NZ723551B2 - 4'-difluoromethyl substituted nucleoside derivatives as inhibitors of influenza rna replication - Google Patents

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. g such compounds.

Description

’-DIFLUOROMETHYL SUBSTITUTED NUCLEOSIDE DERIVATIVES AS INHIBITORS OF INFLUENZA RNA REPLICATION FIELD OF THE INVENTION The invention relates to nucleoside derivatives as inhibitors of Influenza RNA replication. In particular, the invention is concerned with the use of purine and pyrimidine nucleoside derivatives as inhibitors of Influenza RNA replication and pharmaceutical compositions containing such compounds.

Influenza virus is causing seasonal epidemics of respiratory disease throughout the world. Approved treatment options for Influenza infection fall into two classes, neuraminidase inhibitors (Oseltamivir, Zanamivir) and M2 inhibitors (Amantadine, Rimantadine). However, the yearly influenza epidemics are still associated with a significant number of excess deaths every year. The occurrence of yearly deaths due to influenza and pneumonia correlates with circulating influenza virus and with the relative pathogenicity of the particular circulating influenza strain.

In addition, new virus strains for which little or no population resistance exists can emerge through gene reassortment with viruses from a large animal reservoir and cause pandemics, which are a serious global public health issue. The available treatments of influenza virus infection have limited efficacy because of widespread resistance (amantadine, rimantadine) or requirement for early start of treatment (neuraminidase inhibitors). In addition, naturally resistant viruses have emerged that are resistant to both classes of inhibitors.

Many of the drugs approved for the treatment of viral infections are nucleosides or nucleoside analogues and most of these nucleoside analogue drugs inhibit viral replication, following conversion to the corresponding triphosphates, through inhibition of the viral polymerase enzymes. The influenza virus polymerase is essential for viral replication, and its inhibition by nucleoside triphosphate analogs results in the shut-down of virus production. Only very few nucleoside analogs have been previously found that can inhibit the influenza virus polymerase.

Influenza virus belongs to the family of Orthomyxoviridae. It is an RNA virus with a segmented negative sense RNA genome. The synthesis of viral messenger RNA and of viral genomic RNA in infected cells is performed by the trimeric influenza virus polymerase. Three virus encoded polymerase subunits (PA, PB1, PB2) and a virus encoded single stranded RNA binding protein (NP) are necessary and sufficient to perform RNA replication.

SUMMARY OF THE INVENTION The compounds of Formula I are useful for the treatment of Influenza infections, and for preparing pharmaceutical compositions comprising such compounds.

The invention provides a compound of Formula I Base wherein: Y is H or P(=X)(R’)(R); 1 1’ R is O-R or NHR ; 1’ 2a 2b 3 R is -C(R )(R )C(=O)OR ; 4 2a 2b 3 3 R’ is N(R )C(R )(R )C(=O)OR , –OP(=O)(OH)OP(=O)(OH)OH, or –OR ; R 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, 1a 1a 1b 1c 1c halo, lower haloalkyl, -N(R ) , acylamino, -SO N(R ) , -C(=O)R , -SO (R ), -NHSO (R ), 2 2 2 2 2 nitro, cyano, or R ; each R is independently H or lower alkyl; 1b 1a 1a each R is independently -OR or -N(R ) ; each R is lower alkyl; 2a 2b 1a each R and R is independently H, lower alkyl, -(CH ) N(R ) , 2 r 2 lower hydroxyalkyl, -CH SH, -(CH )S(O) Me, -(CH ) NHC(=NH)NH , (1H-indolyl)methyl, 2 2 p 2 n 2 (1H-indolyl)methyl, -(CH2) C(=O)R , 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; 2a 2b 4 or R is H and R and R together form (CH ) ; each R is independently H, lower alkyl, lower haloalkyl, phenyl or phenyl lower alkyl, wherein phenyl and phenyl lower alkyl are optionally substituted with lower alkoxy; 3 1’’ or R and R together form CH ; each R is independently H, lower alkyl; 2b 4 or R and R together form (CH ) ; w y z R , R , and R are each independently H, OH or F; R is H, OH, or F; or R and R together form a bond; or R and R together form a bond; X is O or S; Base is uracil, cytosine, guanine, adenine, or thymine, , 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 Rw is H, Ry is H, and Rz is H, then Rz is not H; or a pharmacologically acceptable salt thereof.

The invention provides a compound of Formula I of the inventionfor use as a therapeutically active substance, or for the treatment or prophylaxis of Influenza infection. [0007a] The invention also provides a pharmaceutical composition comprising a compound of Formula I of the invention, and a therapeutically inert carrier. [0007b] The invention also provides a pharmaceutical composition of the invention for use in the treatment or prophylaxis of Influenza infection.

Also described is 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 or a compound resulting in the formation of a compound of Formula I in vivo.

The invention also relates to use of a compound of Formula I of the invention in the manufacture of a medicament for the treatment or prophylaxis of Influenza infection.

DETAILED DESCRIPTION OF THE INVENTION The compounds of Formula I have been shown to be inhibitors of the influenza virus RNA polymerase or result in the formation of inhibitors of the influenza virus polymerase after metabolic conversion in human cells.

The term "alkyl" as used herein denotes a straight or branched chain hydrocarbon residue containing 1 to 12 carbon atoms. Preferably, the term "alkyl" denotes a straight or branched chain hydrocarbon residue containing 1 to 7 carbon atoms. Most preferred are methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, tert. -butyl or pentyl. The alkyl may be unsubstituted or substituted. The substituents are selected from one or more of cycloalkyl, nitro, amino, alkyl amino, dialkyl amino, alkyl carbonyl and cycloalkyl carbonyl.

The term "cycloalkyl" as used herein denotes an optionally substituted cycloalkyl group containing 3 to 7 carbon atoms, e. g. cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.

The term "alkoxy" as used herein denotes an optionally substituted straight or branched chain alkyl-oxy group wherein the "alkyl" portion is as defined above such as methoxy, ethoxy, n-propyloxy, i-propyloxy, n-butyloxy, i-butyloxy, tert. -butyloxy, pentyloxy, hexyloxy, heptyloxy including their isomers.

The term "alkoxyalkyl" as used herein denotes an alkoxy group as defined above which is bonded to an alkyl group as defined above. Examples are methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, propyloxypropyl, methoxybutyl, ethoxybutyl, propyloxybutyl, butyloxybutyl, tert. -butyloxybutyl, methoxypentyl, ethoxypentyl, propyloxypentyl including their isomers.

The term "alkenyl" as used herein denotes an unsubstituted or substituted hydrocarbon chain radical having from 2 to 7 carbon atoms, preferably from 2 to 4 carbon atoms, and having one or two olefinic double bonds, preferably one olefinic double bond. Examples are vinyl, 1- propenyl, 2-propenyl (allyl) or 2-butenyl (crotyl).

The term "alkynyl" as used herein denotes to unsubstituted or substituted hydrocarbon chain radical having from 2 to 7 carbon atoms, preferably 2 to 4 carbon atoms, and having one or where possible two triple bonds, preferably one triple bond. Examples are ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl or 3-butynyl.

The term "H" as used herein refers to hydrogen, including deuterium.

The term "hydroxyalkyl" as used herein denotes a straight or branched chain alkyl group as defined above wherein 1, 2, 3 or more hydrogen atoms are substituted by a hydroxy group. Examples are hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, 1-hydroxypropyl, 2- hydroxypropyl, 3-hydroxypropyl, hydroxyisopropyl, hydroxybutyl and the like.

The term "haloalkyl" as used herein denotes a straight or branched chain alkyl group as defined above wherein 1, 2, 3 or more hydrogen atoms are substituted by a halogen.

Examples are 1-fluoromethyl, 1-chloromethyl, 1-bromomethyl, 1-iodomethyl, trifluoromethyl, trichloromethyl, tribromomethyl, triiodomethyl, 1-fluoroethyl, 1-chloroethyl, 1-bromoethyl, 1- iodoethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2-dichloroethyl, 3- bromopropyl or 2,2,2-trifluoroethyl and the like.

The term "alkylthio" as used herein denotes a straight or branched chain (alkyl)S- group wherein the "alkyl" portion is as defined above. Examples are methylthio, ethylthio, n- propylthio, i-propylthio, n-butylthio, i-butylthio or tert.-butylthio.

The term "aryl" as used herein denotes an optionally substituted phenyl and naphthyl (also referred to as naphthylenyl") (e. g. 1-naphthyl, 2-naphthyl or 3-naphthyl). Suitable substituents for aryl can be selected from those named for alkyl, in addition however, halogen, hydroxy and optionally substituted alkyl, haloalkyl, alkenyl, alkynyl and aryloxy are substituents which can be added to the selection.

The term "heterocyclyl" or "heterocycloalkyl" or "heterocycle" as used herein denotes an optionally substituted saturated, partially unsaturated or aromatic monocyclic, bicyclic or tricyclic heterocyclic systems which contain one or more hetero atoms selected from nitrogen, oxygen and sulfur which can also be fused to an optionally substituted saturated, partially unsaturated or aromatic monocyclic carbocycle or heterocycle.

Examples of suitable heterocycles are oxazolyl, isoxazolyl, furyl, tetrahydrofuryl, 1,3- dioxolanyl, dihydropyranyl, 2-thienyl, 3-thienyl, pyrazinyl, isothiazolyl, dihydrooxazolyl, pyrimidinyl, tetrazolyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl, pyrrolidinonyl, (N-oxide)- pyridinyl, 1-pyrrolyl, 2-pyrrolyl, triazolyl e. g. 1,2,3-triazolyl or 1,2,4-triazolyl, 1-pyrazolyl, 2- pyrazolyl, 4-pyrazolyl, piperidinyl, morpholinyl (e. g. 4-morpholinyl), thiomorpholinyl (e. g. 4- thiomorpholinyl), thiazolyl, pyridinyl, dihydrothiazolyl, imidazolidinyl, pyrazolinyl, piperazinyl, 1-imidazolyl, 2-imidazolyl, 4-imidazolyl, thiadiazolyl e. g. 1,2,3-thiadiazolyl, 4- methylpiperazinyl, 4-hydroxypiperidinyl.

Suitable substituents for heterocycloalkyls can be selected from those named for alkyl, in addition however, optionally substituted alkyl, alkenyl, alkynyl, an oxo group (=O) or aminosulphonyl are substituents which can be added to the selection.

The term "acyl" ("alkylcarbonyl")as used herein denotes a group of formula C(=O)R wherein R is hydrogen, an unsubstituted or substituted straight or branched chain hydrocarbon residue containing 1 to 7 carbon atoms or a phenyl group. Most preferred acyl groups are those wherein R is hydrogen, an unsubstituted straight chain or branched hydrocarbon residue containing 1 to 4 carbon atoms or a phenyl group.

The term "halogen" or "halo" stands for fluorine, chlorine, bromine or iodine, preferable fluorine, chlorine, bromine.

In the pictorial representation of the compounds given throughout this application, a thickened tapered line ( ) indicates a substituent which is above the plane of the ring to which the asymmetric carbon belongs and a dotted line ( ) indicates a substituent which is below the plane of the ring to which the asymmetric carbon belongs.

Compounds of formula I may exhibit stereoisomerism. These compounds can be any isomer of the compound of formula I or mixtures of these isomers. The compounds and intermediates of the present invention having one or more asymmetric carbon atoms may be obtained as racemic mixtures of stereoisomers which can be resolved.

Compounds of formula I may exhibit tautomerism which means that the compounds of this invention can exist as two or more chemical compounds that are capable of facile interconversion. In many cases it merely means the exchange of a hydrogen atom between two other atoms, to either of which it forms a covalent bond. Tautomeric compounds exist in a mobile equilibrium with each other, so that attempts to prepare the separate substances usually result in the formation of a mixture that shows all the chemical and physical properties to be expected on the basis of the structures of the components.

The most common type of tautomerism is that involving carbonyl, or keto, compounds and unsaturated hydroxyl compounds, or enols. The structural change is the shift of a hydrogen atom between atoms of carbon and oxygen, with the rearrangement of bonds. For example, in many aliphatic aldehydes and ketones, such as acetaldehyde, the keto form is the predominant one; in phenols, the enol form is the major component.

Compounds of formula I which are basic can form pharmaceutically acceptable salts with inorganic acids such as hydrohalic acids (e.g. hydrochloric acid and hydrobromic acid), sulphuric acid, nitric acid and phosphoric acid, and the like, and with organic acids (e.g. with acetic acid, tartaric acid, succinic acid, fumaric acid, maleic acid, malic acid, salicylic acid, citric acid, methanesulphonic acid and p-toluene sulphonic acid, and the like). The formation and isolation of such salts can be carried out according to methods known in the art.

Inhibitors of Influenza The application provides a compound of Formula I Base wherein: Y is H or P(=X)(R’)(R); 1 1’ R is O-R or NHR ; 1’ 2a 2b 3 R is -C(R )(R )C(=O)OR ; 4 2a 2b 3 3 R’ is N(R )C(R )(R )C(=O)OR , –OP(=O)(OH)OP(=O)(OH)OH, or –OR ; R 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, 1a 1a 1b 1c 1c halo, lower haloalkyl, -N(R ) , acylamino, -SO N(R ) , -C(=O)R , -SO (R ), -NHSO (R ), 2 2 2 2 2 nitro, cyano, or R ; each R is independently H or lower alkyl; 1b 1a 1a each R is independently -OR or -N(R ) ; each R is lower alkyl; 2a 2b 1a each R and R is independently H, lower alkyl, -(CH ) N(R ) , lower 2 r 2 hydroxyalkyl, -CH SH, -(CH )S(O) Me, -(CH ) NHC(=NH)NH , (1H-indolyl)methyl, (1H- 2 2 p 2 n 2 indolyl)methyl, -(CH2) C(=O)R , 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; 2a 2b 4 or R is H and R and R together form (CH ) ; each R is independently H, lower alkyl, lower haloalkyl, phenyl or phenyl lower alkyl, wherein phenyl and phenyl lower alkyl are optionally substituted with lower alkoxy; 3 1’’ or R and R together form CH ; each R is independently H, lower alkyl; 2b 4 or R and R together form (CH ) ; w y z R , R , and R are each independently H, OH or F; R is H, OH, or F; or R and R together form a bond; or R and R together form a bond; X is O or S; Base is uracil, cytosine, guanine, adenine, or thymine, 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 Rw is H, Ry is H, and Rz is H, then Rz is not H; or a pharmacologically acceptable salt thereof.

Described in one embodiment are compounds of Formula I as defined above, with the additional proviso that Formula I is not ((2R,3R,4R,5R)(4-aminooxopyrimidin-1(2H)-yl) (difluoromethyl)fluorohydroxytetrahydrofuranyl)methyl tetrahydrogen triphosphate or a pharmacologically acceptable salt thereof. [0032a] Also described is a compound of formula I wherein the base is heterocycloalkyl which may be substituted with one or more hydroxy, lower alkyl, lower alkoxy, halo, nitro or cyano.

The application provides the above compound of Formula I, wherein R is H, R is H, R is OH, and R is OH.

The application alternatively provides the above compound of Formula I, wherein R y x z is F, R is H, R is F, and R is OH.

The application alternatively provides the above compound of Formula I, wherein R y x z is OH, R is H, R is H, and R is OH.

The application alternatively provides the above compound of Formula I, wherein R y x z is F, R is H, R is H, and R is OH.

The application alternatively provides the above compound of Formula I, wherein R y x z is H, R is H, R is F, and R is OH.

The application alternatively provides the above compound of Formula I, wherein R y x z is H, R is OH, R is OH, and R is H.

The application alternatively provides the above compound of Formula I, wherein R y x z is H, R is F, R is OH, and R is F.

The application alternatively provides the above compound of Formula I, wherein R y x z is H, R is F, R is OH, and R is H.

The application alternatively provides the above compound of Formula I, wherein R y x z is H, R is H, R is OH, and R is F.

The application provides the compound of Formula I, wherein R is H.

The application provides the compound of Formula I, wherein R is OH.

The application provides the compound of Formula I, wherein R is H.

The application provides the compound of Formula I, wherein R is OH.

The application provides the compound of Formula I, wherein R’ is O-R , R is lower 1 1 x alkyl, R is –OR , and R and R together form a bond.

The application provides the compound of Formula I, wherein R is –OR , R is phenyl 1’’ 3 3 1’’ substituted with R , R’ is –OR , and R and R together form CH The application provides the compound of Formula I, wherein X is O.

The application provides the compound of Formula I, wherein X is S.

The application provides the compound of Formula I, wherein R is O-R , and R is phenyl optionally substituted with methoxy.

The application provides the compound of Formula I, wherein R is O-R , and R is naphthylenyl.

The application provides the compound of Formula I, wherein R’ is 4 2a 2b 3 4 2a 2b 3 N(R )C(R )(R )C(=O)OR , R is H, R is H, R is methyl, and R is isopropyl.

The application provides the compound of Formula I, wherein R’ is - OP(=O)(OH)OP(=O)(OH)OH.

The application provides the compound of Formula I, wherein Base is cytidine optionally substituted with halo.

The application provides the compound of Formula I, wherein Base is uridine optionally substituted with halo.

The application provides the compound of Formula I, wherein Base is guanosine.

The application provides the compound of Formula I, wherein Base is adenosine.

The application provides the compound of Formula I, wherein R is F if R is not H or The application provides the compound of Formula I, wherein R is F if R is not H or The application provides the compound of Formula I, wherein R is F if R is not H or y z The application provides the compound of Formula I, wherein both R and R are F if both R and R are not H or OH. y z The application provides the compound of Formula I, wherein R is H and R is OH if R is not OH or F and R is not H or F.

The application provides a compound selected from the list consisting of: 4’-Difluoromethyluridine; 4’-Difluoromethyluridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyluridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyluridine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate}; 4’-Difluoromethyluridine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate}; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-uridine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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’-Difluoromethylfluorouridine; 4’-Difluoromethylfluorouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluorouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluorouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluorouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluorouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluorouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyluridine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate}; 4’-Difluoromethyl5-fluorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate}; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)fluorouridine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)fluorouridine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] fluorouridine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] fluorouridine; 4’-Difluoromethylfluorouridine-3’,5’-cyclic phosphoric acid isopropyl ester; 4’-Difluoromethylfluorouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 4’-Difluoromethylchlorouridine; 4’-Difluoromethylchlorouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylchlorouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylchlorouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylchlorouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylchlorouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylchlorouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylchlorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate}; 4’-Difluoromethylchlorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate}; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)chlorouridine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)chlorouridine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl]chlorouridine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]chlorouridine; 4’-Difluoromethylchlorouridine-3’,5’-cyclic phosphoric acid isopropyl ester; 4’-Difluoromethylchlorouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 4’-Difluoromethylcytidine; 4’-Difluoromethylcytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylcytidine-5’-(O-phenyl-N-(S)(benzyloxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylcytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylcytidine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate}; 4’-Difluoromethylcytidine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate}; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-cytidine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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’-Difluoromethylfluorocytidine; 4’-Difluoromethylfluorocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluorocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate}; 4’-Difluoromethylfluorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate}; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)fluorocytidine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)fluorocytidine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] fluorocytidine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] fluorocytidine; 4’-Difluoromethylfluorcytidine-3’,5’-cyclic phosphoric acid isopropyl ester; 4’-Difluoromethylfluorocytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 4’-Difluoromethylchlorocytidine; 4’-Difluoromethylchlorocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylchlorocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyl5-chlorocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylchlorocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylchlorocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylchlorocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylchlorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate}; 4’-Difluoromethylchlorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate}; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)chlorocytidine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)chlorocytidine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] chlorocytidine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] chlorocytidine; 4’-Difluoromethylchlorocytidine-3’,5’-cyclic phosphoric acid isopropyl ester; 4’-Difluoromethylchlorocytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 4’-Difluoromethyladenosine; 4’-Difluoromethyladenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyladenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyladenosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethyladenosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-adenosine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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’-Difluoromethyladenosine; 4’-Difluoromethyladenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyladenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyladenosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethyladenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)adenosine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)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’-Difluoromethylguanosine; 4’-Difluoromethylguanosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylguanosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylguanosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylguanosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-guanosine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyluridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-uridine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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’-difluoromethylfluorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl) fluorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) fluorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl]fluorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]uridine; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-3’,5’-cyclic phosphoric acid isopropyl ester; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl) chlorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) chlorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl]chlorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]chlorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-3’,5’-cyclic phosphoric acid isopropyl ester; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-cytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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’-difluoromethylfluorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl) fluorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) fluorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl]fluorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]cytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-3’,5’-cyclic phosphoric acid isopropyl ester; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl) chlorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) chlorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl]chlorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] chlorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-3’,5’-cyclic phosphoric acid isopropyl ester; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- adenosine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyguanosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- guanosine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyarauridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- arauridine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylarauridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- arauridine; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorin yl)-arauridine; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorin 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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethlaracytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- aracytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylaracytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- aracytidine; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorin yl)-aracytidine; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorin 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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethlaraadenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraadenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraadenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraadenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraadenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’-difluoromethylaraadenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraadenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- araadenosine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethlaraguanosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- araguanosine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyluridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- uridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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’-difluoromethylfluorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Dideoxy-2’-difluoro-4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl) fluorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) fluorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] fluorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]uridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-3’,5’-cyclic phosphoric acid isopropyl ester; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl) chlorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) chlorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] chlorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] chlorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-3’,5’-cyclic phosphoric acid isopropyl ester; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylcytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- cytidine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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’-difluoromethylfluorocytidine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl) fluoroucytidine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) fluorocytidine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] fluorocytidine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]cytidine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-3’,5’-cyclic phosphoric acid isopropyl ester; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester; -Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethylcytidine; -Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethylcytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethylcytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-2’-deoxy-2,2’’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; -Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; -Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorin- 2-yl) cytidine; -Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2- benzodioxaphosphorinyl) cytidine; -Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] cytidine; -Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] cytidine; -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) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyladenosine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyladenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyladenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- adenosine; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-O-(2-oxidoH-1,3,2- benzodioxaphosphorinyl)-cytidine; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-O-(2-sulfideH-1,3,2- benzodioxaphosphorinyl)-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)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethlarauridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylarauridine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate}; 4’-Difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate}; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-arauridine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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’-Difluoromethylfluoroarauridine; 4’-Difluoromethylfluoroarauridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroarauridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethylfluoroarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethylfluoroarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate 4’-difluoromethylfluoroarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylfluoroarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)fluoroarauridine; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) fluoroarauridine; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] fluoroarauridine; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] fluoroarauridine; 4’-Difluoromethyl—5-fluoroarauridine-3’,5’-cyclic phosphoric acid isopropyl ester; 4’-Difluoromethylfluoroarauridine-3’,5’-cyclic thiophosphoric acid isopropyl ester; -Chloro-4’-difluoromethylarauridine; -Chloro-4’-difluoromethylarauridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-4’-difluoromethylarauridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-4’-difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; -Chloro -4’-difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; -Chloro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-arauridine; -Chloro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-arauridine; -Chloro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl]-arauridine; -Chloro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]-arauridine; -Chloro-4’-difluoromethylarauridine-3’,5’-cyclic phosphoric acid isopropyl ester; -Chloro-4’-difluoromethylarauridine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 4’-Difluoromethylaracytidine; 4’-Difluoromethylaracytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethlaracytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaracytidine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-aracytidine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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’-Difluoromethylfluoroaracytidine; 4’-Difluoromethylfluoroaracytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroaracytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-difluoromethylfluoroaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylfluoroaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)fluoroaracytidine; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) fluoroaracytidine; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] fluoroaracytidine; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] fluoroaracytidine; 4’-Difluoromethyl—5-fluoroaracytidine-3’,5’-cyclic phosphoric acid isopropyl ester; 4’-Difluoromethylfluoroaracytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester; -Chloro-4’-difluoromethylaracytidine; -Chloro-4’-difluoromethylaracytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-4’-difluoromethylaracytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-4’-difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; -Chloro -4’-difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; -Chloro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-aracytidine; -Chloro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-aracytidine; -Chloro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl]-aracytidine; -Chloro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]-aracytidine; -Chloro-4’-difluoromethylaracytidine-3’,5’-cyclic phosphoric acid isopropyl ester; -Chloro-4’-difluoromethylaracytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 4’-Difluoromethylaraadenosine; 4’-Difluoromethylaraadenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethlaraadenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaraadenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylaraadenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaraadenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylaraadenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaraadenosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylaraadenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-araadenosine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethlaraadenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaraguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylaraguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaraguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylaraguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaraguanosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylaraguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-araguanosine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyluridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-uridine; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylcytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-cytidine; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- xylouridine; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- xylouridine; 3’-Deoxy-3’,5-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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; -Chloro-3’-deoxy-3’-fluoro-4’-difluoromethylxylouridine; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorin yl)-xylouridine; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorin yl)-xylouridine; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] xylouridine; -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)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- xylocytidine; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- xylocytidine; 3’-Deoxy-3’,5-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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; -Chloro-3’-deoxy-3’-fluoro-4’-difluoromethylxylocytidine; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorin yl)-xylocytidine; -Chloro-3’-deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorin yl)-xylocytidine; -Chloro-3’-deoxy -3’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] xylocytidine; -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)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloadenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloadenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloadenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloadenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloadenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloadenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloadenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- xyloadenosine; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloguanosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- xyloguanosine; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxylouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxylouridine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-xylouridine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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’-Difluoromethylfluoroxylouridine; 4’-Difluoromethylfluoroxylouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluororxylouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylfluororxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)fluoroxylouridine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)fluoroxylouridine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl]fluoroxylouridine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]fluororxylouridine; 4’-Difluoromethylfluoroxylouridine-3’,5’-cyclic phosphoric acid isopropyl ester; 4’-Difluoromethylfluoroxylouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester; -Chloro-4’-difluoromethylxylouridine; -Chloro-4’-difluoromethylxylouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-4’-difluoromethylxylouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-4’-difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; -Chloro-4’-difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; -Chloro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-xylouridine; -Chloro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-xylouridine; -Chloro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] xylouridine; -Chloro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] xylouridine; -Chloro-4’-difluoromethylxylouridine-3’,5’-cyclic phosphoric acid isopropyl ester; -Chloro-4’-difluoromethylxylouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 4’-Difluoromethylxylocytidine; 4’-Difluoromethylxylocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxylocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxylocytidine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylxylocytidine-5’-{N,N’-bis[(S) (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’-Difluoromethylfluoroxylocytidine; 4’-Difluoromethylfluoroxylocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluororxylocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylfluororxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)fluoroxylocytidine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)fluoroxylocytidine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl]fluoroxylocytidine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]fluororxylocytidine; 4’-Difluoromethylfluoroxylouridine-3’,5’-cyclic phosphoric acid isopropyl ester; 4’-Difluoromethylfluoroxylocytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester; -Chloro-4’-difluoromethylxylocytidine; -Chloro-4’-difluoromethylxylocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-4’-difluoromethylxylocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-4’-difluoromethylxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; -Chloro-4’-difluoromethylxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; -Chloro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-xylocytidine; -Chloro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-xylocytidine; -Chloro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] xylocytidine; -Chloro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] xylocytidine; -Chloro-4’-difluoromethylxylocytidine-3’,5’-cyclic phosphoric acid isopropyl ester; -Chloro-4’-difluoromethylxylocytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 4’-Difluoromethylxyloadenosine; 4’-Difluoromethylxyloadenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl; phosphoramidate; 4’-Difluoromethylxyloadenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxyloadenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxyloadenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxyloadenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxyloadenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxyloadenosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylxyloadenosine-5’-{N,N’-bis[(S) (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)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxyloguanosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxyloguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxyloguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxyloguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxyloguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxyloguanosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylxyloguanosine-5’-{N,N’-bis[(S) (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)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyluridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- uridine; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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’-difluoromethylfluorouridine; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluororuridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluororuridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorouridine-5’-O-(2-oxidoH-1,3,2- benzodioxaphosphorinyl)-uridine; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorouridine-5’-O-(2-sulfideH-1,3,2- benzodioxaphosphorinyl)-uridine; 3’-Deoxy-3’,3’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] fluorouridine; 3’-Deoxy-3’,3’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] fluorouridine; -Chloro-3’-deoxy-3’,3’-difluoro-4’-difluoromethyluridine; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-O-(2-oxidoH-1,3,2- benzodioxaphosphorinyl)-uridine; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-O-(2-sulfideH-1,3,2- benzodioxaphosphorinyl)-uridine; -Chloro-3’-deoxy -3’,3’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] uridine; -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)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylcytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- cytidine; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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’-difluoromethylfluorocytidine; 3’-Deoxy-3’.3’-difluoro-4’-difluoromethylfluorocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluororcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluororcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- 5- fluorocytidine; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethy -5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 5- fluorocytidine; 3’-Deoxy-3’,3’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] fluorocytidine; 3’-Deoxy-3’,3’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] fluorocytidine; -Chloro-3’-deoxy-3’,3’-difluoro-4’-difluoromethylcytidine; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-O-(2-oxidoH-1,3,2- benzodioxaphosphorinyl)-uridine; -Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-O-(2-sulfideH-1,3,2- benzodioxaphosphorinyl)-uridine; -Chloro-3’-deoxy -3’,3’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] cytidine; -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)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyladenosine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyladenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyladenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- adenosine; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylguanosine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- guanosine; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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.

The application provides a compound of Formula I for use as a therapeutically active substance.

The application provides a pharmaceutical composition comprising a compound in accordance with Formula I and a therapeutically inert carrier.

The application provides the above pharmaceutical composition, in combination with one or more antiviral compounds.

The application provides the above pharmaceutical composition, wherein the one or more antiviral compounds comprises one or more anti-Influenza compounds.

The application provides a compound of Formula I for use in the treatment or prophylaxis of Influena infection.

The application provides a pharmaceutical composition comprising a compound in accordance with Formula I for use in the treatment or prophylaxis of Influena infection.

The application provides a composition comprising the compound of Formula I.

The application provides the above composition of Formula I, admixed with at least one carrier, diluent or excipient.

The application provides a composition comprising the compound of Formula I in combination with one or more antiviral compounds.

The application provides a composition comprising the compound of Formula I in combination with one or more anti-Influenza compounds.

The application provides a composition comprising the compound of Formula I in combination with one or more antiviral compounds, admixed with at least one carrier, diluent or excipient.

The application provides a composition comprising the compound of Formula I in combination with one or more anti-Influenza compounds, admixed with at least one carrier, diluent or excipient.

Described is a method of preventing or treating a virus comprising administering to a patient in need thereof a therapeutically effective amount of the compound of Formula I.

Described is 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, or a compound resulting in the formation of a compound of Formula I in vivo, Base wherein: Y is H or P(=X)(R’)(R); 1 1’ R is O-R or NHR ; 1’ 2a 2b 3 R is -C(R )(R )C(=O)OR ; 4 2a 2b 3 3 R’ is N(R )C(R )(R )C(=O)OR , –OP(=O)(OH)OP(=O)(OH)OH, or –OR ; R 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, 1a 1a 1b 1c 1c halo, lower haloalkyl, -N(R ) , acylamino, -SO N(R ) , -C(=O)R , -SO (R ), -NHSO (R ), 2 2 2 2 2 nitro, cyano, or R ; each R is independently H or lower alkyl; 1b 1a 1a each R is independently -OR or -N(R ) ; each R is lower alkyl; 2a 2b 1a each R and R is independently H, lower alkyl, -(CH ) N(R ) , lower 2 r 2 hydroxyalkyl, -CH SH, -(CH )S(O) Me, -(CH ) NHC(=NH)NH , (1H-indolyl)methyl, (1H- 2 2 p 2 n 2 indolyl)methyl, -(CH2) C(=O)R , 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; 2a 2b 4 or R is H and R and R together form (CH ) ; each R is independently H, lower alkyl, lower haloalkyl, phenyl or phenyl lower alkyl, wherein phenyl and phenyl lower alkyl are optionally substituted with lower alkoxy; 3 1’’ or R and R together form CH ; each R is independently H, lower alkyl; 2b 4 or R and R together form (CH ) ; w y z R , R , and R are each independently H, OH or F; R is H, OH, or F; or R and R together form a bond; or R and R 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; and w y z z with the proviso that if R is H, R is H, and R is H, then R is not H; or a pharmacologically acceptable salt thereof. [0077a] Described is 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 or a compound resulting in the formation of a compound of Formula I in vivo, Base wherein: Y is H or P(=X)(R’)(R); 1 1’ R is O-R or NHR ; 1’ 2a 2b 3 R is -C(R )(R )C(=O)OR ; 4 2a 2b 3 3 R’ is N(R )C(R )(R )C(=O)OR , –OP(=O)(OH)OP(=O)(OH)OH, or –OR ; R 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, 1a 1a 1b 1c 1c halo, lower haloalkyl, -N(R ) , acylamino, -SO N(R ) , -C(=O)R , -SO (R ), -NHSO (R ), 2 2 2 2 2 nitro, cyano, or R ; each R is independently H or lower alkyl; 1b 1a 1a each R is independently -OR or -N(R ) ; each R is lower alkyl; 2a 2b 1a each R and R is independently H, lower alkyl, -(CH2)rN(R )2, lower hydroxyalkyl, -CH SH, -(CH )S(O) Me, -(CH ) NHC(=NH)NH , (1H-indolyl)methyl, (1H- 2 2 p 2 n 2 indolyl)methyl, -(CH2) C(=O)R , 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; 2a 2b 4 or R is H and R and R together form (CH ) ; each R is independently H, lower alkyl, lower haloalkyl, phenyl or phenyl lower alkyl, wherein phenyl and phenyl lower alkyl are optionally substituted with lower alkoxy; 3 1’’ or R and R together form CH ; each R is independently H, lower alkyl; 2b 4 or R and R together form (CH ) ; w y z R , R , and R are each independently H, OH or F; R is H, OH, or F; or R and R together form a bond; or R and R together form a bond; X is O or S; and Base is uracil, cytosine, guanine, adenine, or thymine, 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. [0077b] Also described is a corresponding method of treatment wherein in the compound of formula I the base is heterocycloalkyl which may be substituted with one or more hydroxy, lower alkyl, lower alkoxy, halo, nitro or cyano.

Described is 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 or a compound resulting in the formation of a compound of Formula I in vivo.

Described is the use of a compound of Formula I in the preparation of a medicament for the treatment of a viral infection.

The application provides the use of the compound of Formula I in the preparation of a medicament for the treatment of an Influenza infection.

Described is any compound, composition, method, or use as described herein.

Described is the above method, further comprising administering an immune system modulator or one or more antiviral agents that inhibits replication of Influenza, or a combination thereof.

Described is the above method for inhibiting replication of Influenza in a cell comprising administering a compound of Formula I.

Examples of representative compounds encompassed by the present invention and within the scope of the invention are provided in the following Tables. These examples and preparations which follow are provided to enable those skilled in the art to more clearly understand and to practice the present invention. They should not be considered as limiting the scope of the invention, but merely as being illustrative and representative thereof.

In general, the nomenclature used in this Application is based on standard nucleic acid nomenclature common to one of ordinary skill in the art. If there is a discrepancy between a depicted structure and a name given that structure, the depicted structure is to be accorded more weight. In addition, if the stereochemistry of a structure or a portion of a structure is not indicated with, for example, bold or dashed lines, the structure or portion of the structure is to be interpreted as encompassing all stereoisomers of it.

Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number I-1 4’-Difluoromethyluridine 4’-Difluoromethyluridine-5’- (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyluridine-5’- (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyluridine-5’- (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyluridine-5’- (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyluridine-5’- (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyluridine-5’- (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyluridine-5’- {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate} 4’-Difluoromethyluridine-5’- {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate} Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-10 benzodioxaphosphorinyl)- uridine 4’-Difluoromethyl-5’-O-(2- sulfideH-1,3,2- I-11 benzodioxaphosphorinyl)- uridine 4’-Difluoromethyl-5’-O- [bis(4- I-12 methoxyphenoxy)phosphinyl] uridine 4’-Difluoromethyl-5’-O- [bis(4- I-13 methoxyphenoxy)thiophosphin yl] uridine 4’-Difluoromethyluridine- I-14 3’,5’-cyclic phosphoric acid isopropyl ester 4’-Difluoromethyluridine- I-15 3’,5’-cyclic thiophosphoric acid isopropyl ester Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl I-16 fluorouridine 4’-Difluoromethyl fluorouridine-5’-(O-phenyl-N- I-17 (S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl fluorouridine-5’-(O-phenyl-N- I-18 (S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl fluorouridine-5’-(O I-19 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl fluorouridine-5’-(O I-20 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl fluorouridine-5’-(O I-21 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl fluorouridine-5’-(O I-22 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyluridine-5’- {N,N’-bis[(S) I-23 (isopropoxylcarbonyl)ethyl]ph osphorodiamidate} 4’-Difluoromethyl5- fluorouridine-5’-{N,N’- I-24 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate} Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-25 benzodioxaphosphorinyl)- -fluorouridine 4’-Difluoromethyl-5’-O-(2- sulfideH-1,3,2- I-26 benzodioxaphosphorinyl)- -fluorouridine 4’-Difluoromethyl-5’-O- [bis(4- I-27 methoxyphenoxy)phosphinyl] fluorouridine 4’-Difluoromethyl-5’-O- [bis(4- I-28 methoxyphenoxy)thiophosphin yl] fluorouridine 4’-Difluoromethyl I-29 fluorouridine-3’,5’-cyclic phosphoric acid isopropyl ester 4’-Difluoromethyl fluorouridine-3’,5’-cyclic I-30 thiophosphoric acid isopropyl ester Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl I-31 chlorouridine 4’-Difluoromethyl chlorouridine-5’-(O-phenyl-N- I-32 (S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl chlorouridine-5’-(O-phenyl-N- I-33 (S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl chlorouridine-5’-(O I-34 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl chlorouridine-5’-(O I-35 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl chlorouridine-5’-(O I-36 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl chlorouridine-5’-(O I-37 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl chlorouridine-5’-{N,N’- I-38 bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate} 4’-Difluoromethyl chlorouridine-5’-{N,N’- I-39 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate} Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-40 benzodioxaphosphorinyl)- -chlorouridine 4’-Difluoromethyl-5’-O-(2- sulfideH-1,3,2- I-41 benzodioxaphosphorinyl)- -chlorouridine 4’-Difluoromethyl-5’-O- [bis(4- I-42 methoxyphenoxy)phosphinyl]- -chlorouridine 4’-Difluoromethyl-5’-O- [bis(4- I-43 methoxyphenoxy)thiophosphin yl]chlorouridine 4’-Difluoromethyl I-44 chlorouridine-3’,5’-cyclic phosphoric acid isopropyl ester 4’-Difluoromethyl chlorouridine-3’,5’-cyclic I-45 thiophosphoric acid isopropyl ester Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number I-46 4’-Difluoromethylcytidine 4’-Difluoromethylcytidine-5’- (O-phenyl-N-(S) I-47 (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethylcytidine-5’- (O-phenyl-N-(S) I-48 (benzyloxycarbonyl)ethyl phosphoramidate 4’-Difluoromethylcytidine-5’- (O-phenyl-N-(S) I-49 (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethylcytidine-5’- (Onaphthyl-N-(S) I-50 (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethylcytidine-5’- (Onaphthyl-N-(S) I-51 (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethylcytidine-5’- (Onaphthyl-N-(S) I-52 (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethylcytidine-5’- (Onaphthyl-N-(S) I-53 (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethylcytidine-5’- {N,N’-bis[(S) I-54 (isopropoxylcarbonyl)ethyl]ph osphorodiamidate} Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethylcytidine-5’- {N,N’-bis[(S) I-55 (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate} 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-56 benzodioxaphosphorinyl)- cytidine 4’-Difluoromethyl-5’-O-(2- sulfideH-1,3,2- I-57 benzodioxaphosphorinyl)- cytidine 4’-Difluoromethyl-5’-O- [bis(4- I-58 methoxyphenoxy)phosphinyl] cytidine 4’-Difluoromethyl-5’-O- [bis(4- I-59 methoxyphenoxy)thiophosphin yl] cytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethylcytidine- I-60 3’,5’-cyclic phosphoric acid isopropyl ester 4’-Difluoromethylcytidine- I-61 3’,5’-cyclic thiophosphoric acid isopropyl ester 4’-Difluoromethyl I-62 fluorocytidine 4’-Difluoromethyl fluorocytidine-5’-(O-phenyl- I-63 N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl fluorocytidine-5’-(O-phenyl- I-64 N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl fluorocytidine-5’-(O I-65 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl fluorocytidine-5’-(O I-656 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl fluorocytidine-5’-(O I-67 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl fluorocytidine-5’-(O I-68 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl fluorocytidine-5’-{N,N’- I-69 bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate} Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl fluorocytidine-5’-{N,N’- I-70 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate} 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-71 benzodioxaphosphorinyl)- -fluorocytidine 4’-Difluoromethyl-5’-O-(2- sulfideH-1,3,2- I-72 benzodioxaphosphorinyl)- -fluorocytidine 4’-Difluoromethyl-5’-O- [bis(4- I-73 methoxyphenoxy)phosphinyl] fluorocytidine 4’-Difluoromethyl-5’-O- [bis(4- I-74 methoxyphenoxy)thiophosphin yl] fluorocytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl I-75 fluorcytidine-3’,5’-cyclic phosphoric acid isopropyl ester 4’-Difluoromethyl fluorocytidine-3’,5’-cyclic I-76 thiophosphoric acid isopropyl ester 4’-Difluoromethyl I-77 chlorocytidine 4’-Difluoromethyl chlorocytidine-5’-(O-phenyl- I-78 N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl chlorocytidine-5’-(O-phenyl- I-79 N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl5- chlorocytidine-5’-(O I-80 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl chlorocytidine-5’-(O I-81 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl chlorocytidine-5’-(O I-82 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl chlorocytidine-5’-(O I-83 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl chlorocytidine-5’-{N,N’- I-84 bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate} Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl chlorocytidine-5’-{N,N’- I-85 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate} 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-86 benzodioxaphosphorinyl)- -chlorocytidine 4’-Difluoromethyl-5’-O-(2- sulfideH-1,3,2- I-87 benzodioxaphosphorinyl)- -chlorocytidine 4’-Difluoromethyl-5’-O- [bis(4- I-88 methoxyphenoxy)phosphinyl] chlorocytidine 4’-Difluoromethyl-5’-O- [bis(4- I-89 methoxyphenoxy)thiophosphin yl] chlorocytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl I-90 chlorocytidine-3’,5’-cyclic phosphoric acid isopropyl ester 4’-Difluoromethyl chlorocytidine-3’,5’-cyclic I-91 thiophosphoric acid isopropyl ester I-92 4’-Difluoromethyladenosine 4’-Difluoromethyladenosine- ’-(O-phenyl-N-(S) I-93 (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyladenosine- ’-(O-phenyl-N-(S) I-94 (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyladenosine- ’-(Onaphthyl-N-(S) I-95 (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyladenosine- ’-(Onaphthyl-N-(S) I-96 (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyladenosine- ’-(Onaphthyl-N-(S) I-97 (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyladenosine- ’-(Onaphthyl-N-(S) I-98 (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyladenosine- ’-{N,N’-bis[(S) I-99 (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 4’-Difluoromethyladenosine- ’-{N,N’-bis[(S) I-100 (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-101 benzodioxaphosphorinyl)- adenosine 4’-Difluoromethyl-5’-O-(2- sulfideH-1,3,2- I-102 benzodioxaphosphorinyl)- adenosine 4’-Difluoromethyl-5’-O- [bis(4- I-103 methoxyphenoxy)phosphinyl] adenosine 4’-Difluoromethyl-5’-O- [bis(4- I-104 methoxyphenoxy)thiophosphin yl] adenosine 4’-Difluoromethyladenosine- I-105 3’,5’-cyclic phosphoric acid isopropyl ester 4’-Difluoromethyladenosine- I-106 3’,5’-cyclic thiophosphoric acid isopropyl ester Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl I-107 adenosine 4’-Difluoromethyl adenosine-5’-(O-phenyl-N-(S)- I-108 1-(isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl adenosine-5’-(O-phenyl-N-(S)- I-109 1-(isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyladenosine- ’-(Onaphthyl-N-(S) I-110 (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl adenosine-5’-(Onaphthyl- I-111 N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl adenosine-5’-(Onaphthyl- I-112 N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl adenosine-5’-(Onaphthyl- I-113 N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl adenosine-5’-{N,N’-bis[(S) I-114 (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 4’-Difluoromethyl adenosine-5’-{N,N’-bis[(S) I-115 (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-116 benzodioxaphosphorinyl)- 7-adenosine 4’-Difluoromethyl-5’-O-(2- sulfideH-1,3,2- I-117 benzodioxaphosphorinyl)- 7-adenosine 4’-Difluoromethyl-5’-O- [bis(4- I-118 methoxyphenoxy)phosphinyl]- 7-adenosine 4’-Difluoromethyl-5’-O- [bis(4- I-119 methoxyphenoxy)thiophosphin yl] adenosine 4’-Difluoromethyl I-120 adenosine-3’,5’-cyclic phosphoric acid isopropyl ester 4’-Difluoromethyl adenosine-3’,5’-cyclic I-121 thiophosphoric acid isopropyl ester Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number I-122 4’-Difluoromethylguanosine 4’-Difluoromethylguanosine- ’-(O-phenyl-N-(S) I-123 (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethylguanosine- ’-(O-phenyl-N-(S) I-124 (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethylguanosine- ’-(Onaphthyl-N-(S) I-125 (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethylguanosine- ’-(Onaphthyl-N-(S) I-126 (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethylguanosine- ’-(Onaphthyl-N-(S) I-127 (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethylguanosine- ’-(Onaphthyl-N-(S) I-128 (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethylguanosine- ’-{N,N’-bis[(S) I-129 (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 4’-Difluoromethylguanosine- ’-{N,N’-bis[(S) I-130 (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-131 benzodioxaphosphorinyl)- guanosine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl-5’-O-(2- sulfideH-1,3,2- I-132 benzodioxaphosphorinyl)- guanosine 4’-Difluoromethyl-5’-O- [bis(4- I-133 methoxyphenoxy)phosphinyl] guanosine 4’-Difluoromethyl-5’-O- [bis(4- I-134 methoxyphenoxy)thiophosphin yl] guanosine 4’-Difluoromethylguanosine- I-135 3’,5’-cyclic phosphoric acid isopropyl ester 4’-Difluoromethylguanosine- I-136 3’,5’-cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’-fluoro-4’- I-137 difluoromethyluridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyluridine-5’-(O- I-138 phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyluridine-5’-(O- I-139 phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyluridine-5’-(O- I-140 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyluridine-5’-(O- I-141 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyluridine-5’-(O- I-142 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyluridine-5’-(O- I-143 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyluridine-5’- I-144 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethyluridine-5’- {N,N’-bis[(S) I-145 (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-146 4-H-1,3,2- benzodioxaphosphorinyl)- uridine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2- I-147 sulfideH-1,3,2- benzodioxaphosphorinyl)- uridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-148 methoxyphenoxy)phosphinyl] uridine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-149 methoxyphenoxy)thiophosphin yl] uridine 2’-Deoxy-2’-fluoro-4’- difluoromethyluridine-3’,5’- I-150 cyclic phosphoric acid isopropyl ester 2’-Deoxy-2’-fluoro-4’- difluoromethyluridine-3’,5’- I-151 cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’-fluoro-4’- I-152 difluoromethylfluorouridine 2’-Deoxy-2’-fluoro-4’- difluoromethyl fluorouridine-5’-(O-phenyl-N- I-153 (S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl fluorouridine-5’-(O-phenyl-N- I-154 (S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl fluorouridine-5’-(O I-155 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyluridine-5’-(O- I-156 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl fluorouridine-5’-(O I-157 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl fluorouridine-5’-(O I-158 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl fluorouridine-5’-{N,N’- I-159 bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl fluorouridine-5’-{N,N’- I-160 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-161 4-H-1,3,2- benzodioxaphosphorinyl)- -fluorouridine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2- I-162 sulfideH-1,3,2- benzodioxaphosphorinyl)- -fluorouridine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-163 methoxyphenoxy)phosphinyl]- -fluorouridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-164 methoxyphenoxy)thiophosphin yl]uridine 2’-Deoxy-2’-fluoro-4’- difluoromethyl I-165 fluorouridine-3’,5’-cyclic phosphoric acid isopropyl ester 2’-Deoxy-2’-fluoro-4’- difluoromethyl I-166 fluorouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’-fluoro-4’- I-167 difluoromethyl chlorouridine 2’-Deoxy-2’-fluoro-4’- difluoromethyl chlorouridine-5’-(O-phenyl-N- I-168 (S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl chlorouridine-5’-(O-phenyl-N- I-169 (S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl chlorouridine-5’-(O I-170 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl chlorouridine-5’-(O I-171 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl chlorouridine-5’-(O I-172 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl chlorouridine-5’-(O I-173 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl chlorouridine-5’-{N,N’- I-174 bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl chlorouridine-5’-{N,N’- I-175 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-176 4-H-1,3,2- benzodioxaphosphorinyl)- -chlorouridine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2- I-177 sulfideH-1,3,2- benzodioxaphosphorinyl)- -chlorouridine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-178 methoxyphenoxy)phosphinyl]- -chlorouridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-179 methoxyphenoxy)thiophosphin yl]chlorouridine 2’-Deoxy-2’-fluoro-4’- difluoromethyl I-180 chlorouridine-3’,5’-cyclic phosphoric acid isopropyl ester 2’-Deoxy-2’-fluoro-4’- difluoromethyl I-181 chlorouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’-fluoro-4’- I-182 difluoromethylcytidine 2’-Deoxy-2’-fluoro-4’- difluoromethylcytidine-5’-(O- I-183 phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylcytidine-5’-(O- I-184 phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethylcytidine-5’-(O- I-185 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylcytidine-5’-(O- I-186 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylcytidine-5’-(O- I-187 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylcytidine-5’-(O- I-188 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylcytidine-5’- I-189 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethylcytidine-5’- I-190 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-191 4-H-1,3,2- benzodioxaphosphorinyl)- cytidine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2- I-192 sulfideH-1,3,2- benzodioxaphosphorinyl)- cytidine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-193 methoxyphenoxy)phosphinyl] cytidine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-194 methoxyphenoxy)thiophosphin yl] cytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-4’-difluoromethyl- I-195 2’-fluorocytidine-3’,5’-cyclic phosphoric acid isopropyl ester 2’-Deoxy-4’-difluoromethyl- 2’-fluorocytidine-3’,5’-cyclic I-196 thiophosphoric acid isopropyl ester 2’-Deoxy-2’-fluoro-4’- I-197 difluoromethyl fluorocytidine 2’-Deoxy-2’-fluoro-4’- difluoromethyl fluorocytidine-5’-(O-phenyl- I-198 N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl fluorocytidine-5’-(O-phenyl- I-199 N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl fluorocytidine-5’-(O I-200 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethylcytidine-5’-(O- I-201 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl fluorocytidine-5’-(O I-202 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl fluorocytidine-5’-(O I-203 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl fluorocytidine-5’-{N,N’- I-204 bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl fluorocytidine-5’-{N,N’- I-205 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-206 4-H-1,3,2- benzodioxaphosphorinyl)- -fluorocytidine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2- I-207 sulfideH-1,3,2- benzodioxaphosphorinyl)- -fluorocytidine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-208 methoxyphenoxy)phosphinyl]- -fluorocytidine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-209 methoxyphenoxy)thiophosphin yl]cytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl I-210 fluorocytidine-3’,5’-cyclic phosphoric acid isopropyl ester 2’-Deoxy-2’-fluoro-4’- difluoromethyl I-211 fluorocytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’-fluoro-4’- I-212 difluoromethyl chlorocytidine 2’-Deoxy-2’-fluoro-4’- difluoromethyl chlorocytidine-5’-(O-phenyl- I-213 N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl chlorocytidine-5’-(O-phenyl- I-214 N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl chlorocytidine-5’-(O I-215 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl chlorocytidine-5’-(O I-216 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl chlorocytidine-5’-(O I-217 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl chlorocytidine-5’-(O I-218 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl chlorocytidine-5’-{N,N’- I-219 bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl chlorocytidine-5’-{N,N’- I-220 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-221 4-H-1,3,2- benzodioxaphosphorinyl)- -chlorocytidine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2- I-222 sulfideH-1,3,2- benzodioxaphosphorinyl)- -chlorocytidine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-223 methoxyphenoxy)phosphinyl]- -chlorocytidine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-224 methoxyphenoxy)thiophosphin yl]chlorocytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl I-225 chlorocytidine-3’,5’-cyclic phosphoric acid isopropyl ester 2’-Deoxy-2’-fluoro-4’- difluoromethyl I-226 chlorocytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’-fluoro-4’- I-227 difluoromethyladenosine 2’-Deoxy-2’-fluoro-4’- difluoromethyladenosine-5’- I-228 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyladenosine-5’- I-229 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyladenosine-5’- I-230 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyladenosine-5’- I-231 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyladenosine-5’- I-232 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyladenosine-5’- I-233 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyladenosine-5’- I-234 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethyladenosine-5’- I-235 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-236 4-H-1,3,2- benzodioxaphosphorinyl)- adenosine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2- I-237 sulfideH-1,3,2- benzodioxaphosphorinyl)- adenosine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-238 methoxyphenoxy)phosphinyl] adenosine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-239 methoxyphenoxy)thiophosphin yl] adenosine 2’-Deoxy-4’-difluoromethyl- 2’-fluoroadenosine-3’,5’- I-240 cyclic phosphoric acid isopropyl ester 2’-Deoxy-4’-difluoromethyl- 2’-fluoroadenosine-3’,5’- I-241 cyclic thiophosphoric acid isopropyl ester Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- I-242 difluoromethyladenosine 2’-Deoxy-2’-fluoro-4’- difluoromethylguanosine-5’- I-243 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyguanosine-5’- I-244 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylguanosine-5’- I-245 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylguanosine-5’- I-246 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethylguanosine-5’- I-247 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylguanosine-5’- I-248 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylguanosine-5’- {N,N’-bis[(S) I-249 (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethylguanosine-5’- I-250 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-251 4-H-1,3,2- benzodioxaphosphorinyl)- guanosine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2- I-252 sulfideH-1,3,2- benzodioxaphosphorinyl)- guanosine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-253 methoxyphenoxy)phosphinyl] guanosine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-254 methoxyphenoxy)thiophosphin yl] guanosine 2’-Deoxy-4’-difluoromethyl- 2’-fluoroguanosine-3’,5’- I-255 cyclic phosphoric acid isopropyl ester 2’-Deoxy-4’-difluoromethyl- 2’-fluoroguanosine-3’,5’- I-256 cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’-fluoro-4’- I-257 difluoromethylarauridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethylarauridine-5’- I-258 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethyarauridine-5’- I-259 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylarauridine-5’- I-260 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylarauridine-5’- I-261 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylarauridine-5’- I-262 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethylarauridine-5’- I-263 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylarauridine-5’- {N,N’-bis[(S) I-264 (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethylarauridine-5’- I-265 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-266 4-H-1,3,2- benzodioxaphosphorinyl)- arauridine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2- I-267 sulfideH-1,3,2- benzodioxaphosphorinyl)- arauridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-268 methoxyphenoxy)phosphinyl] arauridine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-269 methoxyphenoxy)thiophosphin yl] arauridine 2’-Deoxy-4’-difluoromethyl- 2’-fluoroarauridine-3’,5’- I-270 cyclic phosphoric acid isopropyl ester 2’-Deoxy-4’-difluoromethyl- 2’-fluoroarauridine-3’,5’- I-271 cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’,5-difluoro-4’- I-272 difluoromethylarauridine 2’-Deoxy-2’,5-difluoro-4’- difluoromethylarauridine-5’- I-273 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,5-difluoro-4’- difluoromethylarauridine-5’- I-274 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,5-difluoro-4’- difluoromethylarauridine-5’- I-275 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,5-difluoro-4’- difluoromethylarauridine-5’- I-276 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,5-difluoro-4’- difluoromethylarauridine-5’- I-277 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,5-difluoro-4’- difluoromethylarauridine-5’- I-278 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,5-difluoro-4’- difluoromethylarauridine-5’- {N,N’-bis[(S) I-279 (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 2’-Deoxy-2’,5-difluoro-4’- difluoromethylarauridine-5’- I-280 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’,5-difluoro-4’- difluoromethyl-5’-O-(2-oxido- I-281 4-H-1,3,2- benzodioxaphosphorinyl)- arauridine 2’-Deoxy-2’,5-difluoro-4’- difluoromethyl-5’-O-(2- I-282 sulfideH-1,3,2- benzodioxaphosphorinyl)- arauridine 2’-Deoxy-2’,5-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-283 methoxyphenoxy)phosphinyl]- arauridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,5-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-284 methoxyphenoxy)thiophosphin yl]-arauridine 2’-Deoxy-4’-difluoromethyl- 2’,5-difluoroarauridine-3’,5’- I-285 cyclic phosphoric acid isopropyl ester 2’-Deoxy-4’-difluoromethyl- 2’,5-difluoroarauridine-3’,5’- I-286 cyclic thiophosphoric acid isopropyl ester 4-Chloro-2’-deoxy-2’fluoro- I-287 4’-difluoromethylarauridine 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylarauridine- I-28 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylarauridine- I-289 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylarauridine- I-290 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylarauridine- I-291 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylarauridine- I-292 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylarauridine- I-293 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylarauridine- I-294 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylarauridine- I-295 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethyl-5’-O-(2- I-296 oxidoH-1,3,2- benzodioxaphosphorinyl)- arauridine 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethyl-5’-O-(2- I-297 sulfideH-1,3,2- benzodioxaphosphorinyl)- arauridine 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethyl-5’-O-[bis(4- I-298 methoxyphenoxy)phosphinyl]- arauridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethyl-5’-O-[bis(4- I-299 methoxyphenoxy)thiophosphin yl]-arauridine 4-Chloro-2’-deoxy-4’- difluoromethyl-2’- I-300 fluoroarauridine-3’,5’-cyclic phosphoric acid isopropyl ester 4-Chloro-2’-deoxy-4’- difluoromethyl-2’- I-301 fluoroarauridine-3’,5’-cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’-fluoro-4’- I-302 difluoromethylaracytidine 2’-Deoxy-2’-fluoro-4’- difluoromethylaracytidine-5’- I-303 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethlaracytidine-5’- I-304 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethylaracytidine-5’- I-305 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylaracytidine-5’- I-306 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylaracytidine-5’- I-307 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylaracytidine-5’- I-308 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylaracytidine-5’- I-309 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethylaracytidine-5’- I-310 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-311 4-H-1,3,2- benzodioxaphosphorinyl)- aracytidine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2- I-312 sulfideH-1,3,2- benzodioxaphosphorinyl)- aracytidine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-313 methoxyphenoxy)phosphinyl] aracytidine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-314 methoxyphenoxy)thiophosphin yl] aracytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-4’-difluoromethyl- 2’-fluoroaracytidine-3’,5’- I-315 cyclic phosphoric acid isopropyl ester 2’-Deoxy-4’-difluoromethyl- 2’-fluoroaracytidine-3’,5’- I-316 cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’,5-difluoro-4’- I-317 difluoromethylaracytidine 2’-Deoxy-2’,5-difluoro-4’- difluoromethylaracytidine-5’- I-318 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,5-difluoro-4’- difluoromethylaracytidine-5’- I-319 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,5-difluoro-4’- difluoromethylaracytidine-5’- I-320 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,5-difluoro-4’- difluoromethylaracytidine-5’- I-321 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,5-difluoro-4’- difluoromethylaracytidine-5’- I-322 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,5-difluoro-4’- difluoromethylaracytidine-5’- I-323 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,5-difluoro-4’- difluoromethylaracytidine-5’- I-324 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,5-difluoro-4’- difluoromethylaracytidine-5’- I-325 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’,5-difluoro-4’- difluoromethyl-5’-O-(2-oxido- I-326 4-H-1,3,2- benzodioxaphosphorinyl)- aracytidine 2’-Deoxy-2’,5-difluoro-4’- difluoromethyl-5’-O-(2- I-327 sulfideH-1,3,2- benzodioxaphosphorinyl)- aracytidine 2’-Deoxy-2’,5-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-328 methoxyphenoxy)phosphinyl]- aracytidine 2’-Deoxy-2’,5-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-329 methoxyphenoxy)thiophosphin yl]-aracytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-4’-difluoromethyl- 2’,5-difluoroaracytidine-3’,5’- I-330 cyclic phosphoric acid isopropyl ester 2’-Deoxy-4’-difluoromethyl- 2’,5-difluoroaracytidine-3’,5’- I-331 cyclic thiophosphoric acid isopropyl ester 4-Chloro-2’-deoxy-2’fluoro- I-332 4’-difluoromethylaracytidine 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylaracytidine- I-333 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylaracytidine- I-334 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylaracytidine- I-335 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylaracytidine- I-336 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylaracytidine- I-337 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylaracytidine- I-338 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylaracytidine- I-339 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylaracytidine- I-340 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethyl-5’-O-(2- I-341 oxidoH-1,3,2- benzodioxaphosphorinyl)- aracytidine 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethyl-5’-O-(2- I-342 sulfideH-1,3,2- benzodioxaphosphorinyl)- aracytidine 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethyl-5’-O-[bis(4- I-343 methoxyphenoxy)phosphinyl]- aracytidine 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethyl-5’-O-[bis(4- I-344 methoxyphenoxy)thiophosphin yl]-aracytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4-Chloro-2’-deoxy-4’- difluoromethyl-2’- I-345 fluoroaracytidine-3’,5’-cyclic phosphoric acid isopropyl ester 4-Chloro-2’-deoxy-4’- difluoromethyl-2’- I-346 fluoroaracytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’-fluoro-4’- I-347 difluoromethylaraadenosine 2’-Deoxy-2’-fluoro-4’- difluoromethylaraadenosine- I-348 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethlaraadenosine-5’- I-349 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylaraadenosine- I-350 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethylaraadenosine- I-351 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylaraadenosine- I-352 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylaraadenosine- I-353 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylaraadenosine- I-354 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethylaraadenosine- I-355 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-356 4-H-1,3,2- benzodioxaphosphorinyl)- araadenosine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2- I-357 sulfideH-1,3,2- benzodioxaphosphorinyl)- araadenosine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-358 methoxyphenoxy)phosphinyl] araadenosine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-359 methoxyphenoxy)thiophosphin yl] araadenosine 2’-Deoxy-4’-difluoromethyl- 2’-fluoroaraadenosine-3’,5’- I-360 cyclic phosphoric acid isopropyl ester 2’-Deoxy-4’-difluoromethyl- 2’-fluoroaraadenosine-3’,5’- I-361 cyclic thiophosphoric acid isopropyl ester Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- I-362 difluoromethylaraguanosine 2’-Deoxy-2’-fluoro-4’- difluoromethylaraguanosine- I-363 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethlaraguanosine-5’- I-364 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylaraguanosine- I-365 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylaraguanosine- I-366 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethylaraguanosine- I-367 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylaraguanosine- I-368 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’- difluoromethylaraguanosine- I-369 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethylaraguanosine- I-370 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-371 4-H-1,3,2- benzodioxaphosphorinyl)- araguanosine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-(2- I-372 sulfideH-1,3,2- benzodioxaphosphorinyl)- araguanosine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-373 methoxyphenoxy)phosphinyl] araguanosine 2’-Deoxy-2’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-374 methoxyphenoxy)thiophosphin yl] araguanosine 2’-Deoxy-4’-difluoromethyl- 2’-fluoroaraguanosine-3’,5’- I-375 cyclic phosphoric acid isopropyl ester 2’-Deoxy-4’-difluoromethyl- 2’-fluoroaraguanosine-3’,5’- I-376 cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’,2’-difluoro-4’- I-377 difluoromethyluridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyluridine-5’-(O- I-378 phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyluridine-5’-(O- I-379 phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyluridine-5’-(O- I-380 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyluridine-5’-(O- I-381 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyluridine-5’-(O- I-382 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyluridine-5’-(O- I-383 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyluridine-5’- I-384 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyluridine-5’- I-385 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-(2-oxido- I-386 4-H-1,3,2- benzodioxaphosphorinyl)- uridine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-(2- I-387 sulfideH-1,3,2- benzodioxaphosphorinyl)- uridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-388 methoxyphenoxy)phosphinyl] uridine 2’-Deoxy-2’,2’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-389 methoxyphenoxy)thiophosphin yl] uridine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyluridine-3’,5’- I-390 cyclic phosphoric acid isopropyl ester 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyluridine-3’,5’- I-391 cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’,2’-difluoro-4’- I-392 difluoromethylfluorouridine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl fluorouridine-5’-(O-phenyl-N- I-393 (S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl fluorouridine-5’-(O-phenyl-N- I-394 (S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl fluorouridine-5’-(O I-395 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl fluorouridine-5’-(O I-396 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl fluorouridine-5’-(O I-397 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl fluorouridine-5’-(O I-398 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl fluorouridine-5’-{N,N’- I-399 bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl fluorouridine-5’-{N,N’- I-400 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-(2-oxido- I-401 4-H-1,3,2- benzodioxaphosphorinyl)- -fluorouridine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-(2- I-402 sulfideH-1,3,2- benzodioxaphosphorinyl)- -fluorouridine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-403 methoxyphenoxy)phosphinyl]- -fluorouridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-404 methoxyphenoxy)thiophosphin yl]uridine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl I-405 fluorouridine-3’,5’-cyclic phosphoric acid isopropyl ester 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl I-406 fluorouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’,2’-difluoro-4’- I-407 difluoromethyl chlorouridine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl chlorouridine-5’-(O-phenyl-N- I-408 (S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl chlorouridine-5’-(O-phenyl-N- I-409 (S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl chlorouridine-5’-(O I-410 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl chlorouridine-5’-(O I-411 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl chlorouridine-5’-(O I-412 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl chlorouridine-5’-(O I-413 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl chlorouridine-5’-{N,N’- I-414 bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl chlorouridine-5’-{N,N’- I-415 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-(2-oxido- I-416 4-H-1,3,2- benzodioxaphosphorinyl)- -chlorouridine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-(2- I-417 sulfideH-1,3,2- benzodioxaphosphorinyl)- -chlorouridine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-418 methoxyphenoxy)phosphinyl]- -chlorouridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-419 methoxyphenoxy)thiophosphin yl]chlorouridine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl I-420 chlorouridine-3’,5’-cyclic phosphoric acid isopropyl ester 2’-Deoxy-2’,2’-fluoro-4’- difluoromethyl I-421 chlorouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’,2’-difluoro-4’- I-422 difluoromethylcytidine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylcytidine-5’-(O- I-423 phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylcytidine-5’-(O- I-424 phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylcytidine-5’-(O- I-425 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylcytidine-5’-(O- I-426 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylcytidine-5’-(O- I-427 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylcytidine-5’-(O- I-428 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylcytidine-5’- I-429 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylcytidine-5’- I-430 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-(2-oxido- I-431 4-H-1,3,2- benzodioxaphosphorinyl)- cytidine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-(2- I-432 sulfideH-1,3,2- benzodioxaphosphorinyl)- cytidine 2’-Deoxy-2’,2’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-433 methoxyphenoxy)phosphinyl] cytidine 2’-Deoxy-2’,2’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-434 methoxyphenoxy)thiophosphin yl] cytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylcytdine-3’,5’- I-435 cyclic phosphoric acid isopropyl ester 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylcytidine-3’,5’- I-436 cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’,2’-difluoro-4’- I-437 difluoromethyl fluorocytidine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl fluorocytidine-5’-(O-phenyl- I-438 N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl fluorocytidine-5’-(O-phenyl- I-439 N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl fluorocytidine-5’-(O I-440 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl fluorocytidine-5’-(O I-441 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl fluorocytidine-5’-(O I-442 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl fluorocytidine-5’-(O I-443 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl fluorocytidine-5’-{N,N’- I-444 bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl fluorocytidine-5’-{N,N’- I-445 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-(2-oxido- I-446 4-H-1,3,2- benzodioxaphosphorinyl)- -fluoroucytidine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-(2- I-447 sulfideH-1,3,2- benzodioxaphosphorinyl)- -fluorocytidine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-448 methoxyphenoxy)phosphinyl]- -fluorocytidine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-449 methoxyphenoxy)thiophosphin yl]cytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl I-450 fluorocytidine-3’,5’-cyclic phosphoric acid isopropyl ester 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl I-451 fluorocytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester -Chloro-2’-deoxy-2’,2’- I-452 difluoro-4’- difluoromethylcytidine -Chloro-2’-deoxy-2’,2’- difluoro-4’- difluoromethylcytidine-5’-(O- I-453 phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-2’-deoxy-2’,2’- difluoro-4’- difluoromethylcytidine-5’-(O- I-454 phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-2’-deoxy-2’,2’- difluoro-4’- difluoromethylcytidine-5’-(O- I-455 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-2’-deoxy-2’,2’- difluoro-4’- difluoromethylcytidine-5’-(O- I-456 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-2’-deoxy-2’,2’- difluoro-4’- difluoromethylcytidine-5’-(O- I-457 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-2’-deoxy-2’,2’- difluoro-4’- difluoromethylcytidine-5’-(O- I-458 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-2’-deoxy-2’,2’- difluoro-4’- difluoromethylcytidine-5’- I-459 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-2’-deoxy-2’,2’- difluoro-4’- difluoromethylcytidine-5’- I-460 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate -Chloro-2’-deoxy-2’,2’- difluoro-4’-difluoromethyl-5’- I-461 O-(2-oxidoH-1,3,2- benzodioxaphosphorinyl) cytidine -Chloro-2’-deoxy-2’,2’- difluoro-4’-difluoromethyl-5’- I-462 O-(2-sulfideH-1,3,2- benzodioxaphosphorinyl) cytidine -Chloro-2’-deoxy-2’,2’- difluoro-4’-difluoromethyl-5’- I-463 O-[bis(4- methoxyphenoxy)phosphinyl] cytidine -Chloro-2’-deoxy-2’,2’- difluoro-4’-difluoromethyl-5’- I-464 O-[bis(4- methoxyphenoxy)thiophosphin yl] cytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-2’-deoxy-2’,2’- difluoro-4’- I-465 difluoromethylcytidine-3’,5’- cyclic phosphoric acid isopropyl ester -Chloro-2’-deoxy-2’,2’- difluoro-4’- I-466 difluoromethylcytidine-3’,5’- cyclic thiophosphoric acid isopropyl ester 2’-Deoxy-2’,2’-difluoro-4’- I-467 difluoromethyladenosine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyladenosine-5’- I-468 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyladenosine-5’- I-469 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyladenosine-5’- I-470 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyladenosine-5’- I-471 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyladenosine-5’- I-472 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyladenosine-5’- I-473 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyladenosine-5’- I-474 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyladenosine-5’- I-475 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-(2-oxido- I-476 4-H-1,3,2- benzodioxaphosphorinyl)- adenosine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyl-5’-O-(2- I-477 sulfideH-1,3,2- benzodioxaphosphorinyl)- adenosine 2’-Deoxy-2’,2’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-478 methoxyphenoxy)phosphinyl] adenosine 2’-Deoxy-2’,2’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-479 methoxyphenoxy)thiophosphin yl] adenosine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyladenosine- I-480 3’,5’-cyclic phosphoric acid isopropyl ester 2’-Deoxy-2’,2’-difluoro-4’- difluoromethyladenosine- I-481 3’,5’-cyclic thiophosphoric acid isopropyl ester Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- I-482 difluoromethylguanosine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylguanosine-5’- I-483 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylguanosine-5’- I-484 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylguanosine-5’- I-485 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylguanosine-5’- I-486 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylguanosine-5’- I-487 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylguanosine-5’- I-488 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylguanosine-5’- I-489 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylguanosine-5’- I-490 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylguanosine-5’- I-491 O-(2-oxidoH-1,3,2- benzodioxaphosphorinyl)- cytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylguanosine-5’- I-492 O-(2-sulfideH-1,3,2- benzodioxaphosphorinyl)- cytidine 2’-Deoxy-2’,2’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-493 methoxyphenoxy)phosphinyl] guanosine 2’-Deoxy-2’,2’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-494 methoxyphenoxy)thiophosphin yl] guanosine 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylguanosine- I-495 3’,5’-cyclic phosphoric acid isopropyl ester 2’-Deoxy-2’,2’-difluoro-4’- difluoromethylguanosine- I-496 3’,5’-cyclic thiophosphoric acid isopropyl ester I-497 4’-Difluoromethylarauridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethylarauridine- ’-(O-phenyl-N-(S) I-498 (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethlarauridine- ’-(O-phenyl-N-(S) I-499 (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethylarauridine- ’-(Onaphthyl-N-(S) I-500 (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethylarauridine- ’-(Onaphthyl-N-(S) I-501 (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethylarauridine- ’-(Onaphthyl-N-(S) I-502 (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethylarauridine- ’-(Onaphthyl-N-(S) I-503 (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethylarauridine- ’-{N,N’-bis[(S) I-504 (isopropoxylcarbonyl)ethyl]ph osphorodiamidate} 4’-Difluoromethylarauridine- ’-{N,N’-bis[(S) I-505 (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate} 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-506 benzodioxaphosphorinyl)- arauridine 4’-Difluoromethyl-5’-O-(2- sulfideH-1,3,2- I-507 benzodioxaphosphorinyl)- arauridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl-5’-O- [bis(4- I-508 methoxyphenoxy)phosphinyl] arauridine 4’-Difluoromethyl-5’-O- [bis(4- I-509 methoxyphenoxy)thiophosphin yl] arauridine 4’-Difluoromethylarauridine- I-510 3’,5’-cyclic phosphoric acid isopropyl ester 4’-Difluoromethylarauridine- I-511 3’,5’-cyclic thiophosphoric acid isopropyl ester 4’-Difluoromethyl I-512 fluoroarauridine 4’-Difluoromethyl fluoroarauridine-5’-(O-phenyl- I-513 N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl fluoroarauridine-5’-(O-phenyl- I-514 N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl fluoroarauridine-5’-(O I-515 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl fluoroarauridine-5’-(O I-516 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl fluoroarauridine-5’-(O I-517 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl fluoroarauridine-5’-(O I-518 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-difluoromethyl fluoroarauridine-5’-{N,N’- I-519 bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 4’-Difluoromethyl fluoroarauridine-5’-{N,N’- I-520 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-521 benzodioxaphosphorinyl)- -fluoroarauridine 2’-Deoxy-2’,5-difluoro-4’- difluoromethyl-5’-O-(2- I-522 sulfideH-1,3,2- benzodioxaphosphorinyl)- -fluoroarauridine 2’-Deoxy-2’,5-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-523 methoxyphenoxy)phosphinyl]- -fluoroarauridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 2’-Deoxy-2’,5-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-524 methoxyphenoxy)thiophosphin yl]fluoroarauridine 4’-Difluoromethyl I-525 fluoroarauridine-3’,5’-cyclic phosphoric acid isopropyl ester 4’-Difluoromethyl fluoroarauridine-3’,5’-cyclic I-526 thiophosphoric acid isopropyl ester -Chloro-4’- I-527 difluoromethylarauridine -Chloro-4’- difluoromethylarauridine-5’- I-528 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-4’- difluoromethylarauridine-5’- I-529 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-4’- difluoromethylarauridine-5’- I-530 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylarauridine- I-531 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-4’- difluoromethylarauridine-5’- I-532 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-4’- difluoromethylarauridine-5’- I-533 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-4’- difluoromethylarauridine-5’- {N,N’-bis[(S) I-534 (isopropoxylcarbonyl)ethyl]ph osphorodiamidate -Chloro -4’- difluoromethylarauridine-5’- {N,N’-bis[(S) I-535 (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate -Chloro-4’-difluoromethyl- ’-O-(2-oxidoH-1,3,2- I-536 benzodioxaphosphorinyl)- arauridine -Chloro-4’-difluoromethyl- ’-O-(2-sulfideH-1,3,2- I-537 benzodioxaphosphorinyl)- arauridine -Chloro-4’-difluoromethyl- ’-O-[bis(4- I-538 methoxyphenoxy)phosphinyl]- arauridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-4’-difluoromethyl- ’-O-[bis(4- I-539 methoxyphenoxy)thiophosphin yl]-arauridine -Chloro-4’- difluoromethylarauridine- I-540 3’,5’-cyclic phosphoric acid isopropyl ester -Chloro-4’- difluoromethylarauridine- I-541 3’,5’-cyclic thiophosphoric acid isopropyl ester I-542 4’-Difluoromethylaracytidine 4’-Difluoromethylaracytidine- ’-(O-phenyl-N-(S) I-543 (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethlaracytidine- ’-(O-phenyl-N-(S) I-544 (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethylaracytidine- ’-(Onaphthyl-N-(S) I-545 (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethylaracytidine- ’-(Onaphthyl-N-(S) I-546 (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethylaracytidine- ’-(Onaphthyl-N-(S) I-547 (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethylaracytidine- ’-(Onaphthyl-N-(S) I-548 (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethylaracytidine- ’-{N,N’-bis[(S) I-549 (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethylaracytidine- ’-{N,N’-bis[(S) I-550 (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-551 benzodioxaphosphorinyl)- aracytidine 4’-Difluoromethyl-5’-O-(2- sulfideH-1,3,2- I-552 benzodioxaphosphorinyl)- aracytidine 4’-Difluoromethyl-5’-O- [bis(4- I-553 methoxyphenoxy)phosphinyl] aracytidine 4’-Difluoromethyl-5’-O- [bis(4- I-554 methoxyphenoxy)thiophosphin yl] aracytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethylaracytidine- I-555 3’,5’-cyclic phosphoric acid isopropyl ester 4’-Difluoromethylaracytidine- I-556 3’,5’-cyclic thiophosphoric acid isopropyl ester 4’-Difluoromethyl I-557 fluoroaracytidine 4’-Difluoromethyl fluoroaracytidine-5’-(O- I-558 phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl fluoroaracytidine-5’-(O- I-559 phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl fluoroaracytidine-5’-(O I-560 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl fluoroaracytidine-5’-(O I-561 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl fluoroaracytidine-5’-(O I-562 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl fluoroaracytidine-5’-(O I-563 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-difluoromethyl fluoroaracytidine-5’-{N,N’- I-564 bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl fluoroaracytidine-5’-{N,N’- I-565 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-566 benzodioxaphosphorinyl)- -fluoroaracytidine 2’-Deoxy-2’,5-difluoro-4’- difluoromethyl-5’-O-(2- I-567 sulfideH-1,3,2- benzodioxaphosphorinyl)- -fluoroaracytidine 2’-Deoxy-2’,5-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-568 methoxyphenoxy)phosphinyl]- -fluoroaracytidine 2’-Deoxy-2’,5-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-569 methoxyphenoxy)thiophosphin yl]fluoroaracytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl—5- I-570 fluoroaracytidine-3’,5’-cyclic phosphoric acid isopropyl ester 4’-Difluoromethyl fluoroaracytidine-3’,5’-cyclic I-571 thiophosphoric acid isopropyl ester -Chloro-4’- I-572 difluoromethylaracytidine -Chloro-4’- difluoromethylaracytidine-5’- I-574 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-4’- difluoromethylaracytidine-5’- I-575 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-4’- difluoromethylaracytidine-5’- I-576 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4-Chloro-2’-deoxy-2’-fluoro- 4’-difluoromethylaracytidine- I-577 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-4’- difluoromethylaracytidine-5’- I-578 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-4’- difluoromethylaracytidine-5’- I-579 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-4’- difluoromethylaracytidine-5’- I-580 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro -4’- difluoromethylaracytidine-5’- I-581 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate -Chloro-4’-difluoromethyl- ’-O-(2-oxidoH-1,3,2- I-582 benzodioxaphosphorinyl)- aracytidine -Chloro-4’-difluoromethyl- ’-O-(2-sulfideH-1,3,2- I-583 benzodioxaphosphorinyl)- aracytidine -Chloro-4’-difluoromethyl- ’-O-[bis(4- I-584 methoxyphenoxy)phosphinyl]- aracytidine -Chloro-4’-difluoromethyl- ’-O-[bis(4- I-585 methoxyphenoxy)thiophosphin yl]-aracytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-4’- difluoromethylaracytidine- I-586 3’,5’-cyclic phosphoric acid isopropyl ester -Chloro-4’- difluoromethylaracytidine- I-587 3’,5’-cyclic thiophosphoric acid isopropyl ester I-588 Difluoromethylaraadenosine Difluoromethylaraadenosine- I-589 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Difluoromethlaraadenosine-5’- I-590 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Difluoromethylaraadenosine- I-591 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number Difluoromethylaraadenosine- I-592 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Difluoromethylaraadenosine- I-593 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Difluoromethylaraadenosine- I-594 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Difluoromethylaraadenosine- I-595 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Difluoromethylaraadenosine- I-596 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-597 benzodioxaphosphorinyl)- araadenosine 4’-Difluoromethyl-5’-O-(2- sulfideH-1,3,2- I-598 benzodioxaphosphorinyl)- araadenosine 4’-Difluoromethyl-5’-O- [bis(4- I-599 methoxyphenoxy)phosphinyl] araadenosine 4’-Difluoromethyl-5’-O- [bis(4- I-600 methoxyphenoxy)thiophosphin yl] araadensoine Difluoromethylaraadenosine- I-601 3’,5’-cyclic phosphoric acid isopropyl ester Difluoromethylaraadenosine- I-602 3’,5’-cyclic thiophosphoric acid isopropyl ester Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number I-603 Difluoromethylaraguanosine Difluoromethylaraguanosine- I-604 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Difluoromethlaraadenosine-5’- I-605 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Difluoromethylaraguanosine- I-606 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Difluoromethylaraguanosine- I-607 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number Difluoromethylaraguanosine- I-608 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Difluoromethylaraguanosine- I-609 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Difluoromethylaraguanosine- I-610 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Difluoromethylaraguanosine- I-611 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-612 benzodioxaphosphorinyl)- araguanosine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl-5’-O-(2- sulfideH-1,3,2- I-613 benzodioxaphosphorinyl)- araguanosine 4’-Difluoromethyl-5’-O- [bis(4- I-614 methoxyphenoxy)phosphinyl] araguanosine 4’-Difluoromethyl-5’-O- [bis(4- I-615 methoxyphenoxy)thiophosphin yl] araguanosine Difluoromethylaraguanosine- I-616 3’,5’-cyclic phosphoric acid isopropyl ester Difluoromethylaraguanosine- I-617 3’,5’-cyclic thiophosphoric acid isopropyl ester 3’-Deoxy-3’-fluoro-4’- I-618 difluoromethyluridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’-fluoro-4’- difluoromethyluridine-5’-(O- I-619 phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethyluridine-5’-(O- I-620 phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethyluridine-5’-(O- I-621 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethyluridine-5’-(O- I-622 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethyluridine-5’-(O- I-623 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’-fluoro-4’- difluoromethyluridine-5’-(O- I-624 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethyluridine-5’- I-625 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 3’-Deoxy-3’-fluoro-4’- difluoromethyluridine-5’- I-626 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-627 4-H-1,3,2- benzodioxaphosphorinyl)- uridine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-(2- I-628 sulfideH-1,3,2- benzodioxaphosphorinyl)- uridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-629 methoxyphenoxy)phosphinyl] uridine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-630 methoxyphenoxy)thiophosphin yl] uridine 3’-Deoxy-3’-fluoro-4’- I-631 difluoromethylcytidine 3’-Deoxy-3’-fluoro-4’- difluoromethylcytidine-5’-(O- I-632 phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylcytidine-5’-(O- I-633 phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’-fluoro-4’- difluoromethylcytidine-5’-(O- I-634 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylcytidine-5’-(O- I-635 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylcytidine-5’-(O- I-636 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylcytidine-5’-(O- I-637 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylcytidine-5’- I-638 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’-fluoro-4’- difluoromethylcytidine-5’- I-639 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-640 4-H-1,3,2- benzodioxaphosphorinyl)- cytidine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-(2- I-641 sulfideH-1,3,2- benzodioxaphosphorinyl)- cytidine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-642 methoxyphenoxy)phosphinyl] cytidine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-643 methoxyphenoxy)thiophosphin yl] cytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’-fluoro-4’- I-644 difluoromethylxylouridine 3’-Deoxy-3’-fluoro-4’- difluoromethylxylouridine-5’- I-645 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxylouridine-5’- I-646 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxylouridine-5’- I-647 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxylouridine-5’- I-648 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’-fluoro-4’- difluoromethylxylouridine-5’- I-649 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxylouridine-5’- I-650 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxylouridine-5’- I-651 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxylouridine-5’- I-652 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-653 4-H-1,3,2- benzodioxaphosphorinyl)- xylouridine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-(2- I-654 sulfideH-1,3,2- benzodioxaphosphorinyl)- xylouridine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-655 methoxyphenoxy)phosphinyl] xylouridine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-656 methoxyphenoxy)thiophosphin yl] xylouridine 3’-Deoxy-3’,5-difluoro-4’- I-657 difluoromethylxylouridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,5-difluoro-4’- difluoromethylxylouridine-5’- I-658 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,5-difluoro-4’- difluoromethylxylouridine-5’- I-659 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,5-difluoro-4’- difluoromethylxylouridine-5’- I-660 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,5-difluoro-4’- difluoromethylxylouridine-5’- I-661 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,5-difluoro-4’- difluoromethylxylouridine-5’- I-662 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,5-difluoro-4’- difluoromethylxylouridine-5’- I-663 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,5-difluoro-4’- difluoromethylxylouridine-5’- I-664 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 3’-Deoxy-3’,5-difluoro-4’- difluoromethylxylouridine-5’- I-665 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 3’-Deoxy-3’,5-difluoro-4’- difluoromethyl-5’-O-(2-oxido- I-666 4-H-1,3,2- benzodioxaphosphorinyl)- xylouridine 3’-Deoxy-3’,5-difluoro-4’- difluoromethyl-5’-O-(2- I-667 sulfideH-1,3,2- benzodioxaphosphorinyl)- xylouridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,5-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-668 methoxyphenoxy)phosphinyl] xylouridine 3’-Deoxy-3’,5-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-669 methoxyphenoxy)thiophosphin yl] xylouridine -Chloro-3’-deoxy-3’-fluoro- I-670 4’-difluoromethylxylouridine -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethylxylouridine- I-671 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethylxylouridine- I-672 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethylxylouridine- I-673 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethylxylouridine- I-674 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethylxylouridine- I-675 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethylxylouridine- I-676 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethylxylouridine- I-677 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethylxylouridine- I-678 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethyl-5’-O-(2- I-679 oxidoH-1,3,2- benzodioxaphosphorinyl)- xylouridine -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethyl-5’-O-(2- I-680 sulfideH-1,3,2- benzodioxaphosphorinyl)- xylouridine -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethyl-5’-O-[bis(4- I-681 methoxyphenoxy)phosphinyl] xylouridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethyl-5’-O-[bis(4- I-682 methoxyphenoxy)thiophosphin yl] xylouridine 3’-Deoxy-3’-fluoro-4’- I-683 difluoromethylxylocytidine 3’-Deoxy-3’-fluoro-4’- difluoromethylxylocytidine-5’- I-684 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxylocytidine-5’- I-685 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxylocytidine-5’- I-686 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’-fluoro-4’- difluoromethylxylocytidine-5’- I-687 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxylocytidine-5’- I-688 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxylocytidine-5’- I-689 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxylocytidine-5’- I-690 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’-fluoro-4’- difluoromethylxylocytidine-5’- I-691 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-692 4-H-1,3,2- benzodioxaphosphorinyl)- xylocytidine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-(2- I-693 sulfideH-1,3,2- benzodioxaphosphorinyl)- xylocytidine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-694 methoxyphenoxy)phosphinyl] xylocytidine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-695 methoxyphenoxy)thiophosphin yl] xylocytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’5-difluoro-4’- I-696 difluoromethylxylocytidine 3’-Deoxy-3’,5-difluoro-4’- difluoromethylxylocytidine-5’- I-697 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,5-difluoro-4’- difluoromethylxylocytidine-5’- I-698 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,5-difluoro-4’- difluoromethylxylocytidine-5’- I-699 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,5-difluoro-4’- difluoromethylxylocytidine-5’- I-700 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,5-difluoro-4’- difluoromethylxylocytidine-5’- I-701 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,5-difluoro-4’- difluoromethylxylocytidine-5’- I-702 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,5-difluoro-4’- difluoromethylxylocytidine-5’- I-703 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 3’-Deoxy-3’,5-difluoro-4’- difluoromethylxylocytidine-5’- I-704 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 3’-Deoxy-3’,5-difluoro-4’- difluoromethyl-5’-O-(2-oxido- I-705 4-H-1,3,2- benzodioxaphosphorinyl)- xylocytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,5-difluoro-4’- difluoromethyl-5’-O-(2- I-706 sulfideH-1,3,2- benzodioxaphosphorinyl)- xylocytidine 3’-Deoxy-3’,5-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-707 methoxyphenoxy)phosphinyl] xylocytidine 3’-Deoxy-3’,5-difluoro-4’- difluoromethyl-5’-O-[bis(4- I-708 methoxyphenoxy)thiophosphin yl] xylocytidine -Chloro-3’-deoxy-3’-fluoro- I-709 4’-difluoromethylxylocytidine -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethylxylocytidine- I-710 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethylxylocytidine- I-711 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethylxylocytidine- I-712 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethylxylocytidine- I-713 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethylxylocytidine- I-714 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethylxylocytidine- I-715 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethylxylocytidine- I-716 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethylxylocytidine- I-717 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethyl-5’-O-(2- I-718 oxidoH-1,3,2- benzodioxaphosphorinyl)- xylocytidine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-(2- I-719 sulfideH-1,3,2- benzodioxaphosphorinyl)- xylocytidine -Chloro-3’-deoxy -3’-fluoro- 4’-difluoromethyl-5’-O-[bis(4- I-720 methoxyphenoxy)phosphinyl] xylocytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-3’-deoxy 3’-fluoro- 4’-difluoromethyl-5’-O-[bis(4- I-721 methoxyphenoxy)thiophosphin yl] xylocytidine 3’-Deoxy-3’-fluoro-4’- I-722 difluoromethylxyloadenosine 3’-Deoxy-3’-fluoro-4’- difluoromethylxyloadenosine- I-723 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxyloadenosine- I-724 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxyloadenosine- I-725 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxyloadenosine- I-726 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’-fluoro-4’- difluoromethylxyloadenosine- I-727 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxyloadenosine- I-728 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxyloadenosine- I-729 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxyloadenosine- I-730 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-731 4-H-1,3,2- benzodioxaphosphorinyl)- xyloadenosine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-(2- I-732 sulfideH-1,3,2- benzodioxaphosphorinyl)- xyloadenosine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-733 methoxyphenoxy)phosphinyl] xyloadenosine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-734 methoxyphenoxy)thiophosphin yl] xyloadenosine 3’-Deoxy-3’-fluoro-4’- I-735 difluoromethylxyloguanosine 3’-Deoxy-3’-fluoro-4’- difluoromethylxyloguanosine- I-736 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxyloguanosine- I-737 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’-fluoro-4’- difluoromethylxyloguanosine- I-738 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxyloguanosine- I-739 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxyloguanosine- I-740 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxyloguanosine- I-741 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’-fluoro-4’- difluoromethylxyloguanosine- I-742 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’-fluoro-4’- difluoromethylxyloguanosine- I-743 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-(2-oxido- I-744 4-H-1,3,2- benzodioxaphosphorinyl)- xyloguanosine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-(2- I-745 sulfideH-1,3,2- benzodioxaphosphorinyl)- xyloguanosine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-746 methoxyphenoxy)phosphinyl] xyloguanosine 3’-Deoxy-3’-fluoro-4’- difluoromethyl-5’-O-[bis(4- I-747 methoxyphenoxy)thiophosphin yl] xyloguanosine I-748 4’-Difluoromethylxylouridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethylxylouridine- ’-(O-phenyl-N-(S) I-749 (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethylxylouridine- ’-(O-phenyl-N-(S) I-750 (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethylxylouridine- ’-(Onaphthyl-N-(S) I-751 (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethylxylouridine- ’-(Onaphthyl-N-(S) I-752 (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethylxylouridine- ’-(Onaphthyl-N-(S) I-753 (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethylxylouridine- ’-(Onaphthyl-N-(S) I-754 (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethylxylouridine- ’-{N,N’-bis[(S) I-755 (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 4’-Difluoromethylxylouridine- ’-{N,N’-bis[(S) I-756 (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-757 benzodioxaphosphorinyl)- xylouridine 4’-Difluoromethyl-5’-O-(2- sulfideH-1,3,2- I-758 benzodioxaphosphorinyl)- xylouridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl-5’-O- [bis(4- I-759 methoxyphenoxy)phosphinyl] xylouridine 4’-Difluoromethyl-5’-O- [bis(4- I-760 methoxyphenoxy)thiophosphin yl] xylouridine 4’-Difluoromethylxylouridine- I-761 3’,5’-cyclic phosphoric acid isopropyl ester 4’-Difluoromethylxylouridine- I-762 3’,5’-cyclic thiophosphoric acid isopropyl ester 4’-Difluoromethyl I-763 fluoroxylouridine 4’-Difluoromethyl fluoroxylouridine-5’-(O- I-764 phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl fluororxylouridine-5’-(O- I-765 phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl fluoroxylouridine-5’-(O I-766 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl fluoroxylouridine-5’-(O I-767 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl fluoroxylouridine-5’-(O I-768 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl fluoroxylouridine-5’-(O I-769 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl fluoroxylouridine-5’-{N,N’- I-770 bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 4’-Difluoromethyl fluororxylouridine-5’-{N,N’- I-771 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-772 benzodioxaphosphorinyl)- -fluoroxylouridine 4’-Difluoromethyl-5’-O-(2- sulfideH-1,3,2- I-773 benzodioxaphosphorinyl)- -fluoroxylouridine 4’-Difluoromethyl-5’-O- [bis(4- I-774 methoxyphenoxy)phosphinyl]- -fluoroxylouridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl-5’-O- [bis(4- I-775 methoxyphenoxy)thiophosphin yl]fluororxylouridine 4’-Difluoromethyl I-776 fluoroxylouridine-3’,5’-cyclic phosphoric acid isopropyl ester 4’-Difluoromethyl fluoroxylouridine-3’,5’-cyclic I-777 thiophosphoric acid isopropyl ester -Chloro-4’- I-778 difluoromethylxylouridine -Chloro-4’- difluoromethylxylouridine-5’- I-779 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-4’- difluoromethylxylouridine-5’- I-780 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-4’- difluoromethylxylouridine-5’- I-781 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-4’- difluoromethylxylouridine-5’- I-782 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-4’- difluoromethylxylouridine-5’- I-783 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-4’- difluoromethylxylouridine-5’- I-784 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-4’- difluoromethylxylouridine-5’- I-785 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate -Chloro-4’- difluoromethylxylouridine-5’- I-786 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate -Chloro-4’-difluoromethyl- ’-O-(2-oxidoH-1,3,2- I-787 benzodioxaphosphorinyl)- xylouridine -Chloro-4’-difluoromethyl- ’-O-(2-sulfideH-1,3,2- I-788 benzodioxaphosphorinyl)- xylouridine -Chloro-4’-difluoromethyl- ’-O-[bis(4- I-789 methoxyphenoxy)phosphinyl] xylouridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-4’-difluoromethyl- ’-O-[bis(4- I-790 methoxyphenoxy)thiophosphin yl] xylouridine -Chloro-4’- difluoromethylxylouridine- I-791 3’,5’-cyclic phosphoric acid isopropyl ester -Chloro-4’- difluoromethylxylouridine- I-792 3’,5’-cyclic thiophosphoric acid isopropyl ester I-793 4’-Difluoromethylxylocytidine Difluoromethylxylocytidine- I-794 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Difluoromethylxylocytidine- I-795 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number Difluoromethylxylocytidine- I-796 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Difluoromethylxylocytidine- I-797 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Difluoromethylxylocytidine- I-798 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Difluoromethylxylocytidine- I-799 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Difluoromethylxylocytidine- I-800 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number Difluoromethylxylocytidine- I-801 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 4’-Difluoromethyl-5’-O- [bis(4- I-802 methoxyphenoxy)phosphinyl] xylocytidine 4’-Difluoromethyl-5’-O- [bis(4- I-603 methoxyphenoxy)thiophosphin yl] xylocytidine 4’-Difluoromethyl-5’-O- [bis(4- I-804 methoxyphenoxy)phosphinyl] xylocytidine 4’-Difluoromethyl-5’-O- [bis(4- I-805 methoxyphenoxy)thiophosphin yl] xylocytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number Difluoromethylxylocytidine- I-806 3’,5’-cyclic phosphoric acid isopropyl ester Difluoromethylxylocytidine- I-807 3’,5’-cyclic thiophosphoric acid isopropyl ester 4’-Difluoromethyl I-808 fluoroxylocytidine 4’-Difluoromethyl fluoroxylocytidine-5’-(O- I-809 phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl fluororxylocytidine-5’-(O- I-810 phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl fluoroxylocytidine-5’-(O I-811 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl fluoroxylocytidine-5’-(O I-812 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl fluoroxylocytidine-5’-(O I-813 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethyl fluoroxylocytidine-5’-(O I-814 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethyl fluoroxylocytidine-5’-{N,N’- I-815 bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl fluororxylocytidine-5’-{N,N’- I-816 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 4’-Difluoromethyl-5’-O-(2- oxidoH-1,3,2- I-817 benzodioxaphosphorinyl)- -fluoroxylocytidine 4’-Difluoromethyl-5’-O-(2- sulfideH-1,3,2- I-818 benzodioxaphosphorinyl)- -fluoroxylocytidine 4’-Difluoromethyl-5’-O- [bis(4- I-819 methoxyphenoxy)phosphinyl]- -fluoroxylocytidine 4’-Difluoromethyl-5’-O- [bis(4- I-820 methoxyphenoxy)thiophosphin yl]fluororxylocytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl I-821 fluoroxylouridine-3’,5’-cyclic phosphoric acid isopropyl ester 4’-Difluoromethyl fluoroxylocytidine-3’,5’-cyclic I-822 thiophosphoric acid isopropyl ester -Chloro-4’- I-823 difluoromethylxylocytidine -Chloro-4’- difluoromethylxylocytidine-5’- I-824 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-4’- difluoromethylxylocytidine-5’- I-825 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-4’- difluoromethylxylocytidine-5’- I-826 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-4’- difluoromethylxylocytidine-5’- I-827 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-4’- difluoromethylxylocytidine-5’- I-828 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-4’- difluoromethylxylocytidine-5’- I-829 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-4’- difluoromethylxylocytidine-5’- I-830 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-4’- difluoromethylxylocytidine-5’- I-831 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate -Chloro-4’-difluoromethyl- ’-O-(2-oxidoH-1,3,2- I-832 benzodioxaphosphorinyl)- xylocytidine -Chloro-4’-difluoromethyl- ’-O-(2-sulfideH-1,3,2- I-833 benzodioxaphosphorinyl)- xylocytidine -Chloro-4’-difluoromethyl- ’-O-[bis(4- I-834 methoxyphenoxy)phosphinyl] xylocytidine -Chloro-4’-difluoromethyl- ’-O-[bis(4- I-835 methoxyphenoxy)thiophosphin yl] xylocytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-4’- difluoromethylxylocytidine- I-836 3’,5’-cyclic phosphoric acid isopropyl ester -Chloro-4’- difluoromethylxylocytidine- I-837 3’,5’-cyclic thiophosphoric acid isopropyl ester I-838 Difluoromethylxyloadenosine Difluoromethylxyloadenosine- I-839 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Difluoromethylxyloadenosine- I-840 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Difluoromethylxyloadenosine- I-841 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number Difluoromethylxyloadenosine- I-842 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Difluoromethylxyloadenosine- I-843 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Difluoromethylxyloadenosine- I-844 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Difluoromethylxyloadenosine- I-845 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Difluoromethylxyloadenosine- I-846 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl-5’-O- [bis(4- I-847 methoxyphenoxy)phosphinyl] xyloadenosine 4’-Difluoromethyl-5’-O- [bis(4- I-848 methoxyphenoxy)thiophosphin yl] xyloadenosine 4’-Difluoromethyl-5’-O- [bis(4- I-849 methoxyphenoxy)phosphinyl] xyloadenosine 4’-Difluoromethyl-5’-O- [bis(4- I-850 methoxyphenoxy)thiophosphin yl] xyloadenosine Difluoromethylxyloadenosine- I-851 3’,5’-cyclic phosphoric acid isopropyl ester Difluoromethylxyloadenosine- I-852 3’,5’-cyclic thiophosphoric acid isopropyl ester Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number I-853 Difluoromethylxyloguanosine Difluoromethylxyloguanosine- I-854 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Difluoromethylxyloguanosine- I-855 5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Difluoromethylxyloguanosine- I-856 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Difluoromethylxyloguanosine- I-857 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number Difluoromethylxyloguanosine- I-858 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Difluoromethylxyloguanosine- I-859 5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Difluoromethylxyloguanosine- I-860 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Difluoromethylxyloguanosine- I-861 5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 4’-Difluoromethyl-5’-O- [bis(4- I-862 methoxyphenoxy)phosphinyl] xyloguanosine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 4’-Difluoromethyl-5’-O- [bis(4- I-863 methoxyphenoxy)thiophosphin yl] xyloguanosine 4’-Difluoromethyl-5’-O- [bis(4- I-864 methoxyphenoxy)phosphinyl] xyloguanosine 4’-Difluoromethyl-5’-O- [bis(4- I-865 methoxyphenoxy)thiophosphin yl] xyloguanosine Difluoromethylxyloguanosine- I-866 3’,5’-cyclic phosphoric acid isopropyl ester Difluoromethylxyloguanosine- I-867 3’,5’-cyclic thiophosphoric acid isopropyl ester 3’-Deoxy-3’,3’-difluoro-4’- I-868 difluoromethyluridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyluridine-5’-(O- I-869 phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyluridine-5’-(O- I-870 phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyluridine-5’-(O- I-871 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyluridine-5’-(O- I-872 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyluridine-5’-(O- I-873 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyluridine-5’-(O- I-874 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyluridine-5’- I-875 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyluridine-5’- I-876 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl-5’-O-(2-oxido- I-877 4-H-1,3,2- benzodioxaphosphorinyl)- uridine 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl-5’-O-(2- I-878 sulfideH-1,3,2- benzodioxaphosphorinyl)- uridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-879 methoxyphenoxy)phosphinyl] uridine 3’-Deoxy-3’,3’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-880 methoxyphenoxy)thiophosphin yl] uridine 3’-Deoxy-3’,3’-difluoro-4’- I-881 difluoromethylfluorouridine 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluorouridine-5’-(O-phenyl-N- I-882 (S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluorouridine-5’-(O-phenyl-N- I-883 (S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluorouridine-5’-(O I-884 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluorouridine-5’-(O I-885 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluorouridine-5’-(O I-886 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluororuridine-5’-(O I-887 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluororuridine-5’-{N,N’- I-888 bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluorouridine-5’-{N,N’- I-889 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluorouridine-5’-O-(2-oxido I-890 H-1,3,2- benzodioxaphosphorinyl)- uridine 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluorouridine-5’-O-(2-sulfide- I-891 4-H-1,3,2- benzodioxaphosphorinyl)- uridine 3’-Deoxy-3’,3’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-892 methoxyphenoxy)phosphinyl]- -fluorouridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-893 methoxyphenoxy)thiophosphin yl]fluorouridine -Chloro-3’-deoxy-3’,3’- I-894 difluoro-4’- difluoromethyluridine -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethyluridine-5’-(O- I-895 phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethyluridine-5’-(O- I-896 phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethyluridine-5’-(O- I-897 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethyluridine-5’-(O- I-898 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethyluridine-5’-(O- I-899 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethyluridine-5’-(O- I-900 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethyluridine-5’- I-901 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethyluridine-5’- I-902 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethyluridine-5’-O- I-903 (2-oxidoH-1,3,2- benzodioxaphosphorinyl)- uridine -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethyluridine-5’-O- I-904 (2-sulfideH-1,3,2- benzodioxaphosphorinyl)- uridine -Chloro-3’-deoxy -3’,3’- difluoro -4’-difluoromethyl-5’- I-905 O-[bis(4- methoxyphenoxy)phosphinyl] uridine -Chloro-3’-deoxy -3’,3’- difluoro -4’-difluoromethyl-5’- I-906 O-[bis(4- methoxyphenoxy)thiophosphin yl] uridine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro-4’- I-907 difluoromethylcytidine 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylcytidine-5’-(O- I-908 phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylcytidine-5’-(O- I-909 phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylcytidine-5’-(O- I-910 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylcytidine-5’-(O- I-911 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylcytidine-5’-(O- I-912 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylcytidine-5’-(O- I-913 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylcytidine-5’- I-914 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylcytidine-5’- I-915 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl-5’-O-(2-oxido- I-916 4-H-1,3,2- benzodioxaphosphorinyl)- cytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl-5’-O-(2- I-917 sulfideH-1,3,2- benzodioxaphosphorinyl)- cytidine 3’-Deoxy-3’,3’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-918 methoxyphenoxy)phosphinyl] cytidine 3’-Deoxy-3’,3’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-919 methoxyphenoxy)thiophosphin yl] cytidine 3’-Deoxy-3’,3’-difluoro-4’- I-920 difluoromethyl fluorocytidine 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluorocytidine-5’-(O-phenyl- I-921 N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluorocytidine-5’-(O-phenyl- I-922 N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluorocytidine-5’-(O I-923 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluorocytidine-5’-(O I-924 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluorocytidine-5’-(O I-925 naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluororcytidine-5’-(O I-926 naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluororcytidine-5’-{N,N’- I-927 bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl fluorocytidine-5’-{N,N’- I-928 bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl-5’-O-(2-oxido- I-929 4-H-1,3,2- benzodioxaphosphorinyl)- -fluorocytidine 3’-Deoxy-3’,3’-difluoro-4’- difluoromethy -5’-O-(2- I-930 sulfideH-1,3,2- benzodioxaphosphorinyl)- -fluorocytidine 3’-Deoxy-3’,3’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-931 methoxyphenoxy)phosphinyl]- -fluorocytidine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-932 methoxyphenoxy)thiophosphin yl]fluorocytidine -Chloro-3’-deoxy-3’,3’- I-933 difluoro-4’- difluoromethylcytidine -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethylcytidine-5’-(O- I-934 phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethylcytidine-5’-(O- I-935 phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethylcytidine-5’-(O- I-936 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethylcytidine-5’-(O- I-937 1-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethylcytidine-5’-(O- I-938 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethylcytidine-5’-(O- I-939 2-naphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethylcytidine-5’- I-940 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethylcytidine-5’- I-941 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethylcytidine-5’-O- I-942 (2-oxidoH-1,3,2- benzodioxaphosphorinyl)- uridine -Chloro-3’-deoxy -3’,3’- difluoro-4’- difluoromethylcytidine-5’-O- I-943 (2-sulfideH-1,3,2- benzodioxaphosphorinyl)- uridine -Chloro-3’-deoxy -3’,3’- difluoro -4’-difluoromethyl-5’- I-944 O-[bis(4- methoxyphenoxy)phosphinyl] cytidine -Chloro-3’-deoxy -3’,3’- difluoro -4’-difluoromethyl-5’- I-945 O-[bis(4- methoxyphenoxy)thiophosphin yl] cytidine 3’-Deoxy-3’,3’-difluoro-4’- I-946 difluoromethyladenosine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylcytidine-5’-(O- I-947 phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyladenosine-5’- I-948 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyladenosine-5’- I-949 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyladenosine-5’- I-950 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyladenosine-5’- I-951 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyladenosine-5’- I-952 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyladenosine-5’- I-953 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyladenosine-5’- I-954 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl-5’-O-(2-oxido- I-955 4-H-1,3,2- benzodioxaphosphorinyl)- adenosine 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl-5’-O-(2- I-956 sulfideH-1,3,2- benzodioxaphosphorinyl)- adenosine Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-957 methoxyphenoxy)phosphinyl] adenosine 3’-Deoxy-3’,3’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-958 methoxyphenoxy)thiophosphin yl] adenosine 3’-Deoxy-3’,3’-difluoro-4’- I-959 difluoromethylguanosine 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylguanosine-5’- I-960 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylguanosine-5’- I-961 (O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylguanosine-5’- I-962 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylguanosine-5’- I-963 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylguanosine-5’- I-964 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylguanosine-5’- I-965 (Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylguanosine-5’- I-966 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]ph osphorodiamidate Table 1. Examples of compounds of generic Formula I.

Compound Structure Name Number 3’-Deoxy-3’,3’-difluoro-4’- difluoromethylguanosine-5’- I-967 {N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thi ophosphorodiamidate 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl-5’-O-(2-oxido- I-968 4-H-1,3,2- benzodioxaphosphorinyl)- guanosine 3’-Deoxy-3’,3’-difluoro-4’- difluoromethyl-5’-O-(2- I-969 sulfideH-1,3,2- benzodioxaphosphorinyl)- guanosine 3’-Deoxy-3’,3’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-970 methoxyphenoxy)phosphinyl] guanosine 3’-Deoxy-3’,3’-difluoro -4’- difluoromethyl-5’-O-[bis(4- I-971 methoxyphenoxy)thiophosphin yl] guanosine EXAMPLES Abbreviations used in this application include: acetyl (Ac), acetic acid (HOAc), azo- bis-isobutyrylnitrile (AIBN), 1-N-hydroxybenzotriazole (HOBt), atmospheres (Atm), high pressure liquid chromatography (HPLC), 9-borabicyclo[3.3.1]nonane (9-BBN or BBN), methyl (Me), tert-butoxycarbonyl (Boc), acetonitrile (MeCN), di-tert-butyl pyrocarbonate or boc anhydride (BOC O), 1-(3-dimethylaminopropyl)ethylcarbodiimide hydrochloride (EDCI), benzoyl (Bz), benzyl (Bn), m-chloroperbenzoic acid (MCPBA), butyl (Bu), methanol (MeOH), benzyloxycarbonyl (cbz or Z), melting point (mp), carbonyl diimidazole (CDI), MeSO - (mesyl or Ms), 1,4-diazabicyclo[2.2.2]octane (DABCO), mass spectrum (ms) diethylaminosulfur trifluoride (DAST), methyl t-butyl ether (MTBE), dibenzylideneacetone (Dba), N- carboxyanhydride (NCA), 1,5-diazabicyclo[4.3.0]nonene (DBN), N-bromosuccinimide (NBS), 1,8-diazabicyclo[5.4.0]undecene (DBU), N-methylmorpholine (NMM), N- methylpyrrolidone (NMP), 1,2-dichloroethane (DCE), pyridinium chlorochromate (PCC), N,N'- dicyclohexylcarbodiimide (DCC), pyridinium dichromate (PDC), dichloromethane (DCM), propyl (Pr), diethyl azodicarboxylate (DEAD), phenyl (Ph), di-iso-propylazodicarboxylate , DIAD, pounds per square inch (psi), di-iso-propylethylamine (DIPEA), pyridine (pyr), di-iso- butylaluminumhydride , DIBAL-H, room temperature, rt or RT, N,N-dimethyl acetamide (DMA), tert-butyldimethylsilyl or t-BuMe Si, (TBDMS), 4-N,N-dimethylaminopyridine (DMAP), triethylamine (Et N or TEA), N,N-dimethylformamide (DMF), triflate or CF SO - 3 3 2 (Tf), dimethyl sulfoxide (DMSO), trifluoroacetic acid (TFA), 1,1'-bis- (diphenylphosphino)ethane (dppe), 2,2,6,6-tetramethylheptane-2,6-dione (TMHD), 1,1'-bis- (diphenylphosphino)ferrocene (dppf), thin layer chromatography (TLC), ethyl acetate (EtOAc), tetrahydrofuran (THF), diethyl ether (Et O), trimethylsilyl or Me Si (TMS), ethyl (Et), p- toluenesulfonic acid monohydrate (TsOH or pTsOH), lithium hexamethyl disilazane (LiHMDS), 4-Me-C H SO - or tosyl (Ts), iso-propyl (i-Pr), N-urethane-N-carboxyanhydride (UNCA), 6 4 2 ethanol (EtOH). Conventional nomenclature including the prefixes normal (n), iso (i-), secondary (sec-), tertiary (tert-) and neo have their customary meaning when used with an alkyl moiety. (J. Rigaudy and D. P. Klesney, Nomenclature in Organic Chemistry, IUPAC 1979 Pergamon Press, Oxford.).

General Conditions Compounds of the invention can be made by a variety of methods depicted in the illustrative synthetic reactions described below in the Examples section.

The starting materials and reagents used in preparing these compounds generally are either available from commercial suppliers, such as Aldrich Chemical Co., or are prepared by methods known to those skilled in the art following procedures set forth in references such as Fieser and Fieser's Reagents for Organic Synthesis; Wiley & Sons: New York, 1991, Volumes 1- ; Rodd's Chemistry of Carbon Compounds, Elsevier Science Publishers, 1989, Volumes 1-5 and Supplementals; and Organic Reactions, Wiley & Sons: New York, 1991, Volumes 1-40. It should be appreciated that the synthetic reaction schemes shown in the Examples section are merely illustrative of some methods by which the compounds of the invention can be synthesized, and various modifications to these synthetic reaction schemes can be made and will be suggested to one skilled in the art having referred to the disclosure contained in this application.

The starting materials and the intermediates of the synthetic reaction schemes can be isolated and purified if desired using conventional techniques, including but not limited to, filtration, distillation, crystallization, chromatography, and the like. Such materials can be characterized using conventional means, including physical constants and spectral data.

Unless specified to the contrary, the reactions described herein are typically conducted under an inert atmosphere at atmospheric pressure at a reaction temperature range of from about -78 °C to about 150 °C, often from about 0 °C to about 125 °C, and more often and conveniently at about room (or ambient) temperature, e.g., about 20 °C.

Various substituents on the compounds of the invention can be present in the starting compounds, added to any one of the intermediates or added after formation of the final products by known methods of substitution or conversion reactions. If the substituents themselves are reactive, then the substituents can themselves be protected according to the techniques known in the art. A variety of protecting groups are known in the art, and can be employed. Examples of many of the possible groups can be found in "Protective Groups in Organic Synthesis" by Green et al., John Wiley and Sons, 1999. For example, nitro groups can be added by nitration and the nitro group can be converted to other groups, such as amino by reduction, and halogen by diazotization of the amino group and replacement of the diazo group with halogen. Acyl groups can be added by Friedel-Crafts acylation. The acyl groups can then be transformed to the corresponding alkyl groups by various methods, including the Wolff-Kishner reduction and Clemmenson reduction. Amino groups can be alkylated to form mono- and di-alkylamino groups; and mercapto and hydroxy groups can be alkylated to form corresponding ethers.

Primary alcohols can be oxidized by oxidizing agents known in the art to form carboxylic acids or aldehydes, and secondary alcohols can be oxidized to form ketones. Thus, substitution or alteration reactions can be employed to provide a variety of substituents throughout the molecule of the starting material, intermediates, or the final product, including isolated products.

The starting material 1 can be purchased through numerous vendors (CAS: 63593 3). Selective benzyl protection followed by oxidation, under Swern conditions, provided aldehyde intermediate 3. Fluorination with DAST, followed by treatment with acetic anhydride under acidic conditions provided the diacetate intermediate 5. Vorbrüggen reaction followed by deprotection, under standard conditions, provided 4’-difluoromethyluridine 7 (Scheme 1).

Scheme 1 Compound 8 can be prepared, from the uridine analogue 7, by those skilled in the art of organic synthesis following the synthetic sequence outlined below (Scheme 2).

Scheme 2 Phosphoramidate compounds of the present invention can be prepared by condensation of nucleoside 7, 8 or 9 with a suitably substituted phosphochloridate, or its sulfur analogue, of type 10 in the presence of a strong base (Scheme 3). The coupled product 11 of formula I is obtained as a mixture of two diastereomers initially under the coupling reaction and can be separated into their corresponding chiral enantiomers by chiral column, chiral HPLC, or chiral SFC chromatography.

Scheme 3 Phosphorodiamidate compounds of formula I in the present invention can be prepared by condensation of nucleoside 7, 8 or 9 with a suitably substituted phosphorodiamidic chloride, or phosphorodiamidothioic chloride, of type 12 in the presence of a strong base (Scheme 4).

Scheme 4 Cyclic phosphates of the present invention can be prepared by condensation of nucleoside 4 or 5 with isopropyl N,N,N,N-tetraisopropylphosphorodiamidite 14 (Scheme 5).

Conversion to the thio derivative can be performed by heating the crude reaction mixture with bis(3-triethoxylsilyl)propyl-tetrasulfide (TEST).

Scheme 5 An alternative cyclic phosphate can be furnished from the reaction of the nucleoside 7, 8 or 9 with the appropriate chlorophosphite 16 in the presence of a base and Oxone (Scheme 6).

Scheme 6 Phosphate prodrugs of type 19 are readily prepared from the reaction of compounds 7, 8 or 9 with chlorophosphates of type 18 (Scheme 7).

Scheme 7 The synthesis of 4’-difluoromethylguanidine is outlined in Scheme 8. Herein, the ribose intermediate 5 undergoes a Vorbrüggen reaction with 20 to give the guanidine 23 derivative, following deprotection.

Scheme 8 The synthesis of 4’-difluoromethyladenosine is outlined in Scheme 9. Herein, the ribose intermediate 5 undergoes a Vorbrüggen reaction with 24 to give the adenosine derivative 27, following deprotection.

Scheme 9 Synthesis of 4’-difluoromethylchlorocytidine is outlined in Scheme 10. Herein, the ribose intermediate 5 undergoes a Vorbrüggen reaction with 28 to give the cytidine derivative 31, following deprotection.

Scheme 10 4’-Difluoromethylaracytidine synthesis is outlined in Scheme 11. Herein, the uridine intermediate 6 is reacted with diphenyl carbonate to provide the anhydro compound 33.

Hydrolysis and deprotection yield the arabinocytidine 38, following deprotection.

Scheme 11 The arabinouridine intermediate 34 was converted to its 2’-deoxy-2’-fluoro derivative 39 through a reaction with DAST. Subsequent base conversion and deprotection provides the 2’- deoxy-2’-fluorocytidine 41 (Scheme 12).

Scheme 12 The phosphoramidate compound 47 was synthesized following standard coupling methods as shown in Scheme 13. The neopently ester derivative was synthesized in a similar manner and outlined in Scheme 14.

Scheme 13.

Scheme 14.

General Preparations Synthesis of compound ((3aR,5R,6S,6aR)(benzyloxy)(benzyloxymethyl)-2,2 -dimethyl- tetrahydrofuro[2,3-d][1,3]dioxolyl)methanol (2) To a solution of compound 1 (0.5 g, 1.61 mmol) in dry DMF (20 mL), was added NaH (77.6 mg, 1.94 mmol). After the mixture stirred at room temperature for 0.5 h, BnBr (355 mg, 2.09 mmol) was added drop-wise. The mixture was allowed to stir at r.t. for 4 hrs. TLC (Petroleum ether:Ethyl acetate; 1:3) showed the reaction was complete. The reaction was quenched with water and extracted with ethyl acetate. The organic phase was dried over Na SO and then evaporated to dryness under reduced pressure. Purification by silica gel chromatography [ethyl acetate:petroleum ether (1:10 to 1:3)] provided the product 2 (0.42 g, 65%) as a colorless oil. LC-MS (M+H) = 401.0 Synthesis of compound (3aR,5R,6S,6aR)(benzyloxy)(benzyloxymethyl)-2,2 -dimethyl- tetrahydrofuro[2,3-d][1,3]dioxolecarbaldehyde (3) DMSO (1.65 mL, 23.6 mmol) was added drop-wise to a cold (–78 C) solution of oxalyl chloride (1.05mL, 12.0mmol) in dichloromethane (50 mL). After stirring for 30 min, a solution of compound 2 (3 g, 7.5 mmol) in dichloromethane (25 mL) was added to the reaction. The stirring was continued for 45 min at –78 C, and triethylamine (3.5 mL, 25.0 mmol) was added to the reaction. The reaction was stirred at –78 C for 15 min, after which the ice-bath was removed and the reaction was allowed to gradually warm over 45 min. The reaction was diluted with dichloromethane and the organic phase was sequentially washed with 5% aqueous HCl solution, saturated aqueous NaHCO solution, brine, dried (Na SO ) and concentrated under reduced 3 2 4 pressure to provide 3 (2.2 g, crude), which was used without any further purification. LC-MS (M+H) = 399.1 Synthesis of compound (3aR,5R,6S,6aR)(benzyloxy)(benzyloxymethyl)-5 - (difluoromethyl)-2,2-dimethyl-tetrahydrofuro[2,3-d][1,3]dioxole (4) To a solution of compound 3 (2.2 g, 5.5 mmol) in dichloromethane (20 mL) was added DAST (4.45 g, 27.6 mmol). The mixture was stirred at room temperature for 14 hrs and then quenched by the addition of saturated NaHCO , extracted with EtOAc, dried (Na SO ) and 3 2 4 purified by silica gel chromatography [ethyl acetate:petroleum ether (1:10)] to afford 4 (1.0 g, 43%) as an oil. LC-MS (M+H) = 421.1 Synthesis of (3R, 4S, 5R)(benzyloxy)(benzyloxymethyl)(difluoromethyl)- tetrahydrofuran-2,3-diyl diacetate (5) To a solution of compound (3aR,5R,6S,6aR)(benzyloxy)(benzyloxymethyl)-5 - (difluoromethyl)-2,2-dimethyl-tetrahydrofuro[2,3-d][1,3]dioxole (1.0 g, 6.3 mmol) in Ac2O (2.5 mL) and AcOH (10 mL) was added H2SO4 (3 drops). The mixture was stirred at room temperature for 3 hrs. TLC showed the reaction was complete. The mixture was poured to water, extracted with EtOAc , dried (Na2SO4) and purified by silica gel chromatography [ethyl acetate:petroleum ether (1:3)] to afford compound 5 (1.0 g, crude) as a light-color oil. LC-MS (M+H)+ = 465.1 Synthesis of compound(2R,3R,4S,5R)(benzyloxy)(benzyloxymethyl)(difluorom - ethyl)(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-tetrahydrofuranyl acetate (6) The mixture of uracil (482 mg, 4.32 mmol) and BSA (1.75 g, 8.64 mmol) in MeCN (20 ml) was stirred at room temperature for 3 hrs. Compound 5 (1.0 g, 2.16 mmol) and SnCl (2.4 g, 9.3 mmol) was added respective, then stirred at 65 °C for 12 hrs. The mixture was quenched with saturated NaHCO solution, extracted with EtOAc (200 mL × 3), dried over Na SO and purified by silica gel chromatography [ethyl acetate:petroleum ether (1:10)] to afford the product (450 mg, 40%) as a yellow solid. LC-MS (M+H) = 517.1 Synthesis of compound 1-((2R,3R,4S,5R)(difluoromethyl)-3,4-dihydroxy-5 - (hydroxymethyl)-tetrahydrofuranyl)pyrimidine-2,4(1H,3H)-dione (7) The mixture of compound 1-((2R,3R,4S,5R)(benzyloxy)(benzyloxymethyl)-5 - (difluoromethyl)hydroxy-tetrahydrofuranyl)pyrimidine-2,4(1H,3H)-dione (450 mg 0.87 mmol) in CH3CN (10 mL) was added NH3.H2O (10 mL) stirred at room temperature overnight.

The mixture was concentrated and concentrated and dissolved in methanol (30mL). To this was added Pd(OH) /C (1.0g). The reaction mixture was stirred under an atmosphere of hydrogen and at room temperature overnight, the mixture was concentrated and purified by Prep-HPLC to afford 7 (100 mg, 40%) as white solid. LC-MS (M+H) = 295.0 H NMR (300 MHz, DMSO-d6): δ 11.42 (s, 1H), 7.89–7.86 (d, 1H, J = 8.1 Hz), 6.30–5.94 (m, 2H), 5.78–5.64 (m, 2H), 5.56–5.51 (m, 2H), 4.31–4.25 (m, 1H), 4.21–4.18 (m, 1H), 3.75–3.71 (m, 1H), 3.62–3.57 (m, 1H).

Synthesis of compound4-amino((2R,3R,4S,5R)(difluoromethyl)-3,4-dihydroxy (hydroxymethyl)-tetrahydrofuranyl)pyrimidin-2(1H)-one （8） To a solution of 7 (0.1 g, 0.34 mmol) in dry pyridine (15 mL) was added Ac O (5 mL). The mixture was stirred at room temperature overnight and then evaporated to dyness under reduced pressure. The residue was treated with saturated aqueous NaHCO solution extracted with ethyl acetate. The organic phase was separated, dried (Na SO ) and evaporated to dryness under reduced pressure. Puriication by silica gel chromatography [ethyl acetate:petroleum ether (1:10)] gave the acetylated intermediate (0.12 g, 84%) as a white solid.

MS [M+H] = 420.1. The acetylated intermediate (0.12 g, 0.286 mmol) and 1H-tetrazole (0.02 g, 0.429 mmol) were azeotroped with pyridine and then dissolved in anhydrous pyridine (20 mL).

The solution was cooled by an ice-water bath, and 4-chlorophenylphosphorodichloridate (84 mg, 0.343 mmol) was added. The reaction mixture was stirred at 0-5 °C for 5 min and then allowed to warm to room temperature. After 5 h, the reaction mixture was evaporated to dryness under reduced pressure and the residue was partitioned between CH Cl and saturated aqueous NaHCO solution. The organic phase was separated, dried (Na SO ), and evaporated to dryness 3 2 4 under reduced pressure. The crude product was treated with NH .H O (10 mL) in 1,4-dioxane (20 mL) for 16 h at room temperature and then evaporated to dryness under reduced pressure.

The crude material was dissolved in NH in MeOH (7N, 30 mL) and the mixture was stirred for 18 h at room temperature and then evaporated to dryness under reduced pressure. Purification by preparative HPLC column purification gave 8 (51 mg, 61%) as a white solid. MS [M+H] = 294.0 H NMR (300 MHz, DMSO-d6)  7.80–7.78 (d, J=7.8Hz, 1H), 7.28–7.24 (brs, 2H), 6.28–5.92 (m, 2H), 5.81–5.78(d, J=7.5Hz, 1H), 5.53–5.38 (m, 3H), 4.30–4.19 (m, 2H), 3.68–3.60 (m, 2H).

Synthesis of compound (2R,3R,4S,5R)(benzyloxy)(benzyloxymethyl)(difluoro methyl)(2-isobutyramidooxo-1,6-dihydropurinyl)-tetrahydrofuranyl acetate (21) To a solution of compound N-(6-oxo-6,9-dihydro-1H-purinyl)isobutyramide (0.57 g, 2.58 mmol) in anhydrous CH CN (50 mL) was added BSA (1.26 mL, 5.17 mmol) portion- wise while maintaining the reaction temperature at 25 °C. Then the reaction was stirred at 40 °C for 1 h until a clear solution persisted. Compound 5 (0.6 g, 1.29 mmol) in CH CN (5 mL) was added into the mixture at 0 °C followed by TMSOTf (0.94 mL, 5.17 mmol). The mixture was stirred at 40 °C for 2 h and then poured into saturated NaHCO solution (10 mL) at 0 °C, extracted with ethyl acetate, washed with water, brine solution, dried over Na SO and evaporated to dryness under reduced pressure. The crude compound was purified by silica gel chromatography [petroleum ether:ethyl acetate (5:1 to 1:1)] to provide the product 21 as a white foam (0.5 g, 60%). LC-MS: (M+H) = 626 Synthesis of compound 2-amino((2R,3R,4S,5R)(benzyloxy)(benzyloxymethyl) (difluoromethyl)hydroxy-tetrahydrofuranyl)-1H-purin-6(9H)-one (22) A mixture of compound 21 (0.5 g, crude) in NH ·MeOH (7 N, 40 mL) was stirred at °C for 16 h and then evaporated to dryness. Purification by silica gel chromatography [dichloromethane:methanol (100:1 to 20:1)] to give the product 22 as a white foam (0.22 g, 53%). LC-MS (M+H) = 514 Synthesis of compound 2-amino((2R,3R,4S,5R)(difluoromethyl)-3,4-dihydro xy (hydroxymethyl)-tetrahydrofuranyl)-1H-purin-6(9H)-one (23) To a solution of compound 22 (0.22 g, 0.42 mmol) in methanol (30 mL) was added HCO NH (600 mg, 9.52 mmol), followed by Pd(OH) /C (500 mg). The reaction mixture was 2 4 2 stirred at 80 °C for 15 h, then cooled to 25 °C, filtered and then evaporated to dryness under reduced pressure. Purification by silica gel chromatography [dichloromethane:methanol (20:1 to :1)] and prep-HPLC provided the product 23 (0.046 g, 33%) as a white solid. LC-MS (M+H) = 334.1 H NMR (300MHz, d -DMSO) δ 10.64 (s, 1 H), 7.93 (s, 1 H), 6.50 (s, 2 H), 6.28–5.92 (dd, J = 52.8, 56.4 Hz, 1 H), 5.87–5.83 (d, J = 14.7 Hz, 1 H), 5.62–5.45 (m, 3 H), 4.73–4.67 (m, 1 H), 4.27–4.24 (m, 1 H), 3.72–3.58 (m, 2 H).

Synthesis of (2R,3R,4S,5R)(6-benzamido-9H-purinyl)(benzyloxy)(benz yloxymethyl)(difluoromethyl)-tetrahydrofuranyl acetate (25) To a solution of compound 5 (1.44 g, 6.02 mmol) in anhydrous CH CN (15 mL) was added BSA (7.2 mL, 30.1 mmol) portion-wise while maintaining the reaction temperature at 25 °C. After the reaction mixture became clear, compound 1 (0.4 g, 0.86 mmol) in CH CN (5 mL) and SnCl (0.42 mL, 3.5 mmol) was added into the mixture. The mixture was stirred at 85 °C for h, then it was poured into saturated NaHCO (10 mL) at 0 °C, extracted with ethyl acetate, the combined organic layer was washed with H O (100 mL), brine solution (100 mL), dried over Na SO and evaporated to dryness. Purification by silica gel chromatography column [dichloromethane:methanol; (30:1)] to give product 25 as an colorless oil (0.225 g, 25%). LC- MS: (M+H) = 393 Synthesis of (2R,3R,4S,5R)(6-amino-9H-purinyl)(benzyloxy)(benzyloxy methyl)- -(difluoromethyl)-tetrahydrofuranol (26) A mixture of compound 25 (0.225 g, 0.35 mmol) in NH ·MeOH (40 mL) was stirred in a sealed tube at 65 °C for 16 hrs, warmed to 25 °C and stirred for 3 hrs. TLC showed the reaction was completed, the reaction solution was concentrated and the crude compound was purified by silica gel chromatography column [dichloromethan:methanol (30:1)] to give product 26 as an colorless oil (0.16 g, 92%).

LC-MS (M+H) = 469 Synthesis of (2R,3S,4R,5R)(6-amino-9H-purinyl)(difluoromethyl)(hydroxyl methyl)-tetrahydrofuran-3,4-diol (27) Concentrated HCl (37%) 1 drop was added into the mixture of compound 3 (0.048 g, 0.1 mmol) and Pd(OH) /C (0.8g) in MeOH (5 mL), after addition, the whole mixture was stirred at 25 °C under hydrogen atmosphere. After 2 h, the reaction mixture was filtered and evaporated to dryness under reduced pressure. Purification by prep-HPLC afforded 27 (0.024 g, 85%) as a white solid. L-MS (M+H) = 318.

H NMR (300 MHz, d -DMSO) δ 8.52 (s, 1 H), 8.24 (s, 1 H), 6.94 (br s, 2 H), 6.47–6.11 (m, 1 H), 5.99 (d, J = 7.8 Hz, 1 H), 5.81–5.79 (m, 2 H), 5.59 (br s, 1 H), 4.46 (br s, 1 H), 4.32 (br s, 1 H), 3.74 (br s, 1 H), and 3.65 (br s, 1 H).

Synthesis of (2R,3R,4S,5R)(4-aminochlorooxopyrimidin-1(2H)-yl)(benzy loxy)- -(benzyloxymethyl)(difluoromethyl)-tetrahydrofuranyl acetate (29).

To a solution of 4-aminochloropyrimidin-2(1H)-one 28 (0.336 g, 2.33 mmol) in anhydrous CH CN (10 mL) was added BSA (0.945 g, 4.64 mmol) portion-wise while maintaining the reaction temperature at 25 °C. After the reaction mixture became clear, compound 5 (0.54 g, 1.16 mmol) in CH CN (2 mL) and SnCl (1.2 g, 4.64 mmol) was added into the mixture. The mixture was stirred at 65 °C for 1 h, then cooled and poured into saturated NaHCO3 solution (20 mL).

The organic phase was extracted with ethyl acetate, washed with water, brine, dried (Na SO ) and evaporated to dryness under reduced pressure. Purification by flash silica gel chromatography [dichloromethane:methanol (40:1)] gave 29 as a white solid (0.24 g, 31%).

LC-MS: (M+H) = 550.1 Synthesis of 4-amino((2R,3R,4S,5R)(benzyloxy)(benzyloxymethyl)(diflu oromethyl)hydroxy-tetrahydrofuranyl)chloropyrimidin-2(1H)-one (30).

A mixture of compound 29 (0.235 g, 0.43 mmol) in NH MeOH (10 mL) was stirred at r.t for 3 h and then evaporated to dryness under reduced pressure. Purification by silica gel chromatography column [dichloromethane:methanol (40:1)] gave 30 as a white solid (0.135 g, 62%). LC-MS: (M+H) = 508.1 Synthesis of 4-aminochloro((2R,3R,4S,5R)(difluoromethyl)-3,4-dihydro xy (hydroxymethyl)-tetrahydrofuranyl)pyrimidin-2(1H)-one (31) BCl (2.46 mL, 2.46 mmol) was added to a cooled (–78 °C) solution of compound 30 (0.125 g, 0.246 mmol) in dry dichloromethane (10 mL). The mixture was cooled to 0 °C and pyridine (0.5 mL) and MeOH (2 mL) were added. The reaction mixture was evaporated to dryness under reduced pressure. Purification by prep-HPLC provided 31 (0.035 g, 44 %) as a white solid. LC-MS (M+H) = 328.1 H NMR (300 MHz, DMSO-d ) δ 8.12 (s, 1 H), 7.99 (s, 1 H), 7.35 (s, 1 H), 6.27–5.91 (m, 2 H), .57 (m, 2 H), 5.44–5.42 (d, J = 6.3 Hz, 1 H), 4.25–4.16 (m, 2 H), 3.62 (m, 2 H).

Synthesis of 1-((2R,3R,4S,5R)(benzyloxy)(benzyloxymethyl)(difluoromethyl) hydroxy-tetrahydrofuranyl)pyrimidine-2,4(1H,3H)-dione (32).

A solution of compound 6 (0.52 g, 1 mmol) in NH ·MeOH/dioxane (6 mL/6 mL) was stirred at 20 °C. After 18 h the reaction mixture was evaporated to dryness under reduced pressure. Purification by silica gel chromatography [petroleum ether:ethyl acetate (4:1 to 1.5:1)] provided 32 (0.314 g, 61%) as a white solid.

LC-MS: (M+H) = 475.1 Synthesis of 2,2’-anhydro- 4’-difluoromethyl(-arabinofuranosyl)uracil (33).

Diphenyl carbonate (0.258 g, 1.2 mmol) and sodium hydrogen carbonate (0.184 g, 2.2 mmol) were added to a solution of 32 (0.52 g, 1.1 mmol) in dry DMF (10 mL). The reaction mixture was stirred at 110 °C for 2 h, then cooled and evaporated to dryness under reduced pressure. The residue was dissolved with dichloromethane and washed with water, brine, dried (Na SO ) and then evaporated to dryness under reduced pressure to give the crude product 33 (0.45 g) as a white solid, which was used directly without further purification. LC-MS: (M+H) = 457.2 Synthesis of 1-((2R,3S,4S,5R)(benzyloxy)(benzyloxymethyl)(difluoromethyl) hydroxy-tetrahydrofuranyl)pyrimidine-2,4(1H,3H)-dione (34).

A solution of aqueous NaOH (1N, 5 mL) was added to a solution of compound 33 (0.45 g) in ethanol (10 mL). After stirring at 20 °C for 3 h, the reaction mixture was adjusted to pH = 7 by strong-acid cation-exchange resin, filtered and evaporated to dryness under reduced pressure. Purification by silica gel chromatography [dichlormethane:methanol (40:1)] provided 34 (0.12 g, 25%) as a white solid. LC-MS: (M+H) = 475.2 Synthesis of (2R,3S,4S,5R)(benzyloxy)(benzyloxymethyl)(difluoromethyl)(2,4- dioxo-3,4-dihydropyrimidin-1(2H)-yl)-tetrahydrofuranyl acetate (35).

Ac O (0.5 mL) was added into a solution of compound 34 (0.114 g, 0.24 mmol) in dry pyridine (4 mL). The reaction mixture was stirred at 20 °C for 3 h and then quenched by saturated aqueous NaHCO solution (2 mL). The organic phase was extracted with dichloromethane and then evaporated to dryness under reduced pressure. Purification by silica gel chromatography [petroleum ether:ethyl acetate (4:1)] afforded 35 (0.12 g, 88%) as a white solid. LC-MS: (M+H) = 517.2 Synthesis of (2R,3S,4S,5R)(4-aminooxopyrimidin-1(2H)-yl)(benzyloxy) (benzyloxymethyl)(difluoromethyl)-tetrahydrofuranyl acetate (36). 4-Chlorophenylphosphonic dichloride (0.4 g, 0.81 mmol) was added to a cooled (0 °C) solution of 1-H-tetrazole (0.056 g, 0.81 mmol) and 35 (0.113 g, 0.22 mmol) in dry pyridine (5 mL). The reaction mixture was left to stir under a nitrogen atmosphere at 20 °C for 3 h and then evaporated to dryness under reduced pressure. The residue was dissolved in dioxane and NH ·H O (5 mL) was added. After stirring for 5 h at 20 °C, the reaction mixture was evaporated to dryness under reduced pressure to afford 36 (0.2 g, crude).

Synthesis of 4-amino((2R,3S,4S,5R)(benzyloxy)(benzyloxymethyl) (difluoromethyl)hydroxy-tetrahydrofuranyl)pyrimidin-2(1H)-one (37).

A solution of compound 36 (0.112 g, 0.21 mmol) in NH ·MeOH (4 mL) was stirred at 60 °C for 12 h and then cooled and evaporated to dryness under reduced pressure to give 37 as a white solid. LC-MS: (M+H) = 474.2 Synthesis of 4-amino((2R,3S,4S,5R)(difluoromethyl)-3,4-dihydroxy (hydroxymethyl)-tetrahydrofuranyl)pyrimidin-2(1H)-one (38).

BCl (3.7 mL, 3.7 mmol) was added to a solution of compound 37 (0.175 g, 0.37 mmol) in dichloromethane (10 mL) cooled to –78 °C. The reaction was stirred at –78 °C for 3 h, then warmed to 25 °C and stirred for a further 12 h. The reaction mixture was cooled to 0 °C and then pyridine was added into the mixture, followed by methanol. The reaction mixture was evaporated to dryness under reduced pressure. Purification by prep-HPLC afforded the product 38 (0.052 g, 41 %) as a white solid. LC-MS (M+H) = 294.1 H NMR (300MHz, DMSO-d6) δ 7.59–7.56 (d, J = 7.5 Hz, 1 H), 7.13–7.06 (d, J = 21.3 Hz, 2 H), 6.24–6.23 (d, J = 5.7 Hz, 1 H), 6.07 (s, 1 H), 5.92-5.90 (d, J = 5.1 Hz, 1 H), 5.67–5.62 (m, 2 H), .41–5.38 (m, 1 H), 4.30–4.28 (m, 1 H), 4.15–4.14 (m, 1 H), 3.64–3.59 (m, 2 H).

Synthesis of compound 1-((2R,3R,4R,5R)(benzyloxy)(benzyloxymethyl)(difluo romethyl)fluoro-tetrahydrofuranyl)pyrimidine-2,4(1H,3H)-dione (39).

Diethylaminosulfur trifluoride (7.6 g, 47.4 mmol) was added to a suspension of compound 34 (1.5 g, 3.16 mmol) in dry THF (150 mL). The mixture was stirred at 60 °C for 16 h and then cooled to room temperature. The mixture was quenched by the addition of saturated aqueous NaHCO solution and then extracted with ethyl acetate. The organic phase was washed with brine, dried (Na SO ) and evaporated to dryness under reduced pressure. Purification by silica gel chromatography [petroleum ether:ethyl acetate (4:1)] afforded 39 as a brown solid (700 mg, 46%). LC-MS (M+H) = 477.4 Synthesis of compound 4-amino((2R,3R,4R,5R)(benzyloxy)(benzyloxymeth yl) (difluoromethyl)fluoro-tetrahydrofuranyl)pyrimidin-2(1H)-one (40). 4-Chlorophenyl phosphorodichloridate (0.68 g, 2.77 mmol) was added to a solution of compound 39 (0.22 g, 0.462 mmol) and 1-H-tetrazole (0.485 g, 6.93 mmol) in dry pyridine (100 mL) at 0 °C. After stirring at room temperature for 3 h, the reaction mixture was evaporated to dryness under reduced pressure. The residue was dissolved in dichloromethane and washed with saturated aqueous NaHCO solution, brine, dried (Na SO ) and evaporated to dryness under 3 2 4 reduced pressure. Purification by silica gel chromatography (petroleum ether:ethyl acetate (4:1)] provided the intermediate as an red oil. The intermediate was dissolved in dioxane (40 mL) and NH •H O (2 mL) was added. After stirring for 30 min, the reaction mixture was evaporated to dryness under reduced pressure. Purification by silica gel chromatography [dichloromethane:methanol (10:1)] provided 40 as a brown solid (180 mg, 81%).

LC-MS (M+H) = 476.1 Synthesis of compound 4-amino((2R,3R,4R,5R)(difluoromethyl)fluorohydro xy- -(hydroxymethyl)-tetrahydrofuranyl)pyrimidin-2(1H)-one (41).

A mixture of compound 40 (160 mg, 0.34 mmol), Pd(OH) /C (0.8 g) and concentrated aqueous HCl (2 drops, 37%) in methanol (10 mL) was stirred under an atmosphere of hydrogen for 10 min, filtered and evaporated to dryness under reduced pressure. Purification by preparative HPLC afforded 41 as a white solid (26 mg, 25%). LC-MS (M+H) = 296.1 H NMR (300MHz, d -DMSO) δ 7.79 (d, J = 7.2 Hz, 1 H), 7.33 (d, J = 10.4 Hz, 2 H), 6.26–5.99 (m, 3 H), 5.77 (d, J = 7.6 Hz, 1 H), 5.44 (t, J = 5.2 Hz, 1 H), 5.15 (dt, J = 53.6 Hz, J = 5.2 Hz, 1 H), 4.58–4.53 (m, 1 H), 3.70–3.58 (m, 2 H).

Synthesis of (S)(benzyloxy)oxopropanaminium chloride (43).

Thionyl chloride (27 mL) was added drop-wise to a solution L-alanine (42) (6.83 g, 76.6 mmol) in benzyl alcohol (120 mL). After stirring at 0 °C for 2 h, the reaction mixture was warmed to room temperature and stirred for a further 24 h and then evaporated to dryness under reduced pressure. Trituration with diethyl ether, followed by filtration and evaporation under reduced pressure, provided the crude product 43 (3.5 g), which was used directly without further purification. LC-MS (M-Cl) = 180 Synthesis of (2S)-benzyl 2-(chloro(phenoxy)phosphorylamino)propanoate (44).

Phenyl phosphorodichloridate (1.17 g, 2 N) was added to a solution of 43 (1 g, 5.58 mmol) in dichloromethane at –78 °C. Triethylamine (1.13 g, 11.173 mmol) was then added drop- wise. Once complete, the reaction mixture was allowed to warm to room temperature and then evaporated to dryness under reduced pressure. Purification by silica gel chromatography [petroleum ether:ethyl acetate (3:1)] provided 44 as an colorless oil (1.2 g, 60%). LC-MS (M+H) = 354 Synthesis of compound (45).

To a mixture of compound 8 (0.11 g, 0.375 mmol) and compound 1,1- dimethoxycyclopentane (0.495 g, 3.8 mmol) in dichloromethane was added PTSA (0.01 g). The resulting mixture was stirred at 65 °C for 1 h and then evaporated to dryness under reduced pressure. Purification by silica gel chromatography [dichloromethane:methanol (10:1)] afforded 45 as a white solid (0.17 g, 90%). LC-MS (M+H) = 360.2 Synthesis of compound (46).

To a suspension of compound 45 (0.08 g, 0.223 mmol) in dry THF was added t- BuMgBr (1.3 mL, 1.34 mmol) at 0 °C under nitrogen atmosphere, then warmed to 25 °C and stirred for 30 min. The reaction mixture was then cooled to 0 °C and then (2S)-Benzyl 2- (chloro(phenoxy)phosphorylamino)propanoate (0.236 g, 0.668 mmol) was added drop-wise. The reaction mixture was stirred at room temperature for 2 h and then quenched by the addition of methanol (1 mL). The mixture was then evaporated to dryness under reduced pressure.

Purification by silica gel chromatography [dichloromethane:methanol (10:1)] afforded 46 as a white solid (0.19 g). LC-MS (M+H) = 677.1 Synthesis of compound (S)-benzyl 2-((((2R,3S,4R,5R)(4-aminooxopyrimid in-1(2H)- yl)(difluoromethyl)-3,4-dihydroxy-tetrahydrofuran yl)methoxy)(phenoxy)phosphorylamino)propanoate (47).

A solution of compound 46 (0.18 g, 0.26 mmol) in formic acid (80%, v/v) was stirred at 25 °C for 18 h and then evaporated to dryness under reduced pressure. Purification by prep- HPLC provided 47 as a white solid (12.8 mg, 5%). LC-MS (M+H) = 611.1 H NMR (300MHz, DMSO-d ) δ 7.55–7.16 (m, 13 H), 6.33–5.97 (m, 3 H), 5.78–5.77 (m, 2 H), .47–5.46 (m, 1 H), 5.15–5.06 (m, 2 H), 4.23–3.95 (m, 5 H), 1.28–1.23 (t, J = 7.5 Hz, 3 H).

Synthesis of compound (49).

To a suspension of compound 45 (0.2 g, 0.5 mmol) in dry THF was added t-BuMgBr (3 mL, 3 mmol) at 0 °C under nitrogen atmosphere, then warmed to 25 °C and stirred for 30 min, compound (2S)-neopentyl 2-(chloro(phenoxy)phosphorylamino)propanoate (0.5 g, 1.5 mmol) was added drop wise at 0 °C over 10 min, after addition, the whole mixture was stirred at 25 °C.

After 2 hrs, the reaction mixture was quenched with 1 mL MeOH and then evaporated to dryness under reduced pressure. Purification by silica gel chromatography [dichloromethane:methanol (20:1 to 15:1)], provided 49 as a white solid (0.3 g, crude). LC-MS (M+H) = 657 Synthesis of compound (S)-neopentyl 2-((((2R,3S,4R,5R)(4-aminooxopyrim idin- 1(2H)-yl)(difluoromethyl)-3,4-dihydroxy-tetrahydrofuran yl)methoxy)(phenoxy)phosphorylamino)propanoate (50) A solution of compound 49 (0.3 g, crude) in HCOOH (80%, v/v, 30 mL) was stirred at room temperature. After 12 h the reaction mixture was cooled to 0 °C and neutralized with 1M aqueous NaHCO3 solution. The organic phase was extracted with ethyl acetate, washed with water, brine solution, dried (Na2SO4) and evaporated to dryness under reduced pressure.

Purification by prep-HPLC provided 50 (17 mg, 9.8%) as a white solid. LC-MS (M+H) = 590.9 H NMR (300MHz, DMSO-d ) δ 7.54–7.18 (m, 8 H), 6.32–6.06 (m, 3 H), 5.81–5.65 (m, 2 H), .48–5.46 (m, 1 H), 4.24–4.12 (m, 4 H), 3.95–3.89 (dd, 1 H), 3.79–3.69 (m, 2 H), 1.29–1.24 (m, 3 H), 0.88 (s, 9 H).

Biological Examples Influenza Assay This assay measures the ability of the active compounds derived from the compounds of formula I to inhibit the essential influenza RNA polymerase. The influenza polymerase was obtained from purified influenza virus particles and the rate of nucleotide incorporation was measured from the quantitation of a radiolabeled nucleotide tracer during the polymerase reaction.

Metabolism Assay This assay measures the ability of human cells to generate the active compounds from the compounds of formula I. The active compounds are the triphosphate (TP) derivatives of the nucleoside analogs. The assay is determining the concentration of specific nucleoside triphosphates formed in human cells exposed to compounds of formula I after methanol extraction of cells and analysis of soluble nucleoside triphosphate using LC-MS.

Table 2. Activity of nucleotide triphosphates in influenza polymerase assay.

Activity Compound Structure Number IC50 M TPP-1 B Table 2. Activity of nucleotide triphosphates in influenza polymerase assay.

Activity Compound Structure Number IC50 M TPP-2 B TPP-3 B TPP-4 A TPP-5 B TPP-6 A TPP-7 C TPP-8 A Table 2. Activity of nucleotide triphosphates in influenza polymerase assay.

Activity Compound Structure Number IC50 M TPP-9 A TPP-10 A Activity in influenza polymerase assay is as follows: A = IC < 10 M; B = IC 10-100 M; C 50 50 = IC >100 M Dosage and Administration As shown in above Table the compounds of formula I have the potential to be efficacious as antiviral drugs for the treatment of influenza infections in humans, or are metabolized to a compound that exhibit such activity.

In another embodiment of the invention, the active compound or its prodrug derivative or salt can be administered in combination with another antiviral agent, such as an anti-influenza agent or an immunomodulatory compound, including those of formula I. When the active compound or its derivative or salt are administered in combination with another antiviral or immunomodulatory agent the activity may be increased over the parent compound. This can easily be assessed by preparing the derivative and testing its anti-influenza activity according to the method described herein.

Administration of the active compound may range from continuous (intravenous drip) to several or single administrations per day (for example, Q.I.D) or less frequent administrations and may include oral, topical parenteral, intramuscular, intravenous, subcutaneous, transdermal (which may include a penetration enhancement agent), buccal and suppository administration, among other routes of administration.

The 4'-difluoromethyl substituted nucleoside derivatives as well as their pharmaceutically useable salts, can be used as medicaments in the form of any pharmaceutical formulation. The pharmaceutical formulation can be administered enterally, either orally, e.g. in the form of tablets, coated tablets, dragées, hard and soft gelatine capsules, solutions, emulsions, syrups, or suspensions, or rectally, e.g. in the form of suppositories. They can also be administered parenterally (intramuscularly, intravenously, subcutaneously or intrasternal injection or infusion techniques), e.g. in the form of injection solutions, nasally, e.g. in the form of nasal sprays, or inhalation spray, topically and so forth.

For the manufacture of pharmaceutical preparations, the 4'-substituted nucleoside derivatives, as well as their pharmaceutically useable salts, can be formulated with a therapeutically inert, inorganic or organic excipient for the production of tablets, coated tablets, dragées, hard and soft gelatine capsules, solutions, emulsions or suspensions.

The compounds of formula I can be formulated in admixture with a pharmaceutically acceptable carrier. For example, the compounds of the present invention can be administered orally as pharmacologically acceptable salts. Because the compounds of the present invention are mostly water soluble, they can be administered intravenously in physiological saline solution (e.g., buffered to a pH of about 7.2 to 7.5). Conventional buffers such as phosphates, bicarbonates or citrates can be used for this purpose. Of course, one of ordinary skill in the art may modify the formulations within the teachings of the specification to provide numerous formulations for a particular route of administration without rendering the compositions of the present invention unstable or compromising their therapeutic activity. In particular, the modification of the present compounds to render them more soluble in water or other vehicle, for example, may be easily accomplished by minor modifications (salt formulation, esterification, etc.) which are well within the ordinary skill in the art. It is also well within the ordinary skill of the art to modify the route of administration and dosage regimen of a particular compound in order to manage the pharmacokinetics of the present compounds for maximum beneficial effect in patients.

For parenteral formulations, the carrier will usually comprise sterile water or aqueous sodium chloride solution, though other ingredients including those which aid dispersion may be included. Of course, where sterile water is to be used and maintained as sterile, the compositions and carriers must also be sterilized. Injectable suspensions may also be prepared, in which case appropriate liquid carriers, suspending agents and the like may be employed.

Suitable excipients for tablets, coated tablets, dragées, and hard gelatin capsules are, for example, lactose, corn starch and derivatives thereof, talc, and stearic acid or its salts.

If desired, the tablets or capsules may be enteric-coated or sustained release by standard techniques.

Suitable excipients for soft gelatine capsules are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols.

Suitable excipients for injection solutions are, for example, water, saline, alcohols, polyols, glycerin or vegetable oils.

Suitable excipients for suppositories are, for example, natural and hardened oils, waxes, fats, semi-liquid or liquid polyols.

Suitable excipients for solutions and syrups for enteral use are, for example, water, polyols, saccharose, invert sugar and glucose.

The pharmaceutical preparations of the present invention may also be provided as sustained release formulations or other appropriate formulations.

The pharmaceutical preparations can also contain preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavourants, salts for adjustment of the osmotic pressure, buffers, masking agents or antioxidants.

The pharmaceutical preparations may also contain other therapeutically active agents known in the art.

The dosage can vary within wide limits and will, of course, be adjusted to the individual requirements in each particular case. For oral administration, a daily dosage of between about 0.01 and about 100 mg/kg body weight per day should be appropriate in monotherapy and/or in combination therapy. A preferred daily dosage is between about 0.1 and about 500 mg/kg body weight, more preferred 0.1 and about 100 mg/kg body weight and most preferred 1.0 and about 100 mg/kg body weight per day. A typical preparation will contain from about 5% to about 95% active compound (w/w). The daily dosage can be administered as a single dosage or in divided dosages, typically between 1 and 5 dosages per day.

In certain pharmaceutical dosage forms, the pro-drug form of the compounds, especially including acylated (acetylated or other) derivatives, pyridine esters and various salt forms of the present compounds are preferred. One of ordinary skill in the art will recognize how to readily modify the present compounds to pro-drug forms to facilitate delivery of active compounds to a target site within the host organism or patient. One of ordinary skill in the art will also take advantage of favorable pharmacokinetic parameters of the pro-drug forms, where applicable, in delivering the present compounds to targeted site within the host organism or patient to maximize the intended effect of the compound.

Indications and Method of Treatment Described is a method for treating a Influenza infection comprising administering to a patient in need thereof a therapeutically effective amount of a compound of Formula I.

Described is the above method, further comprising administering an immune system modulator or one or more antiviral agents that inhibits replication of Influenza, or a combination thereof.

Described is the above method for inhibiting replication of Influenza in a cell comprising administering a compound of Formula I.

Combination Therapy The compounds of the invention and their isomeric forms and pharmaceutically acceptable salts thereof are useful in treating and preventing influenza infection alone or when used in combination with other compounds targeting viral or cellular elements or functions involved in the influenza lifecycle. Classes of compounds useful in the invention include, without limitation, all classes of influenza antivirals.

The present invention is not limited to the aforementioned classes or compounds and contemplates known and new compounds and combinations of biologically active agents. It is intended that combination therapies of the present invention include any chemically compatible combination of a compound of this inventive group with other compounds of the inventive group or other compounds outside of the inventive group, as long as the combination does not eliminate the anti-viral activity of the compound of this inventive group or the anti-viral activity of the pharmaceutical composition itself.

Combination therapy can be sequential, that is treatment with one agent first and then a second agent (for example, where each treatment comprises a different compound of the invention or where one treatment comprises a compound of the invention and the other comprises one or more biologically active agents) or it can be treatment with both agents at the same time (concurrently). Sequential therapy can include a reasonable time after the completion of the first therapy before beginning the second therapy. Treatment with both agents at the same time can be in the same daily dose or in separate doses. Combination therapy need not be limited to two agents and may include three or more agents. The dosages for both concurrent and sequential combination therapy will depend on absorption, distribution, metabolism and excretion rates of the components of the combination therapy as well as other factors known to one of skill in the art. Dosage values will also vary with the severity of the condition to be alleviated. It is to be further understood that for any particular subject, specific dosage regimens and schedules may be adjusted over time according to the individual's need and the judgment of the one skilled in the art administering or supervising the administration of the combination therapy.

It will be understood that references herein to treatment extend to prophylaxis as well as to the treatment of existing conditions, and that the treatment of animals includes the treatment of humans as well as other mammals. Furthermore, treatment of an Influenza infection, as used herein, also includes treatment or prophylaxis of a disease or a condition associated with or mediated by Influenza infection, or the clinical symptoms thereof.

The features disclosed in the foregoing description, or the following claims, or the accompanying drawings, expressed in their specific forms or in terms of a means for performing the disclosed function, or a method or process for attaining the disclosed result, as appropriate, may, separately, or in any combination of such features, be utilised for realising the invention in diverse forms thereof.

The foregoing invention has been described in some detail by way of illustration and example, for purposes of clarity and understanding. It will be obvious to one of skill in the art that changes and modifications may be practiced within the scope of the appended claims.

Therefore, it is to be understood that the above description is intended to be illustrative and not restrictive. The scope of the invention should, therefore, be determined not with reference to the above description, but should instead be determined with reference to the following appended claims, along with the full scope of equivalents to which such claims are entitled.

All patents, patent applications and publications cited in this application are hereby incorporated by reference in their entirety for all purposes to the same extent as if each individual patent, patent application or publication were so individually denoted.

In this specification where reference has been made to patent specifications, other external documents, or other sources of information, this is generally for the purpose of providing a context for discussing the features of the invention. Unless specifically stated otherwise, reference to such external documents is not to be construed as an admission that such documents, or such sources of information, in any jurisdiction, are prior art, or form part of the common general knowledge in the art.

In the description in this specification reference may be made to subject matter that is not within the scope of the claims of the current application. That subject matter should be readily identifiable by a person skilled in the art and may assist in putting into practice the invention as defined in the claims of this application.

The term "comprising" as used in this specification means "consisting at least in part of". When interpreting each statement in this specification that includes the term "comprising", features other than that or those prefaced by the term may also be present. Related terms such as "comprise" and "comprises" are to be interpreted in the same manner.

WE

Claims (35)

CLAIM 1.:

1. A compound of Formula I Base wherein: Y is H or P(=X)(R’)(R); 1 1’ R is O-R or NHR ; 1’ 2a 2b 3 R is -C(R )(R )C(=O)OR ; 4 2a 2b 3 3 R’ is N(R )C(R )(R )C(=O)OR , –OP(=O)(OH)OP(=O)(OH)OH, or –OR ; R 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, 1a 1a 1b 1c 1c halo, lower haloalkyl, -N(R ) , acylamino, -SO N(R ) , -C(=O)R , -SO (R ), -NHSO (R ), 2 2 2 2 2 nitro, cyano, or R ; each R is independently H or lower alkyl; 1b 1a 1a each R is independently -OR or -N(R ) ; each R is lower alkyl; 2a 2b 1a each R and R is independently H, lower alkyl, -(CH ) N(R ) , lower 2 r 2 hydroxyalkyl, -CH SH, -(CH )S(O) Me, -(CH ) NHC(=NH)NH , (1H-indolyl)methyl, (1H- 2 2 p 2 n 2 indolyl)methyl, -(CH2) C(=O)R , 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; 2a 2b 4 or R is H and R and R together form (CH ) ; each R is independently H, lower alkyl, lower haloalkyl, phenyl or phenyl lower alkyl, wherein phenyl and phenyl lower alkyl are optionally substituted with lower alkoxy; 3 1’’ or R and R together form CH ; each R is independently H, lower alkyl; 2b 4 or R and R together form (CH ) ; w y z R , R , and R are each independently H, OH or F; R is H, OH, or F; or R and R together form a bond; or R and R together form a bond; X is O or S; Base is uracil, cytosine, guanine, adenine, or thymine, each of which may optionally be substituted with one or more hydroxy, lower alkyl, lower alkoxy, halo, nitro or cyano; w y z x with the proviso that if R is H, R is H, and R is H, then R is not H; or a pharmacologically acceptable salt thereof. W y x z

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

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

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

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

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

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

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

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

10. The compound of claim 1, wherein R is H, R is H, R is OH, and R is F. 3 3 1 1

11. The compound of claim 1, wherein R’ is O-R , R is lower alkyl, R is –OR , and R and R together form a bond. 1 1 1’’

12. The compound of claim 1, wherein R is –OR , R is phenyl substituted with R , R’ is – 3 3 1’’ OR , and R and R together form CH2.

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

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

15. The compound of claim 1, wherein R is O-R , and R is phenyl optionally substituted with methoxy.

16. The compound of claim 1, wherein R is O-R , and R is naphthylenyl. 4 2a 2b 3 4 2a

17. The compound of claim 1, wherein R’ is N(R )C(R )(R )C(=O)OR , R is H, R is H, 2b 3 R is methyl, and R is isopropyl.

18. The compound of claim 1, wherein R’ is -OP(=O)(OH)OP(=O)(OH)OH.

19. The compound of claim 1, wherein Base is cytidine optionally substituted with halo.

20. The compound of claim 1, wherein Base is uridine optionally substituted with halo.

21. The compound of claim 1, wherein Base is guanosine.

22. The compound of claim 1, wherein Base is adenosine.

23. A compound selected from the list consisting of: 4’-Difluoromethyluridine; 4’-Difluoromethyluridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyluridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyluridine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate}; 4’-Difluoromethyluridine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate}; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-uridine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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’-Difluoromethylfluorouridine; 4’-Difluoromethylfluorouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluorouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluorouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluorouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluorouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluorouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyluridine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate}; 4’-Difluoromethyl5-fluorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate}; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)fluorouridine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)fluorouridine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] fluorouridine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] fluorouridine; 4’-Difluoromethylfluorouridine-3’,5’-cyclic phosphoric acid isopropyl ester; 4’-Difluoromethylfluorouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 4’-Difluoromethylchlorouridine; 4’-Difluoromethylchlorouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylchlorouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylchlorouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylchlorouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylchlorouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylchlorouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylchlorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate}; 4’-Difluoromethylchlorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate}; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)chlorouridine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)chlorouridine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl]chlorouridine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]chlorouridine; 4’-Difluoromethylchlorouridine-3’,5’-cyclic phosphoric acid isopropyl ester; 4’-Difluoromethylchlorouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 4’-Difluoromethylcytidine; 4’-Difluoromethylcytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylcytidine-5’-(O-phenyl-N-(S)(benzyloxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylcytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylcytidine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate}; 4’-Difluoromethylcytidine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate}; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-cytidine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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’-Difluoromethylfluorocytidine; 4’-Difluoromethylfluorocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluorocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate}; 4’-Difluoromethylfluorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate}; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)fluorocytidine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)fluorocytidine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] fluorocytidine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] fluorocytidine; 4’-Difluoromethylfluorcytidine-3’,5’-cyclic phosphoric acid isopropyl ester; 4’-Difluoromethylfluorocytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 4’-Difluoromethylchlorocytidine; 4’-Difluoromethylchlorocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylchlorocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyl5-chlorocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylchlorocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylchlorocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylchlorocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylchlorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate}; 4’-Difluoromethylchlorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate}; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)chlorocytidine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)chlorocytidine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] chlorocytidine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] chlorocytidine; 4’-Difluoromethylchlorocytidine-3’,5’-cyclic phosphoric acid isopropyl ester; 4’-Difluoromethylchlorocytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 4’-Difluoromethyladenosine; 4’-Difluoromethyladenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyladenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyladenosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethyladenosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-adenosine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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’-Difluoromethyladenosine; 4’-Difluoromethyladenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyladenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethyladenosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethyladenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)adenosine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)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’-Difluoromethylguanosine; 4’-Difluoromethylguanosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylguanosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylguanosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylguanosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-guanosine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyluridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-uridine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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’-difluoromethylfluorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl) fluorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) fluorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl]fluorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]uridine; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-3’,5’-cyclic phosphoric acid isopropyl ester; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl) chlorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) chlorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl]chlorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]chlorouridine; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-3’,5’-cyclic phosphoric acid isopropyl ester; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- cytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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’-difluoromethylfluorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl) fluorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) fluorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl]fluorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]cytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-3’,5’-cyclic phosphoric acid isopropyl ester; 2’-Deoxy-2’-fluoro-4’-difluoromethylfluorocytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl) chlorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) chlorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl]chlorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] chlorocytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-3’,5’-cyclic phosphoric acid isopropyl ester; 2’-Deoxy-2’-fluoro-4’-difluoromethylchlorocytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyladenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- adenosine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyguanosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- guanosine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyarauridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- arauridine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylarauridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- arauridine; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorin yl)-arauridine; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorin 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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethlaracytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- aracytidine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylaracytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- aracytidine; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorin yl)-aracytidine; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorin 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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethlaraadenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraadenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraadenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraadenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraadenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate 2’-Deoxy-2’-fluoro-4’-difluoromethylaraadenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraadenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- araadenosine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethlaraguanosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethylaraguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- araguanosine; 2’-Deoxy-2’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyluridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- uridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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’-difluoromethylfluorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Dideoxy-2’-difluoro-4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl) fluorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) fluorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] fluorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]uridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-3’,5’-cyclic phosphoric acid isopropyl ester; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl) chlorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) chlorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] chlorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] chlorouridine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-3’,5’-cyclic phosphoric acid isopropyl ester; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylchlorouridine-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)(isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylcytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- cytidine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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’-difluoromethylfluorocytidine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl) fluoroucytidine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) fluorocytidine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] fluorocytidine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]cytidine; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-3’,5’-cyclic phosphoric acid isopropyl ester; 2’-Deoxy-2’,2’-difluoro -4’-difluoromethylfluorocytidine-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) (isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethylcytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-2’-deoxy-2,2’’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 5-Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 5-Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorin- 2-yl) cytidine; 5-Chloro-2’-deoxy-2’,2’-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2- benzodioxaphosphorinyl) 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) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyladenosine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyladenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyladenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- adenosine; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-O-(2-oxidoH-1,3,2- benzodioxaphosphorinyl)-cytidine; 2’-Deoxy-2’,2’-difluoro-4’-difluoromethylguanosine-5’-O-(2-sulfideH-1,3,2- benzodioxaphosphorinyl)-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)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethlarauridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylarauridine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate}; 4’-Difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate}; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-arauridine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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’-Difluoromethylfluoroarauridine; 4’-Difluoromethylfluoroarauridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroarauridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate 4’-Difluoromethylfluoroarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate 4’-Difluoromethylfluoroarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate 4’-difluoromethylfluoroarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylfluoroarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)fluoroarauridine; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) fluoroarauridine; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] fluoroarauridine; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] fluoroarauridine; 4’-Difluoromethyl—5-fluoroarauridine-3’,5’-cyclic phosphoric acid isopropyl ester; 4’-Difluoromethylfluoroarauridine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 5-Chloro-4’-difluoromethylarauridine; 5-Chloro-4’-difluoromethylarauridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-4’-difluoromethylarauridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-4’-difluoromethylarauridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-4’-difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 5-Chloro -4’-difluoromethylarauridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 5-Chloro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-arauridine; 5-Chloro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethlaracytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaracytidine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-aracytidine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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’-Difluoromethylfluoroaracytidine; 4’-Difluoromethylfluoroaracytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroaracytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-difluoromethylfluoroaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylfluoroaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)fluoroaracytidine; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl) fluoroaracytidine; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] fluoroaracytidine; 2’-Deoxy-2’,5-difluoro-4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] fluoroaracytidine; 4’-Difluoromethyl—5-fluoroaracytidine-3’,5’-cyclic phosphoric acid isopropyl ester; 4’-Difluoromethylfluoroaracytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 5-Chloro-4’-difluoromethylaracytidine; 5-Chloro-4’-difluoromethylaracytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-4’-difluoromethylaracytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4-Chloro-2’-deoxy-2’-fluoro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-4’-difluoromethylaracytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-4’-difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 5-Chloro -4’-difluoromethylaracytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 5-Chloro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-aracytidine; 5-Chloro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethlaraadenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaraadenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylaraadenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaraadenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylaraadenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaraadenosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylaraadenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-araadenosine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethlaraadenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaraguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylaraguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaraguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylaraguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylaraguanosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylaraguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-araguanosine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyluridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-uridine; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylcytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- cytidine; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- xylouridine; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- xylouridine; 3’-Deoxy-3’,5-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorin yl)-xylouridine; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorin 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)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- xylocytidine; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethylxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’,5-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- xylocytidine; 3’-Deoxy-3’,5-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethylxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 5-Chloro-3’-deoxy -3’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorin yl)-xylocytidine; 5-Chloro-3’-deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorin 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) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloadenosine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloadenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloadenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloadenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloadenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloadenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloadenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- xyloadenosine; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloguanosine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethylxyloguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- xyloguanosine; 3’-Deoxy-3’-fluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxylouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxylouridine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-xylouridine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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’-Difluoromethylfluoroxylouridine; 4’-Difluoromethylfluoroxylouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluororxylouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylfluororxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)fluoroxylouridine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)fluoroxylouridine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl]fluoroxylouridine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]fluororxylouridine; 4’-Difluoromethylfluoroxylouridine-3’,5’-cyclic phosphoric acid isopropyl ester; 4’-Difluoromethylfluoroxylouridine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 5-Chloro-4’-difluoromethylxylouridine; 5-Chloro-4’-difluoromethylxylouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-4’-difluoromethylxylouridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-4’-difluoromethylxylouridine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-4’-difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 5-Chloro-4’-difluoromethylxylouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 5-Chloro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-xylouridine; 5-Chloro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxylocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxylocytidine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylxylocytidine-5’-{N,N’-bis[(S) (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’-Difluoromethylfluoroxylocytidine; 4’-Difluoromethylfluoroxylocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluororxylocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylfluoroxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylfluoroxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylfluororxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 4’-Difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)fluoroxylocytidine; 4’-Difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)fluoroxylocytidine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl]fluoroxylocytidine; 4’-Difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl]fluororxylocytidine; 4’-Difluoromethylfluoroxylouridine-3’,5’-cyclic phosphoric acid isopropyl ester; 4’-Difluoromethylfluoroxylocytidine-3’,5’-cyclic thiophosphoric acid isopropyl ester; 5-Chloro-4’-difluoromethylxylocytidine; 5-Chloro-4’-difluoromethylxylocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-4’-difluoromethylxylocytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-4’-difluoromethylxylocytidine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-4’-difluoromethylxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 5-Chloro-4’-difluoromethylxylocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 5-Chloro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)-xylocytidine; 5-Chloro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)-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)(isopropoxycarbonyl)ethyl; phosphoramidate; 4’-Difluoromethylxyloadenosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxyloadenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxyloadenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxyloadenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxyloadenosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxyloadenosine-5’-{N,N’-bis[(S)(isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylxyloadenosine-5’-{N,N’-bis[(S) (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)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxyloguanosine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxyloguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxyloguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxyloguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl phosphoramidate; 4’-Difluoromethylxyloguanosine-5’-(Onaphthyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 4’-Difluoromethylxyloguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 4’-Difluoromethylxyloguanosine-5’-{N,N’-bis[(S) (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)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyluridine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- uridine; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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’-difluoromethylfluorouridine; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorouridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorouridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluororuridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluororuridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorouridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorouridine-5’-O-(2-oxidoH-1,3,2- benzodioxaphosphorinyl)-uridine; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorouridine-5’-O-(2-sulfideH-1,3,2- benzodioxaphosphorinyl)-uridine; 3’-Deoxy-3’,3’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] fluorouridine; 3’-Deoxy-3’,3’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] fluorouridine; 5-Chloro-3’-deoxy-3’,3’-difluoro-4’-difluoromethyluridine; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-O-(2-oxidoH-1,3,2- benzodioxaphosphorinyl)-uridine; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethyluridine-5’-O-(2-sulfideH-1,3,2- benzodioxaphosphorinyl)-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)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylcytidine-5’-(O-phenyl-N-(S)(isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- cytidine; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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’-difluoromethylfluorocytidine; 3’-Deoxy-3’.3’-difluoro-4’-difluoromethylfluorocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorocytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorocytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluororcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluororcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylfluorocytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- 5- fluorocytidine; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethy -5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 5- fluorocytidine; 3’-Deoxy-3’,3’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)phosphinyl] fluorocytidine; 3’-Deoxy-3’,3’-difluoro -4’-difluoromethyl-5’-O-[bis(4-methoxyphenoxy)thiophosphinyl] fluorocytidine; 5-Chloro-3’-deoxy-3’,3’-difluoro-4’-difluoromethylcytidine; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-O-(2-oxidoH-1,3,2- benzodioxaphosphorinyl)-uridine; 5-Chloro-3’-deoxy -3’,3’-difluoro-4’-difluoromethylcytidine-5’-O-(2-sulfideH-1,3,2- benzodioxaphosphorinyl)-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)(isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyladenosine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyladenosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyladenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyladenosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- adenosine; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylguanosine-5’-(O-phenyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl phosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylguanosine-5’-(Onaphthyl-N-(S) (isopropoxycarbonyl)ethyl thiophosphoramidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]phosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethylguanosine-5’-{N,N’-bis[(S) (isopropoxylcarbonyl)ethyl]thiophosphorodiamidate; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-oxidoH-1,3,2-benzodioxaphosphorinyl)- guanosine; 3’-Deoxy-3’,3’-difluoro-4’-difluoromethyl-5’-O-(2-sulfideH-1,3,2-benzodioxaphosphorinyl)- 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.

24. A compound according to any one of claims 1 to 23 for use as a therapeutically active substance.

25. A pharmaceutical composition comprising a compound in accordance with any one of claims 1 to 23 and a therapeutically inert carrier.

26. The pharmaceutical composition of claim 25, in combination with one or more antiviral compounds.

27. The pharmaceutical composition of claim 26, wherein the one or more antiviral compounds comprises one or more anti-Influenza compounds.

28. A compound according to any one of claims 1 to 23 for use in the treatment or prophylaxis of Influenza infection.

29. A pharmaceutical composition according to any one of claims 25 to 27 for use in the treatment or prophylaxis of Influenza infection.

30. Use of a compound according to any one of claims 1 to 23 in the manufacture of a medicament for the treatment or prophylaxis of Influenza infection.

31. A compound of formula I or a pharmacologically acceptable salt thereof as claimed in any one of claims 1 to 23, substantially as herein described with reference to any example thereof.

32. A compound of formula I or a pharmacologically acceptable salt thereof for use as claimed in claim 24 or claim 28, substantially as herein described with reference to any example thereof.

33. A pharmaceutical composition as claimed in any one of claims 25 to 28, substantially as herein described with reference to any example thereof.

34. A pharmaceutical composition for use as claimed in claim 29, substantially as herein described with reference to any example thereof.

35. Use as claimed in claim 30, substantially as herein described with reference to any example thereof.