;

or R 2b and R 4 together form (CH 2 ) 3 ;

R w , R y , and R z are each independently H, OH or F;

R x is H, OH, or F;

or R 3 and R x together form a bond;

or R 1 and R x together form a bond;

X is O or S; and

Base is uracil, cytosine, guanine, adenine, thymine, or heterocycloalkyl, each of which may optionally be substituted with one or more hydroxy, lower alkyl, lower alkoxy, halo, nitro or cyano;

or a pharmacologically acceptable salt thereof.

20. A method for treating an Influenza infection comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 15 .

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 13, 2017

From: SMITH, MARK; KLUMPP, KLAUS G.

To: RIBOSCIENCE LLC

Reel/Frame 041553/0548 →

Continuity (2)

Provisional Application 61936569 · Feb 6, 2014

Related Publication 20150225441A1 · Aug 13, 2015