DIFLUORONUCLEOSIDE PHOSPHONIC ACIDS AND DERIVATIVES THEREOF

Abstract: Difluoronucleoside phosphonic acids and derivatives thereof of formula (II) where R is base selected from the group consisting of: (i), (ii), (iii), (iv), and (v) wherein R<1> is hydrogen, methyl, bromo, fluoro, chloro or iodo; R<2> is hydroxy or -NR<4>R<5>, where R<4> and R<5> are independently selected from the group consisting of hydrogen, methyl, ethyl and propyl; R<3> is hydrogen, bromo, chloro or iodo; both R<6> are the same, and are either -OR<7> or -(O<->R<8>), where R<7> is selected from the group consisting of hydrogen, methyl, ethyl, and isopropyl; R<8> is a pharmaceutically acceptable cation; and pharmaceutically acceptable salts and solvates thereof; are described and claimed as antiviral and antineoplastic agents.

Description: TITLE DIFLUORONUCLEOSIDE PHOSPHONIC ACIDS AND DERIVATIVES THEREOF The invention relates to the art of organic chemistry. Specifically it relates to difluoronucleosides that have utility in certain pharmaceutical applications. Certain difluoronucleosides have been found to have utility as anti-viral compounds (U.S. Patent No. 4,808,614) and as anti-neoplastic compounds (U.S. Patent No 5,464,826). A difluoronucleoside compound which is currently being used in the treatment of solid tumors in humans is gemcitabine hydrochloride (formula (I) ) : formula (i; It is desirable to develop additional difluro- nucleoside compounds in order to have alternative compounds to offer in the treatment of viral diseases and neoplastic diseases . This invention relates to difluoronucleoside phosphonic acids and derivatives thereof of formula (Ii; formula (II) where R is a base selected from the group consisting of ii ) ( iii ) iv ) (v) wherein: R! is hydrogen, methyl, bromo, fluoro, chloro or iodo; R^ is hydroxy or -NR^R^, where R^ and R^ are independently selected from the group consisting of hydrogen, methyl, ethyl and propyl ; R^ is hydrogen, bromo, chloro or iodo; both R^ are the same, and are either, -OR 7 or -(0 ~ R^), where R 7 is selected from the group consisting of hydrogen, methyl, ethyl, and isopropyl; R8 is a pharmaceutically acceptable cation; and pharmaceutically acceptable salts and solvates thereof. This invention also relates to halogenated difluoronucleoside compounds of formula (B) : formula (B) where X is -Cl, -Br, or -I, and R is as defined previously. This invention also relates to a method of treating susceptible neoplasms in mammals comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula (II) . This invention also relates to a method of treating Herpes viral infections in mammals comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula (II) . This invention also relates to pharmaceutical compositions comprising one or more compounds of formula (II) in combination with pharmaceutically acceptable excipients and/or diluents. The following definitions are set forth to illustrate and define the meaning and scope of the various terms used to describe the invention herein. The term "pharmaceutically acceptable cations" includes, but is not limited to, pharmaceutically acceptable alkali metal, alkaline earth metal and organic amine cations. These cations can be mono-, di- or trivalent cations. Preferred cations include, but are not limited to, sodium (Na + ) , potassium (K + ) , lithium (Li + ) , calcium (Ca ++ ) , magnesium (Mg ++ ) , aluminum (Al +++ ) , zinc (Zn ++ ), ammonium (NH 4 +) , trimethylammonium ((CH 3 )3NH + ), and triethanolammonium ( (HOCH2CH 2 ) 3 NHA . A "pharmaceutically acceptable salt" may be any non-toxic salt derived from an inorganic or organic acid that is suitable for administration as a drug. The salts are derived from inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like and organic acids such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, salicylic acid, p-toluene-sulfonic acid, hexanoic acid, heptanoic acid, cyclopentanepropionic acid, lactic acid, o- (4-hydroxy-benzoyl) benzoic acid, 1,2- ethanedisulfonic acid, 2 -hydroxyethanesulfonic acid, benzenesulfonic acid, p-chlorobenzenesulfonic acid, 2- naphthalenesulfonic acid, camphorsulfonic acid, 4- methylbicyclo [2.2.2 ] oct-2-ene-l-carboxylic acid, glucoheptonic acid, 4, 4 ' -methylenebis- (3-hydroxy-2- naphthoic) acid, 3-phenylpropionic acid, trimethylacetic acid, t-butylacetic acid, laurylsulfuric acid, glucuronic acid, glutamic acid, 3-hydroxy-2-naphthoic acid, stearic acid, muconic acid and the like. A "pharmaceutically acceptable solvate" refers to an aggregate of a compound of formula (II) with solvent molecules . The solvent may be water or any common organic solvent . The term "therapeutically effective amount" refers to a dosage sufficient to cause a positive change in the disease state being treated. The term "positive change" will vary in meaning depending on the patient, the disease and the treatment being undergone. For example, an effective amount of an oncolytic can be an amount that causes a reduction in the size of a cancerous tumor, or where no reduction in tumor size occurs, an effective amount of an oncolytic could be that amount that causes a decrease in analgesic consumption for the patient suffering from cancer . Compounds of formula (II) : formula (II! include compounds where the stereochemical orientation between the carbohydrate derivative ring and the base is in the α (alpha) configuration, as depicted in formula (Ila) : formula (Ila) in the β (beta) configuration, as depicted in formula (lib) formula (lib) and mixtures thereof; where R and R^ are as defined previously . Preferred compounds of formula (II) are those compounds where the stereochemical orientation between the carbohydrate derivative ring and the base is in the β configuration, A more preferred compound of Formula (II) is where the stereochemical orientation between the carbohydrate derivative ring and the base is in the β configuration, R is : and R^ is -(0 R^) where R^ is a pharmaceutically acceptable cation. An especially preferred compound of formula (II) is 1 ' -desoxy-1 ' -β- (lH-2-oxo-4-amino-pyrimidin-l-yl) -2 ' , 2 ' - difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate, which has the formula : Other preferred compounds of formula (II) , include, but are not limited to the following, wherein it is understood that both the α and β stereochemical orientations of the compounds are included: 1A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IB) 1 ' -desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-5-methyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; 1C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-bromo-pyrimidin-l- yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; ID) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- 1-yl) -2 ', 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IE) 1 ' -desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-5-chloro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IF) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-pyrimidin-l-yl) -2 ' , 2 ' - difluoro-5 ' -desoxy-5 ' -phosphono ribose; IG) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-methyl-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; 1H) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; II) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-fluoro-pyrimidin-1-yl) - 2 ', 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; 1J) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-chloro-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IK) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IL) 1 ' -desoxy-1 ' - (guanin-9-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' - phosphono ribose; 1M) 1 ' -desoxy-1 ' - (l-dehydro-2-desamino-6-desoxo-6- aminoguanin-9-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IN) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; 10) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-iodoethylenyl ) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IP) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-hydroxy-5- (2-chloroethylenyl ) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; 1Q) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-bromoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; 2A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-methyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-bromo-pyrimidin-l- yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2D) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- 1-yl) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2E) 1 ' -desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-5-chloro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2F) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-pyrimidin-l-yl) -2 ' , 2 ' - difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2G) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-methyl-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2H) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-l-yl) - 2 ' , 2 ' -difluo-5 ' -desoxyribose 5 ' -dimethylphosphonate; 21) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-fluoro-pyrimidin-1-yl) - 2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2J) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5-chloro-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2K) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2L) 1 ' -desoxy-1 ' - (guanin-9-yl) -2 ' , 2 ' -difluoro-5 ' - desoxyribose 5 ' -dimethylphosphonate; 2M) 1 ' -desoxy-1 ' - (l-dehydro-2-desamino-6-desoxo-6- aminoguanin-9-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - dimethylphosphonate ; 2N) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 20) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-iodoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - dimethylphosphonate ; 2P) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-chloroethyleny.f) - pyrimidin-1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - dimethylphosphonate; 2Q) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-bromoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - dimethylphosphonate; 3A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-methyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-bromo-pyrimidin-l- yl) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3D) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3E) 1 ' -desoxy-1 '-(1,3 -dihydro-2 , 4-dioxo-5-chloro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3F) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-pyrimidin-l-yl) -2 ' , 2 ' - difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3G) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5-methyl-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3H) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-l-yl ) - 2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 31) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-fluoro-pyrimidin-1-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3J ) 1 ' -desoxy-1 ' - ( lH-2 -oxo-4 -amino- 5 -chloro-pyrimidin-l -yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3K) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3L) 1 ' -desoxy-1 ' - (guanin-9-yl ) -2 ' ,2 ' -difluoro-5 ' - desoxyribose 5 ' -diethylphosphonate; 3M) 1 ' -desoxy-1 ' - ( l-dehydro-2-desamino-6-desoxo-6- aminoguanin-9-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diethylphosphonate; 3N) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 30) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-iodoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diethylphosphonate ; 3P) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-chloroethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diethylphosphonate ; 3Q) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-bromoethylenyl) - pyrimidin-1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diethylphosphonate; 4A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-5-methyl-pyrimidin- 1-yl) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-5-bromo-pyrimidin-l- yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4D) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4E) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-chloro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropyl- phosphonate; 4F) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-pyrimidin-l-yl) -2 ' , 2 ' - difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4G) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5-methyl-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4H) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 41) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5-fluoro-pyrimidin-1-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4J) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-chloro-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate ; 4K) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl) - 2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4L) 1 ' -desoxy-1 ' - (guanin-9-yl ) -2 ' , 2 ' -difluoro-5 ' - desoxyribose 5 ' -diisopropylphosphonate; 4M) 1 ' -desoxy-1 ' - (l-dehydro-2-desamino-6-desoxo-6- aminoguanin-9-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diisopropylphosphonate; 4N) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 40) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-iodoethylenyl) - pyrimidin-1-yl) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5'- diisopropylphosphonate; 4P) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-chloroethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diisopropylphosphonate; 4Q) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-hydroxy-5- (2-bromoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diisopropylphosphonate; pharmaceutically acceptable salts; pharmaceutically acceptable solvates; and mixtures thereof. Other preferred compounds, include, but are not limited to the following, wherein it is understood that both the α and β stereochemical orientations of the compounds are included: 5A) 1 ' -desoxy-1 ' - ( 1 , 3 -dihydro-2 , 4 -dioxo-pyrimidin-l -yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate; 5B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-methyl-pyrimidin- 1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diammoniumphosphonate; 5C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-bromo-pyrimidin-l- yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate; 5D) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diammoniumphosphonate; 5E) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-chloro-pyrimidin- 1-yl) -2 ' ,2 ' -difluoro-5 ' -desoxyribose 5 ' - diammoniumphosphonate ; 5F) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-pyrimidin-l-yl) -2 ' , 2 ' - difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate; 5G) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-methyl-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate; 5H) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate; 51) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-fluoro-pyrimidin-1-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate; 5J) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-chloro-pyrimidin-l-yl) - 2 ' ,2 ' -difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate; 5k) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl) - 2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate; 5L) 1 ' -desoxy-1 ' - (guanin-9-yl) -2 ' ,2 ' -difluoro-5 ' - desoxyribose 5 ' -diammoniumphosphonate; 5M) 1 ' -desoxy-1 ' - (l-dehydro-2-desamino-6-desoxo-6- aminoguanin-9-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diammoniumphosphonate; 5N) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diammoniumphosphonate ; 50) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-iodoethylenyl) - pyrimidin-1-yl) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5'- diammoniumphosphonate ; 5P) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-chloroethylenyl) - pyrimidin-1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diammoniumphosphonate ; 5Q) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-bromoethylenyl ) - pyrimidin-1-yl) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5'- diammoniumphosphonate; 6A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-5-methyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-bromo-pyrimidin-l- yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6D) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- 1-yl) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6E) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-chloro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6F) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-pyrimidin-l-yl) -2 ' , 2 ' - difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6G) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-methyl-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6H) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 61) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-fluoro-pyrimidin-1-yl ) - 2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6J) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-chloro-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6K) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6L) 1 ' -desoxy-1 '- (guanin-9-yl) -2 ' ,2 ' -difluoro-5 ' - desoxyribose 5 ' -disodiumphosphonate; 6M) 1 ' -desoxy-1 ' - (l-dehydro-2-desamino-6-desoxo-6- aminoguanin-9-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - disodiumphosphonate ; 6N) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 60) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-iodoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - disodiumphosphonate ; 6P) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-chloroethylenyl) - pyrimidin-1-yl) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5'- disodiumphosphonate; 6Q) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-bromoethylenyl) -pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' - desoxyribose 5 ' -disodiumphosphonate; pharmaceutically acceptable solvates; and mixtures thereof. Compounds of formula (B) include, but are not limited to the following, wherein it is understood that both the α and β stereochemical orientations of the compounds are included: 7A) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-pyrimidin-l-yl) -2 ' , 2 ' - difluoro-5 ' -desoxy-5 ' -bromoribose; 7B) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-pyrimidin-l-yl) -2 ' , 2 ' - difluoro-5 ' -desoxy-5 ' -chlororibose; 7C) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-pyrimidin-l-yl) -2 ' , 2 ' - difluoro-5 ' -desoxy-5 ' -iodoribose; 8A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 8B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 8C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 9A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-methyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 9B) 1 ' -desoxy-1 '-(1,3 -dihydro-2 , 4-dioxo-5-methyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 9C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-5-methyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 10A) 1 ' -desoxy-1 ' - (guanin-9-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' - bromoribose; 10B) 1 ' -desoxy-1 ' - (guanin-9-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' - chlororibose; IOC ) 1 ' -desoxy-1 ' - (guanin-9-yl) -2 ' ,2 ' -difluoro-5 ' -desoxy-5 ' - iodoribose; 11A) 1 ' -desoxy-1 ' - ( l-dehydro-2-desamino-6-desoxo-β-amino- guanin-9-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 11B) 1 ' -desoxy-1 ' - (l-dehydro-2-desamino-6-desoxo-6-amino- guanin-9-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 11C) 1 ' -desoxy-1 ' - (l-dehydro-2-desamino-6-desoxo-6-amino- guanin-9-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 12A) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 12B) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 12C) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 13A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-bromo-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 13B) 1 ' -desoxy-1 ' - ( 1 , 3-dihydro-2 , 4-dioxo-5-bromo-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 13C) 1 ' -desoxy-1 ' - (1 , 3-dihydro-2 , 4-dioxo-5-bromo-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy- ' -iodoribose; 14A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 14B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 14C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-fluoro-pyri idin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 15A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-chloro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 15B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-chloro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 15C) 1 '-desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-5-chloro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 16A) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 16B) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 16C) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 17A) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-fluoro-pyrimidin-1- yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 17B) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-fluoro-pyrimidin-1- yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose ; 17C) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-fluoro~pyrimidin-l- yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 18A) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5-chloro-pyrimidin-l- yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 18B) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-chloro-pyrimidin-l- yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 18C) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5-chloro-pyrimidin-l- yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 19A) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 19B) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 19C) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 20A) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-iodoethylenyl ) - pyrimidin-1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 20B) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5- (2-iodoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 20C) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5- (2-iodoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 21A) 1' -desoxy-1 '- ( lH-2-oxo-4-hydroxy-5- (2-chloroethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 21B) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5- (2-chloroethylenyl ) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 21C) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5- (2-chloroethylenyl ) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 22A) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-bromoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 22B) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5- (2-bromoethylenyl) - pyrimidin-1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 22C) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5- (2-bromoethylenyl) - pyrimidin-1-yl) -2 ', 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; and pharmaceutically acceptable salts; pharmaceutically acceptable solvates; and mixtures thereof. An especially preferred compound of formula (B) is: 1 ' -desoxy-1-β- (lH-2-oxo-4-amino-pyrimidin-l-yl) -2 ' , 2 ' - difluoro-5 ' -desoxy-5-bromoribose . The first step in the process to make the difluoronucleoside phosphonic diacid compounds and derivatives thereof of formula (II) is to substitute a -Cl, -Br or -I in place of the -OH group on the 5 ' carbon of the carbohydrate derivative ring of a difluoronucleoside compound of formula (A) . formula (A) where R is as defined previously. Compounds of formula (A) can be obtained by following the procedures described in U.S. Patent No . ' s 4,808,614 and 5,464,826, the disclosures of which are hereby incorporated by reference. Additional syntheses of certain difluoronucleosides of formula (A) are described in U.S. Patent No . * s 4,965,374, 5,223,608, 5,371,210, 5,401,838, 5,420,266, 5,426,183, 5,434,254, 5,480,992, and 5 , 606, 048 ; the disclosures of which are also hereby incorporated by reference. Some of these syntheses conclude with the difluoronucleoside still having protecting groups on certain of its hydroxy and/or amino substituents . It is understood that the herein described syntheses of the difluoronucleoside phosphonic acids and their derivatives of formula (II) require that any existing protecting groups on the -OH moieties present in the difluoronucleosides first be removed. This is necessary in order to allow the -OH moiety on the 5' carbon to be displaced in the first step of the process. It is also understood that removal of hydroxy protecting groups is a process that is well-known in the art of synthetic organic chemistry see, e.g., "Protective Groups in Organic Synthesis " , 2nd edition, T. . Greene and P.G.M. uts, © 1991 by John Wiley & Sons, Inc. In order to substitute a chloro, bromo or iodo in place of the hydroxy moiety on the 5 ' carbon of the carbohydrate derivative ring, a difluoronucleoside of formula (A) is contacted with a halogenating agent in a solvent. The halogenating agent is selected from any suitable halogenating agent such as, but not limited to, carbon tetrahalides such as carbon tetrachloride, carbon tetrabromide, and carbon tetraiodide. Additional halogenating agents include phosphorous tribromide and thionyl chloride. When a carbon tetrahalide is used, triphenylphosphine is added to the liquid carbon tetrahalide. The preferred halogen is bromine. The preferred halogenating agent is carbon tetrabromide with triphenylphosphine added. The solvent for this halogenation is selected from a group of suitable organic solvents including, but not limited to, dimethylformamide (DMF) , dimethyl acetamide (DMAc) , N-methylpyrrolidinone (NMP) , 1, 3 -dimethyl-3 , 4, 5 , 6- tetrahydro-2 (1H) -pyrimidinone (dMPU) , hexamethyl- phosphoramide (HMPA) and mixtures thereof. 1 , 3-dimethyl- 3 , 4, 5, 6-tetrahydro-2 (1H) -pyrimidinone is the preferred solvent when carbontetra bromide with triphenylphosphine is used as the brominating agent. The halogenation reaction is conducted at elevated temperatures, between at least about 40°C and at most about 75°C, preferably between about 50°C and about 70°C and most preferably about 60°C, for from at least about 30 minutes to at most about 5 hours, preferably from at least about 45 minutes to at most about 2 hours and most preferably for about 1 hour . Halogenation at the 5 ' position of unprotected nucleosides is further described in "Facile 5 ' -Halogenation of Unprotected Nucleosides", Nucl eosides & Nucleotides , 6(3) , 575-580 (1987) . The halogenated difluoronucleoside of formula (B) : formula (B) where X is -Cl, -Br, or -I, and R is as defined previously; is then isolated and purified using standard techniques known in the art, such as, but not limited to crystallization, filtration and chromatography . The purified compound of formula (B) can be used in the next step of the process. Or a compound of formula (B) can also be converted to a pharmaceutically acceptable salt or solvate, using standard techniques known in the art, and the compound, salt or solvate can be used as an antineoplastic or antiviral pharmaceutical compound. All primary and secondary amino groups and -OH groups on the halogenated compound of formula (B) must now be protected before the next step of the reaction. Accordingly, the halogenated difluoronucleoside of formula (B) is next contacted by one or more suitable protecting group reagents such that any unprotected primary and secondary amino groups and -OH groups can all be protected. It should be noted that if all the amino substituents present were already protected on the difluoronucleoside starting material of formula (A) it is only necessary to provide a protecting group for the -OH moieties at this point. It is preferred that the protecting group reagent is selected such that the primary and second amino groups and -OH groups can be protected by the same protecting group. It is preferred that there be only one protecting group reagent selected in order not to have to conduct multiple protecting group reagent addition reactions. One such suitable protecting group reagent capable of supplying a protecting group that is capable of protecting primary and second amino groups and -OH groups is an acetylating reagent. An acetylating reagent acts to protect primary and secondary amino groups and -OH groups with a -COCH3 group. Acetylating reagents can be any of those known in the art, including, but not limited to, acetyl chloride and acetic anhydride. The preferred acetylating reagent is acetic anhydride . Typically, introduction of a protecting group takes place in a suitable solvent . One such group of suitable solvents for this reaction is organic solvents such as pyridine, DMF, DMAc, NMP, dMPU, HMPA and mixtures thereof. A preferred solvent for this reaction is pyridine. The reaction to affix the protecting group is usually conducted at lowered temperatures, between about -25°C and about 10°C, preferably between about -10°C and about 8°C and most preferably between about 0°C and about 5°C; for from at least about 1 hour to at most about 30 hours, preferably from at least about 5 hours to at most about 20 hours and most preferably for about 18 hours. The protected difluoronucleoside of formula (C) : formula (C) where each Pg is individually a suitable hydroxy and amino protecting group which is (are) bonded to the -O affixed to the 3 ' carbon on the ribose ring and also bonded to any primary and secondary amino group affixed to the (R) ring, and X, R, R- 1 -^ and R^ are as defined previously; is then isolated and purified using standard techniques known in the art, such as, but not limited to those, previously listed. The next step is for the protected halogenated nucleoside of formula (C) to be contacted by a reagent capable of displacing the halogen on the number 5 carbon of the carbohydrate derivative ring with a -PO(O-R 2 0)2 moiety, where R^O is methyl, ethyl or isopropyl. Suitable phosphonating reagents include, but are not limited to trimethyl phosphite, triethyl phosphite and triisopropyl phosphite. Of these suitable phosphonating reagents, triethyl phosphite is preferred. The phosphonating reaction can be conducted using the phosphonating reagent as both a reagent and a solvent. This phosphonating reaction requires both elevated temperatures and a large amount of time. When triethyl phosphite is used as the phosphonating agent, the reaction is conducted at elevated temperatures, between at least about 100°C and about 170°C, preferably between about 125°C and about 170°C and most preferably between about 160°C and about 170°C, for from at least about 10 hours to at most about 48 hours, preferably for from at least about 20 hours to at most about 40 hours and most preferably for about 30 hours. When trimethyl phosphite is used as the phosphonating agent, the reaction is conducted at lowered temperatures (because of the lower boiling point (111-112°C) of the trimethyl phosphite) , between at least about 60°C and about 110°C, preferably between about 75°C and about 110°C and most preferably between about 100°C and about 110°C, for from at least about 20 hours to at most about 100 hours, preferably for from at least about 50 hours to at most about 100 hours and most preferably for about 60 hours. When triisopropyl phosphite is used as the phosphonating agent, the reaction is conducted ac much lower temperatures because of the much lower boiling point of the triisopropyl phosphite, between at least about 25°C and about 62°C, preferably between about 40°C and about 62 °C and most preferably between about 55°C and about 62°C, for from at least about 30 hours to at most about 100 hours, preferably for from at least about 50 hours to at most about 90 hours and most preferably for about 80 hours. The phosphonate ester of formula (D) : formula (D) where R 2 ^ is ethyl, methyl or isopropyl, and Pg and R are as defined previously; is then isolated and purified using standard techniques known in the art . The protected phosphonate ester of formula (D) can then be converted to the unprotected phosphonic acid of formula (E) : formula (E) where R is as defined previously; or it can be converted to an unprotected salt of a phosphonic acid of formula (F) : formula (F) where R° is a pharmaceutically acceptable cation and R is as defined previously; by converting the ester functional groups to either the acid or salt functional groups and by removing the protecting group ( s ) on the primary and secondary amino and -OH moieties in the remainder of the difluoronucleoside . In order to conduct these conversions it is necessary to select a synthetic pathway that will both deprotect the primary and secondary amino and -OH moieties and also cleave the phosphonate ester moieties to prepare the corresponding acid or salt. These steps can be conducted simultaneously or separately as is convenient or desired. Likewise, if it is the diester functionality that is desired, then the only remaining step in the synthesis is removal of the protecting groups . The removal of protecting groups and the conversion of a phosphonate ester functionality into either an acid or salt functionality are synthetic conversions known in the art of organic synthesis. For example, one way to convert a phosphonate ester of formula (D) to an ammonium salt of formula (G) formula (G) where R is as defined previously; is to contact the phosphonate ester of formula (D) with reagents suitable to remove the protecting groups and convert the ester moieties to salts. A suitable reagent combination for these reactions has been found to be bromotrimethylsilane followed by anhydrous ammonia. This reaction can be performed in a suitable non-reactive organic solvent such as acetonitrile . The bromotrimethylsilane reaction can take place at about room temperature of about 25°C and requires between about 2 hours and about 4 hours, preferably between about 2.5 hours and about 3 hours and most preferably about 2.5 hours. The diammonium salt is formed by contacting the phosphonic acid product of the above bromotrimethylsilane reaction with anhydrous ammonia and heating the reaction mixture between at least about 50°C and about 100°C, preferably between about 60°C and about 90°C and most preferably between about 70°C and about 90°C, for from at least about 10 hours to at most about 30 hours, preferably from at least about 15 hours to at most about 25 hours and most preferably for about 18 hours. The ammonium salt of formula (G) is then isolated and purified using standard techniques known in the art. As stated above, the present invention includes solvates of the compounds of formula (II) . A particular compound of the present invention may form solvates with water or common organic solvents. Such solvates are included within the scope of claimed compounds of the present invention. Also as stated above, the present invention includes pharmaceutically acceptable salts of the compounds of formula (II) . These salts may be made using standard salt forming reagents, previously listed. It is noteworthy that only the diester phosphonate derivatives can form salts in the usual manner, as the phosphonic diacid compounds are amphoteric and as as such are capable of protonating themselves . After the difluoronucleoside phosphonic acids or derivatives thereof are made, they can be tested for their antiviral and antineoplastic properties using standard techniques known in the art. A suitable test method to determine activity against Herpes simpl ex virus, type I, and type II, is described in U.S. Patent No. 4,808,614, Columns 18-19, which has been previously incorporated by reference. Suitable test methods for determining anti- neoplastic activity, are described in U.S. Patent No. 5,464,826, Columns 19-23, which has been previously incorporated by reference. In these test methods the compounds are tested for their ability to inhibit the growth of certain cancerous cell lines by the standard cytotoxicity screening tests involving cell lines CCRF-CEM. The results of these tests are given as "IC50" which is the concentration of compound giving 50% growth inhibition. The compounds of the present invention may be administered to any mammal. Of all mammals, it is believed that humans will benefit the most from administration of these compounds. As such, administration to humans is preferred. The compounds of the present invention are antineo-plastic agents. An embodiment of the present invention provides a method of treating susceptible neoplasms in mammals, preferably humans, in need of such treatment. The present compounds are useful in inhibiting the growth of neoplasms or "cancers", including, but not limited to, carcinoma, sarcoma, melanoma, colorectal, choriocarcinoma, prostate, leukemia, breast, squamous or small cell lung cancer, non-small cell lung cancer, ovarian, testicular, adenocarcinoma, epidermal, lymphosarcoma, pancreatic, head and neck, kidney, bone and liver cancer. The compounds of the present invention are also antiviral agents, suitable for use in mammals, preferably humans. The compounds are effective for the treatment of viral infections in general, and most particularly in the treatment of infections caused by viruses of the herpes genus. The compounds of the present invention can be administered orally, parenterally, or by means of insufflation or by insertion of a suppository. The compounds can be administered individually or in combination, preferably parenterally, and usually in the form of a pharmaceutical composition. Parenteral routes of administration include intramuscular, intrathecal, subcutaneous, intravenous, intra-arterial, intraorbital, intracapsular, intraspinal, and intrasternal . Oral dosage forms, including tablets and capsules, contain from 1 to 3000 mg of drug per unit dosage. Isotonic saline solutions containing 1-100 mg/mL can be used for parenteral administration . Compositions are prepared in a manner well known in the pharmaceutical art and comprise at least one active compound. Accordingly, the present invention also includes pharmaceutical compositions comprising as active ingredient one or more compounds of formula (II) associated with at least one pharmaceutically acceptable carrier, diluent or excipient. The present invention also includes pharmaceutical compositions comprising as active ingredient, one or more compounds of formula (II) and one or more oncolytic medicaments such as, but not limited to, gemcitabine hydrochloride, cisplatin, paclitaxel, carboplatin, 5-fluorouracil, doxorubicin, epirubicin, etoposide, vinorelbine, vincristine, vinblastine, vindesine, tamoxifen, methotrexate, and irinotecan hydrochloride, associated with at least one pharmaceutically acceptable carrier, diluent or excipient. In making the compositions of the present invention, as well as compositions containing one or more other compounds of formula (II), the active ingredients are usually mixed with an excipient, diluted by an excipient or enclosed within such a carrier which can be in the form of a capsule, sachet, paper or other container. When the excipient serves as a diluent, it may be a solid, semi-solid or liquid material which acts as a vehicle, carrier or medium for the active ingredient. Thus, the compositions can be in the form of tablets, pills, powders, elixirs, suspensions, emulsions, solutions, syrups, soft and hard gelatin capsules, suppositories, sterile injectable solutions and sterile packaged powders. Some examples of suitable excipients include lactose, dextrose, sucrose, sorbitol, mannitol, starches, gum arabic, calcium silicate, microcrystalline cellulose, polyvinyl-pyrrolidinone, cellulose, water, syrup, and methyl cellulose, the formulations can additionally include lubricating agents such as talc, magnesium stearate and mineral oil, wetting agents, emulsifying and suspending agents, preserving agents such as methyl- and propylhydroxybenzoates , sweetening agents or flavoring agents. The compositions of the invention can be formulated so as to provide quick, sustained or delayed release of the active ingredient after administration to the patient by employing procedures well known in the art. The compositions are preferably formulated in a unit dosage form with each dosage normally containing from about 0.1 milligrams per square meter of body surface area (mg/M 2 ) to about 3000 mg/M 2 , more usually about 10 mg/M 2 to about 250 mg/M 2 of the active ingredient. The term "unit dosage form" refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect in association with a suitable pharmaceutical excipient. However, it will be understood that the amount of the compound actually administered per unit of time, and the frequency of administration, will be determined by a physician or veterinarian in light of the relevant circumstances including the relative severity of a disease state, the choice of compound to be administered, the age, weight, and response of the individual patient, and the chosen route of administration. Therefore, the above dosage ranges are not intended to limit the scope of this invention in any way . The following formulation examples are illustrative only and are not intended to limit the scope of the invention in any way. "Active ingredient" means one or more compounds of formula (II) . Formulation 1 Hard gelatin capsules are prepared using the following ingredients: Quantity (mσ/capsule) Active ingredient 250 Starch, dried 200 Magnesium stearate .10 . Total 460 mg Formulation 2 A tablet is prepared using the ingredients below: Quantity (mσ/capsule) Active ingredient 250 Cellulose, micro crystalline 400 Silicon dioxide, fumed 10 Stearic acid _5 Total 665 mg The components are blended and compressed to form tablets each weighing 665 mg. Formulation 3 Tablets, each containing 60 mg of active ingredient, are made as follows: Quantity (mα/tablet ) Active ingredient 60 Starch 45 Micro crystalline cellulose 35 Polyvinylpyrrolidone (as 10% solution in water) 4 Sodium carboxymethyl starch 4.5 Magnesium stearate 0.5 Talc 1 Total 150 The active ingredient, starch and cellulose are passed through a No . 45 mesh U.S. sieve and mixed thoroughly. The aqueous solution containing polyvinylpyrrolidone is mixed with the resultant powder, and the mixture then is passed through a No . 14 mesh U.S. sieve. The granules so produced are dried at 50°C and passed through a No . 18 mesh U.S. sieve. The sodium carboxymethyl starch, magnesium stearate and talc, previously passed through a No . 60 mesh U.S. sieve, are then added to the granules which, after mixing, are compressed on a tablet machine to yield tablets each weighing 150 mg. Formulation 4 Capsules, each containing 80 mg of active ingredient, are made as follows: Quantity (mσ/capsule) Active ingredient 80 Starch 59 Micro crystalline cellulose 59 Magnesium stearate 2 Total 200 The active ingredient, cellulose, starch, and magnesium stearate are blended, passed through a No . 45 mesh U.S. sieve, and filled into hard gelatin capsules in 200 mg quantities. Formulation 5 Suppositories, each containing 225 mg of active ingredient, are made as follows: Quantity (mσ/unit ) Active ingredient 225 Saturated fatty acid glycerides 2 , 000 Total 2,225 The active ingredient is passed through a No . 60 mesh U.S. sieve and suspended in the saturated fatty acid glycerides previously melted using the minimum heat necessary. The mixture is then poured into a suppository mold of normal 2 g capacity and allowed to cool. Formulation 6 Suspensions, each containing 50 mg of active ingredient per 5 L dose, are made as follows: Quantity (mσ/unit) Active ingredient (s) 50 mg Sodium carboxymethyl 50 mg cellulose Syrup 1.25 mL Benzoic acid solution 0.10 mL Flavor q.v. Color q.v. Purified water to total 5 mL Formulation 7 An intravenous formulation may be prepared as follows: Quantity Active ingredient 100 mg Isotonic saline 1,000 mL The following examples are illustrative only and are not intended to limit the scope of the invention in any way . Examples The terms and abbreviations used in the instant examples have their normal meanings unless otherwise designated. For example: "°C" refers to degrees Celsius; "N" refers to normal or normality; "mol" refers to mole or moles; "mmol" refers to millimole or illimoles; "g" refers to gram or grams; "mg" refers to milligrams; "ml" refers to milliliter or milliliters; "mp" refers to melting point; "M" refers to molar or molarity; "Mass spec." refers to mass spectrometry; and "NMR" refers to nuclear magnetic resonance spectroscopy . Unless otherwise noted, all chemicals were reagent grade materials from commercial suppliers and were used without further purification. Example 1 Synthesis of 1 ' -desoxy-1 ' -β- (lH-2-oxo-4-amino-pyrimidin-l- yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate Step 1: Synthesis of 1 ' -desoxy-1 ' -β- (lH-2-oxo-4-amino- pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose: A suspension of 0.528 g (2.0 mmol) of gemcitabine, 3.32 g (lOmmol) of carbon tetrabromide and 2.63 g (10 mmol) of triphenylphosphine in 12 mL of 1, 3-dimethyl-3 , 4, 5, 6- tetrahydro-2 (IH) -pyrimidinone was heated in an oil bath at 60°C for 1 hour. The cloudy reaction was allowed to cool to 25°C, diluted with 20mL of methanol and concentrated in vacuo to an oil. The oil was slurried two times with hexanes (10 mL) two times with ether (10 mL) and two times with toluene (10 ml) and the solvents decanted and discarded. The residue was dried in vacuo (4.1 g) and purified by flash chromatography on silica gel using 2 column volumes of CH2CI2 followed by 5% methanol in CH2CI2 as eluent to obtain 0.87 g (100 %) of a residue which was characterized as Jl. β-anomer:lH NMR (300 MHz, CH3OD) 53.7-4.25 (series of m, 4H) , 5.98 Td,lH, J 5 6 =7.6 Hz, 5-H) ; 6.28 (t,l H, Jχ. /F =8Hz, l'-H); 7.66 (d, IH, J 5 . 6 = 7.6 Hz, 6-H) . Mass Spec. (FD+) m/e 326 (M+) . Step 2: Synthesis of 1 ' -desoxy-1 ' -β- (lH-2-oxo-4-acetamyl- pyrimidin-1-yl) -2 ' , 2 ' -difluoro-3 ' -acetoxy-5 ' -desoxy-5 ' - bromoribose: To a solution of 0.67 g (2.1 mmol) of 1 in 18 mL of pyridine at 0-5°C, were added 0.461 g (4.5 mmol) of acetic anhydride. After 18 hours at this temperature 1.0 L of methanol was added and the reaction was concentrated in vacuo . The residue was taken into toluene and the solvent was again removed in vacuo . The residue was adsorbed on silica gel with methanol and applied to the head of a column. The product was purified by flash chromatography using 2% methanol in CH2CI2 as eluent to yield 0.38 g (45%) of a residue which was characterized as 2.. 1 H NMR (300 MHz, CDCI3) δ2.19 (s, 3H) , 2.3 (s, 3H) ; 3.7 (dd, IH, Hz, 5B'-H), 3.78 (dd, IH, J 4' , 5A' =3.5 Hz, J gem = 13.2 Hz, 5A'-H). 4.35 (m, IH, H- 4') 5.35 (m, IH, H-3 ' ) 6.45 (t,lH, J=8Hz, 1 ' -H) 7.55 (d,lH, J 5 6 =7.6 Hz) 7.85 (d, IH, J 5 , 6 =7.6 Hz) 9.88 (s,lH, N-H) Mass Spec. (FDA m/c 410 (M+) . Step 3: Synthesis of 1 ' -desoxy-1 ' -β- (lH-2-oxo-4-acetamyl- pyrimidin-1-yl) -2 ' , 2 ' -difluoro-3 ' -acetoxy-5 ' -desoxyribose 5 ' -diethylphosphonate : CH 3 A solution of 0.38 g (0.93 mmol) of 2. in 7.2 mL of triethyl phosphite was heated at 160-170°C for 30 hours with nitrogen bubbling through the solution. The reaction was monitored by HPLC (250 mm Dynamax Siθ2, 5% methanol in CH2CI2, 1-0 mL/min) . Triethyl phosphite was removed in vacuo at 80-100°C. The residue was slurried with hexane and the solvent was decanted. The residue was dried in vacuo and purified by flash chromatography on silica gel using 4% methanol in ethyl acetate as eluent to obtain 0.21 grams (49%) of a residue which was characterized as 3 . . !H NMR (300 MHz, CH3OD) δl .3 (t,6H), 2.0 (s,6H); 2.39 ( , 2H, 5'H)4.0-4.28 (m, 6H) 5.92 (d,lH, J 5 , 6 =7.6 Hz, 5- H) 6.19 (t, IH, J=8Hz, l'-H) 7.65 (d, IH, J 5 , 6 =A6 Hz, H-6). Mass Spec. (FD+) m/e 468 (M+) . Step 4: Synthesis of 1 ' -desoxy-1 ' -β- (lH-2-oxo-4-amino- pyrimidin-1-yl) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5'- diammoniumphosphonate : 4 To 1.2 mL of CH3CN, which had been stirred over molecular sieves for 2 hours, was added 0.2 grams (0.43 mmol) of 3 . followed by 0.2 g (1.28 mmol) of bromotrimethylsilane. The thick suspension dissolved after an hour at 25°C and was stirred an additional 1.5 hours. The solvent was removed in vacuo and the residue was taken into 25 mL of 10-1 methanol/H2θ which was saturated with anhydrous ammonia and placed in a Paar bomb and heated in an oil bath at 80°C for 18 hours. The reaction was concentrated in vacuo and the residue was dissolved in ethyl acetate and washed with water. The organic layer was concentrated in vacuo to obtain 0.1 g (65%) of a residue characterized as 4.. The named compound eluted at 4.67 minutes on a 250 mm Whatman Sax column (0.05M NH4H2PO4, pH=3.0, 1.0 ml/min) . 13 C NMR (D20) 532.31 (JcP =131.71, C-5 ' ) , 75.26 (C-3 ' ) , 77.60 (C-4 1 ), 85.75 (JcF = 24.09/38.55 C-l ' ) , 97.16 (C-2 ' ) , 123.05 (JCF = 258.60/258.60, C-2 1 ), 142.46 (C-6), 157.58 (C- 2) , 166.66 (C-4) . Test Results The compound of Example 1, Step 4 was tested against the human leukemia cell line (CCRF-CEM) according to the method described in U.S. Patent 5,464,826 (columns 19-20). The IC50 was found to be 0.3 μg/ml . The compound of Example 1, step 4 was tested against the Herpes simpl ex virus, type I (HSV-1) and Herpes simplex virus, type II (HSV-2); using the test method described in U.S. Patent No. 4,808,614, columns 18-19. The compound exhibited anti-viral activity against both HSV- 1 and HSV-2.

Claims: -3 ! What is claimed is 1. A compound of formula (II! where R i s a base selected f rom the group cons ist ing of : 11 (iii! wherein : R- 1 is hydrogen, methyl, bromo, fluoro, chloro or iodo; R 2 is hydroxy or -NR^R5 , where R^ and R^ are independently selected from the group consisting of hydrogen, methyl, ethyl and propyl ; R 3 is hydrogen, bromo, chloro or iodo; both R^ are the same, and are either -OR 7 or -(0 ~ R^), where R 7 is selected from the group consisting of hydrogen, methyl, ethyl, and isopropyl; R8 is a pharmaceutically acceptable cation; and pharmaceutically acceptable salts and solvates thereof. 2. A compound of Claim 1 in which the stereochemical orientation between the carbohydrate derivative ring and the base is in the beta configuration, as depicted in formula (lib) : A compound of Claim 1 in which R is A compound of Claim 3 in which R^ is (O-R* 5. A compound of Claim 4 in which R° is ammonium (NH4 + ) 6. The compound, 1 ' -desoxy-1 ' -β- ( lH-2-oxo-4- amino-pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' diammoniumphosphonate, which has the formula: 7. A compound of Claim 1 selected from the group consisting of: 1A) 1 ' -desoxy-1 '-(1,3 -dihydro-2 , 4-dioxo-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IB) 1 ' -desoxy-1 '-(1,3 -dihydro-2 , 4-dioxo-5-methyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IC) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-bromo-pyrimidin-l- yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; ID) 1 ' -desoxy-1 ' - ( 1 , 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- 1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IE) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-chloro-pyrimidin- 1-yl) -2 ', 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IF) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-pyrimidin-l-yl ) -2 ' , 2 ' - difluoro-5 ' -desoxy-5 ' -phosphono ribose; IG) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-methyl-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IH) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-1-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; II) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-fluoro-pyrimidin-1-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IJ) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-chloro-pyrimidin-l-yl ) - 2 ', 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IK) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IL) 1 ' -desoxy-1 ' - (guanin-9-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' - phosphono ribose; 1M) 1 ' -desoxy-1 ' - ( l-dehydro-2-desamino-6-desoxo-6- aminoguanin-9-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IN) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl) -2 ', 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; 10) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-iodoethylenyl ) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; IP) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-chloroethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; 1Q) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-bromoethylenyl) - pyrimidin-1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -phosphono ribose; 2A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-methyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-bromo-pyrimidin-l- yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2D) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2E) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-chloro-pyrimidin- 1-yl ) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2F) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-pyrimidin-l-yl) -2 ' , 2 ' - difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2G) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5-methyl-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2H) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-l-yl) - 2 ' , 2 ' -difluo-5 ' -desoxyribose 5 ' -dimethylphosphonate; 21) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-fluoro-pyrimidin-1-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2J) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5-chloro-pyrimidin-l-yl ) - 2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2K) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate; 2L ) 1 ' -desoxy-1 ' - ( guanin- 9 -yl ) -2 ' , 2 ' -di f luoro-5 ' - desoxyribose 5 ' -dimethylphosphonate; 2M) 1 ' -desoxy-1 ' - (l-dehydro-2-desamino-6-desoxo-6- aminoguanin-9-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - dimethylphosphonate; 2N) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -dimethylphosphonate ; 20) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- ( 2-iodoethylenyl) - pyrimidin-1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - dimethylphosphonate; 2P) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-hydroxy-5- (2-chloroethylenyl ) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - dimethylphosphonate ; 2Q) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-bromoethylenyl ) - pyrimidin-1-yl) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5'- dimethylphosphonate ; 3A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-methyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-bromo-pyrimidin-l- yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3D) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- 1-yl) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3E) 1 ' -desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-5-chloro-pyrimidin- 1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3F) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-pyrimidin-l-yl ) -2 ' , 2 ' - difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3G) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-methyl-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3H) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 31) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-fluoro-pyrimidin-1-yl) - 2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3J) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-chloro-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 3K) 1 ' -desoxy-1 ' - ( lH-2 -oxo-4-amino-5 -iodo-pyrimidin-l -yl ) - 2 ' , 2 ' -di f luoro-5 ' -desoxyribose 5 ' -diethylphosphonate ; 3D 1 ' -desoxy-1 ' - ( guanin-9 -yl ) -2 ' , 2 ' -di f luoro-5 ' - desoxyribose 5 ' -diethylphosphonate; 3M) 1 ' -desoxy-1 ' - ( l-dehydro-2-desamino-6-desoxo-6- aminoguanin-9-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diethylphosphonate ; 3N) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diethylphosphonate; 30) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-iodoethylenyl) - pyrimidin-1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diethylphosphonate ; 3P) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-chloroethylenyl) - pyrimidin-1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diethylphosphonate; 3Q) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-bromoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diethylphosphonate ; 4A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-methyl-pyrimidin- 1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-5-bromo-pyrimidin-l- yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4D) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropyl- phosphonate; 4E) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-chloro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4F) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-pyrimidin-l-yl) -2 ' , 2 ' - difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4G) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-methyl-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4H) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 41) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5-fluoro-pyrimidin-1-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4J) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-chloro-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4K) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate; 4L) 1 ' -desoxy-1 ' - (guanin-9-yl ) -2 ' , 2 ' -difluoro-5 ' - desoxyribose 5 ' -diisopropylphosphonate; 4M) 1 ' -desoxy-1 ' - ( l-dehydro-2-desamino-6-desoxo-6- aminoguanin-9-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diisopropylphosphonate; 4N) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl ) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -diisopropylphosphonate, • 40) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-iodoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diisopropylphosphonate; 4P) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-chloroethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diisopropylphosphonate ; 4Q) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-hydroxy-5- (2-bromoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diisopropylphosphonate; pharmaceutically acceptable salts; pharmaceutically acceptable solvates; and mixtures thereof . 8. A compound of Claim 1 selected from the group consisting of: 5A) 1 ' -desoxy-1 '-(1,3 -dihydro-2 , 4-dioxo-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate; 5B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-methyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diammoniumphosphonate ; 5C ) 1 ' -desoxy-1 ' - ( 1 , 3 -dihydro-2 , 4 -dioxo- 5 -bromo-pyrimidin-l - yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate; 5D) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- 1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diammoniumphosphonate; 5E) 1 ' -desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-5-chloro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diammoniumphosphonate ; 5F) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-pyrimidin-l-yl) -2 ' , 2 ' - difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate; 5G) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-methyl-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate; 5H) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5-brorno-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate; 51) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-fluoro-pyrimidin-1-yl ) - 2 ' ,2 ' -difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate; 5J) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-chloro-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate; 5k) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -diammoniumphosphonate; 5L) 1 ' -desoxy-1 ' - (guanin-9-yl) -2 ' , 2 ' -difluoro-5 ' - desoxyribose 5 ' -diammoniumphosphonate; 5M) 1 ' -desoxy-1 ' - (l-dehydro-2-desamino-6-desoxo-6- aminoguanin-9-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diammoniumphosphonate ; 5N) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diammoniumphosphonate ; 50) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-iodoethylenyl) - pyrimidin-1-yl) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5'- diammoniumphosphonate ; 5P) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-hydroxy-5- (2-chloroethylenyl ) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diammoniumphosphonate ; 5Q) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-bromoethylenyl ) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - diammoniumphosphonate ; 6A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-5-methyl-pyrimidin- 1-yl) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-5-bromo-pyrimidin-l- yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6D) 1 ' -desoxy-1 ' - ( 1 , 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- 1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6E) 1 ' -desoxy-1 ' - (1, 3-dihydro-2, 4-dioxo-5-chloro-pyrimidin- 1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6F) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-pyrimidin-l-yl) -2 ' , 2 ' - difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6G) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5-methyl-pyrimidin-l-yl ) - 2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6H) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 61) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-fluoro-pyrimidin-1-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6J) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-chloro-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6K) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 6L) 1 ' -desoxy-1 ' - (guanin-9-yl ) -2 ' , 2 ' -difluoro-5 ' - desoxyribose 5 ' -disodiumphosphonate; 6M) 1 ' -desoxy-1 ' - ( l-dehydro-2-desamino-6-desoxo-6- aminoguanin-9-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - disodiumphosphonate ; 6N) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5 ' -disodiumphosphonate; 60) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-iodoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - disodiumphosphonate ; 6P) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-hydroxy-5- (2-chloroethylenyl) - pyrimidin-1-yl ) -2 ', 2 ' -difluoro-5 ' -desoxyribose 5'- disodiumphosphonate ; 6Q) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-bromoethylenyl ) pyrimidin-1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxyribose 5 ' - disodiumphosphonate; pharmaceutically acceptable solvates; and mixtures thereof . 9. A compound of formula (B) where X is -Cl, -Br, or -I, and R is a base selected from the group consisting of iii ) in : iv) (v) wherein: R 1 is hydrogen, methyl, bromo, fluoro, chloro or iodo; R 2 is hydroxy or -NRR 5 , where R 4 and R 5 are independently selected from the group consisting of hydrogen, methyl, ethyl and propyl ; and R 3 is hydrogen, bromo, chloro or iodo. 10. A compound of Claim 9 selected from the group consisting of: 7A) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-pyrimidin-l-yl) -2 ' ,2 ' - difluoro-5 ' -desoxy-5 ' -bromoribose; 7B) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-pyrimidin-l-yl ) -2 ' , 2 ' - difluoro-5 ' -desoxy-5 ' -chlororibose; 7C) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-pyrimidin-l-yl ) -2 ' , 2 ' - difluoro-5 ' -desoxy-5 ' -iodoribose; 8A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 8B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-pyrimidin-l-yl ) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 8C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 9A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-methyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 9B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-methyl-pyrimidin- 1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 9C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-methyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 10A) 1 ' -desoxy-1 ' - (guanin-9-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' - bromoribose; 10B) 1 ' -desoxy-1 ' - (guanin-9-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' - chlororibose; 10C) 1 ' -desoxy-1 '- (guanin-9-yl ) -2 ' ,2 ' -difluoro-5 ' -desoxy-5 ' - iodoribose; 11A) 1 ' -desoxy-1 ' - (l-dehydro-2-desamino-6-desoxo-6-amino- guanin-9-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 11B) 1 ' -desoxy-1 ' - (l-dehydro-2-desamino-6-desoxo-6-amino- guanin-9-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 11C) 1 ' -desoxy-1 ' - (l-dehydro-2-desamino-6-desoxo-6-amino- guanin-9-yl) -2 ' , 2 ' -dif luoro-5 ' -desoxy-5 ' -iodoribose; 12A) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl) -2 ' , 2 ' -dif luoro-5 ' -desoxy-5 ' -bromoribose; 12B) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl) -2 ' , 2 ' -dif luoro-5 ' -desoxy-5 ' -chlororibose; 12C) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5-ethylenyl-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 13A) 1 ' -desoxy-1 ' - (1 , 3-dihydro-2 , 4-dioxo-5-bromo-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 13B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-bromo-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 13C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-bromo-pyrimidin- 1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 14A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 14B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- 1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 14C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-fluoro-pyrimidin- l-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 15A) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-chloro-pyrimidin- 1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 15B) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-chloro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 15C) 1 ' -desoxy-1 ' - (1, 3-dihydro-2 , 4-dioxo-5-chloro-pyrimidin- 1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 16A) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 16B) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-l-yl ) - 2 ', 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 16C) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-bromo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 17A) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5-fluoro-pyrimidin-1- yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 17B) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-fluoro-pyrimidin-1- yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 17C) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-fluoro-pyrimidin-1- yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 18A) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5-chloro-pyrimidin-l- yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 18B) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-chloro-pyrimidin-l- yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 18C) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-chloro-pyrimidin-l- yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose ; 19A) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 19B) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 19C) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5-iodo-pyrimidin-l-yl) - 2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 20A) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-iodoethylenyl ) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 20B) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5- (2-iodoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 20C) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5- (2-iodoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 21A) l'-desoxy-l'-(lH-2-oxo-4-hydroxy-5-(2-chloroethylenyl) pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 2IB) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5- (2-chloroethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 21C) 1 ' -desoxy-1 ' - ( lH-2-oxo-4-amino-5- (2-chloroethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; 22A) 1 ' -desoxy-1 ' - (lH-2-oxo-4-hydroxy-5- (2-bromoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -bromoribose; 22B) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5- (2-bromoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -chlororibose; 22C) 1 ' -desoxy-1 ' - (lH-2-oxo-4-amino-5- (2-bromoethylenyl) - pyrimidin-1-yl) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' -iodoribose; and pharmaceutically acceptable salts; pharmaceutically acceptable solvates; and mixtures thereof . 11. The compound, 1 ' -desoxy-1 ' -β- (lH-2-oxo-4- amino-pyrimidin-1-yl ) -2 ' , 2 ' -difluoro-5 ' -desoxy-5 ' - bromoribose, which has the formula: 12. A method of treating susceptible neoplasms in mammals comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Claim 1. 13. A method of treating Herpes viral infections in mammals comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Claim 1. 14. A pharmaceutical composition comprising one or more compounds of Claim 1 in combination with pharmaceutically acceptable excipients and/or diluents.

Inventors: HERTEL LARRY W, KROIN JULIAN S, HERTEL, LARRY, W., KROIN, JULIAN, S.
Applicants: HERTEL LARRY W, KROIN JULIAN S, LILLY CO ELI, ELI LILLY AND COMPANY, HERTEL, LARRY, W., KROIN, JULIAN, S.
Application year: 1998
Main classification: A61K31
IPC codes: A61K31, A61P31, A61P35, C07H19