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Claims for Patent: 8,334,270

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Claims for Patent: 8,334,270

Title:Nucleoside phosphoramidate prodrugs
Abstract: Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure: ##STR00001## Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.
Inventor(s): Sofia; Michael Joseph (Doylestown, PA), Du; Jinfa (New Hope, PA), Wang; Peiyuan (Glen Rock, NJ), Nagarathnam; Dhanapalan (Bethany, CT)
Assignee: Gilead Pharmasset LLC (Foster City, CA)
Application Number:13/099,671
Patent Claims: 1. A compound selected from among (S)-methyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)propanoate; (S)-methyl 2-(((R)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)propanoate; methyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)acetate; methyl 2-(((R)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)acetate; (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)propanoate; (S)-isopropyl 2-(((R)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)propanoate; (S)-isopropyl 2-(((S)-(4-chlorophenoxy)(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidi- n-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)phosph- oryl)amino)propanoate; (S)-isopropyl 2-(((R)-(4-chlorophenoxy)(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidi- n-1(2H)-yl)-4-fluoro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)phosph- oryl)amino)propanoate; (S)-cyclohexyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)propanoate; (S)-cyclohexyl 2-(((R)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)propanoate; (S)-cyclohexyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(4-fluorophenoxy)phosph- oryl)amino)propanoate; and (S)-cyclohexyl 2-(((R)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(4-fluorophenoxy)phosph- oryl)amino)propanoate.

2. The compound of claim 1 selected from among (S)-methyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)propanoate; (S)-methyl 2-(((R)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)propanoate; (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)propanoate; (S)-isopropyl 2-(((R)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)propanoate; (S)-cyclohexyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(4-fluorophenoxy)phosph- oryl)amino)propanoate; and (S)-cyclohexyl 2-(((R)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(4-fluorophenoxy)phosph- oryl)amino)propanoate.

3. The compound of claim 1 selected from among (S)-isopropyl 2-(((R)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)propanoate.

4. The compound of claim 1 selected from among (S)-methyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)propanoate and (S)-methyl 2-(((R)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)propanoate.

5. The compound of claim 4 selected from among (S)-methyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)propanoate.

6. The compound of claim 4 selected from among (S)-methyl 2-(((R)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)ami- no)propanoate.

7. The compound of claim 1 selected from among (S)-cyclohexyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(4-fluorophenoxy)phosph- oryl)amino)propanoate; and (S)-cyclohexyl 2-(((R)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(4-fluorophenoxy)phosph- oryl)amino)propanoate.

8. The compound of claim 7 selected from among (S)-cyclohexyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(4-fluorophenoxy)phosph- oryl)amino)propanoate.

9. The compound of claim 7 selected from among (S)-cyclohexyl 2-(((R)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-flu- oro-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(4-fluorophenoxy)phosph- oryl)amino)propanoate.

10. A pharmaceutical composition comprising the compound according to claim 1.

11. The pharmaceutical composition according to claim 10 further comprising a pharmaceutically acceptable medium.

12. The pharmaceutical composition according to claim 11 comprising an effective amount of the compound according to claim 1 to treat a hepatitis C virus infection.

13. A method of treating a subject infected by a virus selected from among hepatitis C virus, West Nile virus, a yellow fever virus, a dengue virus, a rhinovirus, a polio virus, a hepatitis A virus, a bovine viral diarrhea virus, and a Japanese encephalitis virus, which comprises administering to the subject an effective amount of the compound according to claim 1.

14. The method of claim 13 wherein the virus is hepatitis C virus.

15. The method of claim 14, which further comprises administering to the subject an effective amount of another antiviral agent.

16. A compound or its stereoisomer thereof selected from among (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-3-methyl-butyric acid methyl ester; (S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrim- idin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosp- horylamino}-3-methyl-butyric acid methyl ester; (S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrim- idin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosp- horylamino}-propionic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid ethyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalen-1-yloxy)-ph- osphorylamino}-propionic acid benzyl ester; {[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hy- droxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-acet- ic acid methyl ester; (S)-2-{(2,4-Dichloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-- pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-- phosphorylamino}-propionic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalen-1-yloxy)-ph- osphorylamino}-propionic acid methyl ester; (S)-1-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphoryl}-pyr- rolidine-2-carboxylic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3 -hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamin- o}-propionic acid butyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid benzyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid methyl ester; (S)-2-{(4-Chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyri- midin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phos- phorylamino}-propionic acid methyl ester; (S)-2-{(3,4-Dichloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-- pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-- phosphorylamino}-propionic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid sec-butyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid isopropyl ester; (S)-2-{[(2R,3 R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4- -methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-phosphorylamino}- -propionic acid butyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid ethyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid benzyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-pho- sphorylamino}-propionic acid isopropyl ester; (S)-2-{(2-Chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyri- midin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phos- phorylamino}-propionic acid benzyl ester; (S)-2-{(2,4-Dichloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-- pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-- phosphorylamino}-propionic acid butyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylam- ino}-propionic acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid butyl ester; (S)-2-{(3,4-Dichloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-- pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-- phosphorylamino}-propionic acid ethyl ester; (S)-2-{(2-Chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyri- midin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phos- phorylamino}-propionic acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-pho- sphorylamino}-propionic acid benzyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid pentyl ester; (S)-2-{(4-Chloro-phenoxy)-[(2R,3R,4 R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-me- thyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-propionic acid isopropyl ester; (S)-2-{(4-Chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyri- midin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phos- phorylamino}-propionic acid butyl ester; (S)-2-{(4-Chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyri- midin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phos- phorylamino}-propionic acid ethyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylam- ino}-propionic acid butyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylam- ino}-propionic acid benzyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-butyric acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid 4-fluoro-benzyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid 3-methyl-butyl ester; (S)-2-{(2,4-Dichloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-- pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-- phosphorylamino}-propionic acid ethyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid cyclohexyl ester; (S)-2-{(2-Chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyri- midin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phos- phorylamino}-propionic acid butyl ester; (S)-2-{(4-Bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrim- idin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosp- horylamino}-propionic acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid cyclohexyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-bromo-phenoxy)-phosp- horylamino}-propionic acid cyclohexyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-butyric acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-butyric acid cyclohexyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-butyric acid cyclohexyl ester; (S)-2-{(4-Chloro-phenoxy)-[(2R,3R,4 R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-me- thyl-tetrahydro-furan-2-ylmethoxy]-phosphorylamino}-butyric acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-- 4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphor- ylamino}-propionic acid 2,2-difluoro-ethyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid 2,2,2-trifluoro-1-trifluoromethyl-ethyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid 2-fluoro-1-fluoromethyl-ethyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid cyclopropyl methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-butyric acid cyclopentyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(3,4-dichloro-phenoxy)-- phosphorylamino}-propionic acid benzyl ester; and (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid 2-fluoro-ethyl ester.

17. The compound of claim 16 or its stereoisomer thereof selected from among (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4- -fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphory- lamino}-propionic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-3-methyl-butyric acid methyl ester; (S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrim- idin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosp- horylamino}-3-methyl-butyric acid methyl ester; (S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrim- idin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosp- horylamino}-propionic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid ethyl ester; {[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hy- droxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-acet- ic acid methyl ester; (S)-2-{(2,4-Dichloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-- pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-- phosphorylamino}-propionic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalen-1-yloxy)-ph- osphorylamino}-propionic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid butyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid benzyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid methyl ester; (S)-2-{(4-Chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyri- midin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phos- phorylamino}-propionic acid methyl ester; (S)-2-{(3,4-Dichloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-- pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-- phosphorylamino}-propionic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid sec-butyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-pho- sphorylamino}-propionic acid butyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid ethyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid benzyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-pho- sphorylamino}-propionic acid isopropyl ester; (S)-2-{(2-Chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyri- midin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phos- phorylamino}-propionic acid benzyl ester; (S)-2-{(2,4-Dichloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-- pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-- phosphorylamino}-propionic acid butyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylam- ino}-propionic acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid butyl ester; (S)-2-{(3,4-Dichloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-- pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-- phosphorylamino}-propionic acid ethyl ester; (S)-2-{(2-Chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyri- midin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phos- phorylamino}-propionic acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-pho- sphorylamino}-propionic acid benzyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid pentyl ester; (S)-2-{(4-Chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyri- midin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phos- phorylamino}-propionic acid isopropyl ester; (S)-2-{(4-Chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyri- midin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phos- phorylamino}-propionic acid butyl ester; (S)-2-{(4-Chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyri- midin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phos- phorylamino}-propionic acid ethyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylam- ino}-propionic acid butyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylam- ino}-propionic acid benzyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-butyric acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid 4-fluoro-benzyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid 3-methyl-butyl ester; (S)-2-{(2,4-Dichloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-- pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-- phosphorylamino}-propionic acid ethyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid cyclohexyl ester; (S)-2-{(2-Chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyri- midin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phos- phorylamino}-propionic acid butyl ester; (S)-2-{(4-Bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrim- idin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosp- horylamino}-propionic acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid cyclohexyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-bromo-phenoxy)-phosp- horylamino}-propionic acid cyclohexyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-butyric acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-butyric acid cyclohexyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-butyric acid cyclohexyl ester; (S)-2-{(4-Chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyri- midin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phos- phorylamino}-butyric acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid cyclopropyl methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-butyric acid cyclopentyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(3,4-dichloro-phenoxy)-- phosphorylamino}-propionic acid benzyl ester; and (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid 2-fluoro-ethyl ester.

18. The compound of claim 17 or its stereoisomer thereof selected from among (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4- -fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphory- lamino}-propionic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-3-methyl-butyric acid methyl ester; (S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrim- idin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosp- horylamino}-3-methyl-butyric acid methyl ester; (S)-2-{(4-bromo-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrim- idin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phosp- horylamino}-propionic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid ethyl ester; {[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluoro-3-hy- droxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino}-acet- ic acid methyl ester; (S)-2-{(2,4-Dichloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-- pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-- phosphorylamino}-propionic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalen-1-yloxy)-ph- osphorylamino}-propionic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid butyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid benzyl ester; (S)-2-{(4-Chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyri- midin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phos- phorylamino}-propionic acid methyl ester; (S)-2-{(3,4-Dichloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-- pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-- phosphorylamino}-propionic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid sec-butyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid ethyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-pho- sphorylamino}-propionic acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylam- ino}-propionic acid isopropyl ester; (S)-2-{(3,4-Dichloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-- pyrimidin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-- phosphorylamino}-propionic acid ethyl ester; (S)-2-{(2-Chloro-phenoxy)-[(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyri- midin-1-yl)-4-fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phos- phorylamino}-propionic acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-pho- sphorylamino}-propionic acid benzyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid pentyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylam- ino}-propionic acid butyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-p-tolyloxy-phosphorylam- ino}-propionic acid benzyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-butyric acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid 3-methyl-butyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid cyclohexyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-butyric acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-butyric acid cyclohexyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-butyric acid cyclohexyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid cyclohexyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid cyclopropyl methyl ester; and (S)-2-{[(2R,3R,4R,SR)-S-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-butyric acid cyclopentyl ester.

19. The compound of claim 18 or its stereoisomer thereof selected from among (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4- -fluoro-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphory- lamino}-propionic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(naphthalen-1-yloxy)-ph- osphorylamino}-propionic acid methyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid ethyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-methoxy-phenoxy)-pho- sphorylamino}-propionic acid isopropyl ester; (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-phenoxy-phosphorylamino- }-propionic acid cyclohexyl ester; and (S)-2-{[(2R,3R,4R,5R)-5-(2,4-Dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-fluor- o-3-hydroxy-4-methyl-tetrahydro-furan-2-ylmethoxy]-(4-fluoro-phenoxy)-phos- phorylamino}-propionic acid cyclohexyl ester.

20. A pharmaceutical composition comprising the compound according to claim 16.

21. The pharmaceutical composition according to claim 20 further comprising a pharmaceutically acceptable medium.

22. The pharmaceutical composition according to claim 21 comprising an effective amount of the compound according to claim 16 to treat a hepatitis C virus infection.

23. A method of treating a subject infected by a virus selected from among hepatitis C virus, West Nile virus, a yellow fever virus, a dengue virus, a rhinovirus, a polio virus, a hepatitis A virus, a bovine viral diarrhea virus, and a Japanese encephalitis virus, which comprises administering to the subject an effective amount of the compound according to claim 16.

24. The method of claim 23 wherein the virus is hepatitis C virus.

25. The method of claim 24, which further comprises administering to the subject an effective amount of another antiviral agent.
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