Nucleotide mimics and their prodrugs

• US 20040059104A1
• Filed: 02/28/2003
• Published: 03/25/2004
• Est. Priority Date: 02/28/2002
• Status: Active Grant

• Current Assignee: Biota Scientific Management Pty Limited (Vaxart, Inc.)
• Original Assignee: Biota Scientific Management Pty Limited (Vaxart, Inc.)
• Inventors: Jin, Yi, Cook, Phillip Dan, Brooks, Jennifer L., Wang, Guangyi, Ariza, Maria Eugenia, Prhavc, Marija, Fagan, Patrick C., Rajwanshi, Vivek K., Bruice, Thomas W., Tucker, Kathleen D., Boyle, Nicholas A., Leeds, Janet M.
• Granted Patent: US 7,285,658 B2
• Time in Patent Office: Days
• US Class Current: 536/26.1
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/14 Pyrrolo-pyrimidine radicals
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids

Abstract

The present invention relates to nucleoside diphosphate mimics and nucleoside triphosphate mimics, which contain diphosphate or triphosphate moiety mimics and optionally sugar-modifications and/or base-modifications. The nucleotide mimics of the present invention, in a form of a pharmaceutically acceptable salt, a pharmaceutically acceptable prodrug, or a pharmaceutical formulation, are useful as antiviral, antimicrobial, and anticancer agents. The present invention provides a method for the treatment of viral infections, microbial infections, and proliferative disorders. The present invention also relates to pharmaceutical compositions comprising the compounds of the present invention optionally in combination with other pharmaceutically active agents.

Claims

1. A compound of Formula (I) which may be a D- or L-nucleotide:

2. The compound defined in claim 1 of Formula (V):

3. The compound defined in claim 1 of Formula (VI):

4. The compound defined in claim 1 of Formula (VII):

5. The compound defined in claim 4

wherein X² is O;

and

wherein X⁷ is SH, NH₂, ⁻

BH₃M⁺, alkyl, aryl, alkylamino, or arylamino.

6. The compound defined in claim 4

wherein X² is O;

and

wherein X⁷ is selected from the group consisting of SH, NH₂, ⁻

BH₃M⁺, R, and NHR.

7. The compound defined in claim 1 of Formula (VIII):

8. The compound defined in claim 1 of Formula (VIII):

wherein X⁹ and X¹⁰ are selected independently from the group consisting of acylthioethoxy, acyloxymethoxy, 1,2-O-diacylglyceroxy, 1,2-O-dialkylglyceroxy, and 1-O-alkyl-2-O-acylglyceroxy.

9. The compound defined in claim 1 of Formula (VIII):

10. The compound defined in claim 8 wherein at least one of X⁹ and X¹⁰ is 1,2-O-dialkylglyceryloxy.

11. The compound defined in claim 1 of Formula (IX):

13. The compound defined in claim 1 of Formula (X):

14. The compound defined in claim 1 of Formula (X):

15. The compound defined in claim 1 of Formula (XI):

16. The compound defined in claim 1 of Formula (XI):

17. The compound defined in claim 1 of Formula (XII):

18. The compound defined in claim 1 of Formula (XII):

19. The compound defined in claim 1 of Formula (XIII):

20. The compound defined in claim 1 of Formula (XIII):

21. The compound defined in claim 1 of Formula (XIV):

22. The compound defined in claim 1 of Formula (XIV):

23. The compound defined in claim 1 of Formula (XV):

24. The compound defined in claim 1 of Formula (XV):

55. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 1, a pharmaceutically acceptable salt thereof, optionally in combination with one or more other active ingredients and/or with a pharmaceutically acceptable carrier

57. A method for the treatment of a microbial infection comprising administering a therapeutically effective amount of the compound defined in claim 1.

58. A method for the treatment of a proliferative disorder comprising administering a therapeutically effective amount of the compound defined in claim 1.

12. The compound defined in 1 of Formula (IX):

25. A compound of Formula (XVI):

26. The compound defined in claim 25 where Nu is selected from the group consisting of:

adenosine,

cytidine,

guanosine,

uridine,

2′

-deoxyadenosine,

2′

-deoxycytidine,

2′

-deoxyguanosine,

thymidine,

inosine,

9-(β

-D-arabinofuranosyl)adenine,

1-(β

-D-arabinofuranosyl)cytosine,

9-(β

-D-arabinofuranosyl)guanine,

1-(β

-D-arabinofuranosyl)uracil,

9-(β

-D-arabinofuranosyl)hypoxanthine,

1-(β

-D-arabinofuranosyl)thymine,

3′

-azido-3′

-deoxythymidine,

3′

-azido-2′

,3′

-dideoxyuridine,

3′

-azido-2′

,3′

-dideoxycytidine,

3′

-azido-2′

,3′

-dideoxyadenosine,

3′

-azido-2′

,3′

-dideoxyguanosine,

3′

-azido-2′

,3′

-dideoxyinosine,

3′

-deoxythymidine,

2′

,3′

-dideoxyuridine,

2′

,3′

-dideoxyinosine,

2′

,3′

-dideoxyadenosine,

2′

,3′

-dideoxycytidine,

2′

,3′

-dideoxyguanosine,

9-(2,3-dideoxy-1-β

-D-ribofuranosyl)-2,6-diaminopurine,

3′

-deoxy-2′

,3′

-didehydrothymidine,

2′

,3′

-didehydro-2′

,3′

-dideoxyuridine,

2′

,3′

-didehydro-2′

,3′

-dideoxycytidine,

2′

,3′

-didehydro-2′

,3′

-dideoxyadenosine,

2′

,3′

-didehydro-2′

,3′

-dideoxyguanosine,

2′

,3′

-didehydro-2′

,3′

-dideoxyinosine,

3-deazaadenosine,

3-deazaguanosine,

3-deazainosine,

7-deazaadenosine,

7-deazaguanosine,

7-deazainosine,

6-azauridine,

6-azathymidine,

6-azacytidine,

5-azacytidine,

9-(β

-D-ribofuranosyl)-6-thiopurine,

6-methylthio-9-(β

-D-ribofuranosyl)purine,

2-amino-9-(β

-D-ribofuranosyl)-6-thiopurine,

2-amino-6-methylthio-9-(β

-D-ribo furanosyl)purine,

5-fluorocytidine,

5-iodocytidine,

5-bromocytidine,

5-chlorocytidine,

5-fluorouridine,

5-iodouridine,

5-bromouridine,

5-chlorouridine,

2′

-C-methyladenosine,

2′

-C-methylcytidine,

2′

-C-methylguanosine,

2′

-C-methylinosine,

2′

-C-methyluridine,

2′

-C-methylthymidine,

2′

-deoxy-2′

-fluoroadenosine,

2′

-deoxy-2′

-fluorocytidine,

2′

-deoxy-2′

-fluoroguanosine,

2′

-deoxy-2′

-fluorouridine,

2′

-deoxy-2′

-fluoroinosine,

2′

-β

-fluorothymidine,

2′

-deoxy-2′

-fluoroarabinoadenosine,

2′

-deoxy-2′

-fluoroarabinocytidine,

2′

-deoxy-2′

-fluoroarabinoguanosine,

2′

-deoxy-2′

-fluoroarabinouridine,

2′

-deoxy-2′

-fluoroarabinoinosine,

2′

-β

-fluorothymidine,

2′

-O-methyladenosine,

2′

-O-methylcytidine,

2′

-O-methylguanosine,

2′

-O-methylinosine,

2′

-O-5-dimethyluridine,

2′

-C-ethynylcytidine,

2′

-C-ethynylguanosine,

2′

-C-ethynyluridine,

2′

-C-ethynylinosine,

2′

-C-ethynyl-5-methyluridine,

3′

-C-ethynyladenosine,

3′

-C-ethynylcytidine,

3′

-C-ethynylguanosine,

3′

-C-ethynyluridine,

3′

-C-ethynylinosine,

3′

-C-ethynyl-5-methyluridine,

3′

-deoxyadenosine,

3′

-deoxycytidine,

3′

-deoxyguanosine,

3′

-deoxytridine,

3′

-deoxyinosine,

4′

-C-ethynyladenosine,

4′

-C-ethynylcytidine,

4′

-C-ethynylguanosine,

4′

-C-ethynyluridine,

4′

-C-ethynylinosine,

4′

-C-ethynylthymidine,

4′

-C-methyladenosine,

4′

-C-methylcytidine,

4′

-C-methylguanosine,

4′

-C-methyluridine,

4′

-C-methylinosine,

4′

-C-methylthymidine,

2′

-C-methyl-7-deazaadenosine,

2′

-C-methyl-7-deazaguanosine,

2′

-C-methyl-3-deazaadenosine,

2′

-C-methyl-3-deazaguanosine,

2′

-O-methyl-7-deazaadenosine,

2′

-O-methyl-7-deazaguanosine,

2′

-O-methyl-3-deazaadenosine,

2′

-O-methyl-3-deazaguanosine,

2′

-C-methyl-6-azauridine,

2′

-C-methyl-5-fluorouridine,

2′

-C-methyl-5-fluorocytidine,

2′

-C-methyl-2-chloroadenosine,

2′

-deoxy-7-deazaadenosine,

2′

-deoxy-3-deazaadenosine,

2′

-deoxy-7-deazaguanosine,

2′

-deoxy-3-deazaguanosine,

2′

-deoxy-6-azauridine,

2′

-deoxy-5-fluorouridine,

2′

-deoxy-5-fluorocytidine,

2′

-deoxy-5-iodouridine,

2′

-deoxy-5-iodocytidine,

2′

-deoxy-2-chloroadenosine,

2′

-deoxy-2-fluoroadenosine,

3′

-deoxy-7-deazaadenosine,

3′

-deoxy-7-deazaguanosine,

3′

-deoxy-3-deazaadenosine,

3′

-deoxy-3-deazaguanosine,

3′

-deoxy-6-azauridine,

3′

-deoxy-5-fluorouridine,

3′

-deoxy-5-iodouridine,

3′

-deoxy-5-fluorocytidine,

3′

-deoxy-2-chloroadenosine,

2′

,3′

-dideoxy-7-deazaadenosine,

2′

,3′

-dideoxy-7-deazaguanosine,

2′

,3′

-dideoxy-3-deazaadenosine,

2′

,3′

-dideoxy-3-deazaguanosine,

2′

,3′

-dideoxy-6-azauridine,

2′

,3′

-dideoxy-5-fluorouridine,

2′

,3′

-dideoxy-5-fluorouridine,

2′

,3′

-dideoxy-5-iodocytidine,

2′

,3′

-dideoxy-2-chloroadenosine,

2′

,3′

-dideoxy-β

-L-cytidine,

2′

,3′

-dideoxy-β

-L-adenosine,

2′

,3′

-dideoxy-β

-L-guanosine,

3′

-deoxy-β

-L-thymidine,

2′

,3′

-dideoxy-5-fluoro-β

-L-cytidine,

β

-L-thymidine,

2′

-deoxy-β

-L-cytidine,

2′

-deoxy-β

-L-adenosine,

2′

-deoxy-β

-L-guanosine,

2′

-deoxy-β

-L-inosine,

β

-L-cytidine,

β

-L-adenosine,

β

-L-guanosine,

β

-L-uridine,

β

-L-inosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-cytidine,

2′

,3′

-didehydro-3′

-dideoxy-β

-L-thymidine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-adenosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-guanosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-5-fluorocytidine,

2′

-deoxy-2′

,2′

-difluorocytidine,

9-(β

-D-arabinofuranosyl)-2-fluoroadenine,

2′

-deoxy-2′

(E)-fluoromethylenecytidine,

2′

-deoxy-2′

(Z)-fluoromethylenecytidine,

(−

)-2′

,3′

-dideoxy-3′

-thiacytidine,

(+)-2′

,3′

-dideoxy-3′

-thiacytidine,

1-β

-D-ribofuranosyl-1,2,4-triazole-3-carboxamide,

1-β

-L-ribofuranosyl-1,2,4-triazole-3-carboxamide,

1-β

-D-ribofuranosyl-1,3-imidazolium-5-olate,

1-β

-L-ribofuranosyl-1,3-imidazolium-5-olate,

1-β

-D-ribofuranosyl-5-ethynylimidazole-4-carboxamide,

1-β

-L-ribofuranosyl-5-ethynylimidazole-4-carboxamide,

1-(2-deoxy-2-fluoro-β

-D-arabinofuranosyl)-5-iodouracil,

1-(2-deoxy-2-fluoro-β

-D-arabinofuranosyl)-5-iodocytosine,

1-(2-deoxy-2-fluoro-β

-L-arabinofuranosyl)-5-methyluracil,

1-β

-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil,

E-5-(2-bromovinyl)-2′

-deoxyuridine,

5-trifluoromethylthymidine,

1-β

-D-arabinofuranosyl-5-propynyluracil,

1-(2-deoxy-2-fluoro-1-β

-D-arabinofuranosyl)-5-ethyluracil,

2′

,3′

-dideoxy-3′

-fluoroguanosine,

3′

-deoxy-3′

-fluorothymidine,

(±

)-(1α

,2β

,3α

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]adenine,

(±

)-(1α

,2β

,3α

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]guanine,

(±

)-(1β

,2α

,3β

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]guanine,

(±

)-(1β

,2α

,3β

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]adenine,

(1R,3S,4R)-9-(3-hydroxy-4-hydroxymethylcyclopent-1-yl)guanine,

(1S,2R,4R)-9-(1-hydroxy-2-hydroxymethylcyclopent-4-yl)guanine,

(2R,4R)-9-(2-hydroxymethyl-1,3-dioxolan-4-yl)-2,6-diaminopurine,

(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)cytosine,

(2R,4R)-9-(2-hydroxymethyl-1,3-dioxolan-4-yl)guanine,

(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-5-fluorocytosine,

(1R,2S,4S)-9-(4-hydroxy-3-hydroxymethyl-2-methylenecyclopent-4-yl]guanine, and

(1S,3R,4S)-9-(3-hydroxy-4-hydroxymethyl-5-methylenecyclopent-1-yl]guanine.

27. The compound defined in claim 25 of Formula (XVII):

28. The compound defined in claim 25 of Formula (XVII):

29. The compound defined in claim 27 where Nu is selected from the group consisting of:

adenosine,

cytidine,

guanosine,

uridine,

2′

-deoxyadenosine,

2′

-deoxycytidine,

2′

-deoxyguanosine,

thymidine,

inosine,

9-(β

-D-arabinofuranosyl)adenine,

1-(β

-D-arabino furanosyl)cytosine,

9-(β

-D-arabinofuranosyl)guanine,

1-(β

-D-arabinofuranosyl)uracil,

9-(β

-D-arabinofuranosyl)hypoxanthine,

1-(β

-D-arabinofuranosyl)thymine,

3′

-azido-3′

-deoxythymidine,

3′

-azido-2′

,3′

-dideoxyuridine,

3′

-azido-2′

,3′

-dideoxycytidine,

3′

-azido-2′

,3′

-dideoxyadenosine,

3′

-azido-2′

,3′

-dideoxyguanosine,

3′

-azido-2′

,3′

-dideoxyinosine,

3′

-deoxythymidine,

2′

,3′

-dideoxyuridine,

2′

,3′

-dideoxyinosine,

2′

,3′

-dideoxyadenosine,

2′

,3′

-dideoxycytidine,

2′

,3′

-dideoxyguanosine,

9-(2,3-dideoxy-1-β

-D-ribofuranosyl)-2,6-diaminopurine,

3′

-deoxy-2′

,3′

-didehydrothymidine,

2′

,3′

-didehydro-2′

,3′

-dideoxyuridine,

2′

,3′

-didehydro-2′

,3′

-dideoxycytidine,

2′

,3′

-didehydro-2′

,3′

-dideoxyadenosine,

2′

,3′

-didehydro-2′

,3′

-dideoxyguanosine,

2′

,3′

-didehydro-2′

,3′

-dideoxyinosine,

3-deazaadenosine,

3-deazaguanosine,

3-deazainosine,

7-deazaadenosine,

7-deazaguanosine,

7-deazainosine,

6-azauridine,

6-azathymidine,

6-azacytidine,

5-azacytidine,

9-(β

-D-ribofuranosyl)-6-thiopurine,

6-methylthio-9-(β

-D-ribofuranosyl)purine,

2-amino-9-(β

-D-ribofuranosyl)-6-thiopurine,

2-amino-6-methylthio-9-(β

-D-ribofuranosyl)purine,

5-fluorocytidine,

5-iodocytidine,

5-bromocytidine,

5-chlorocytidine,

5-fluorouridine,

5-iodouridine,

5-bromouridine,

5-chlorouridine,

2′

-C-methyladenosine,

2′

-C-methylcytidine,

2′

-C-methylguanosine,

2′

-C-methylinosine,

2′

-C-methyluridine,

2′

-C-methylthymidine,

2′

-deoxy-2′

-fluoroadenosine,

2′

-deoxy-2′

-fluorocytidine,

2′

-deoxy-2′

-fluoroguanosine,

2′

-deoxy-2′

-fluorouridine,

2′

-deoxy-2′

-fluoroinosine,

2′

-α

-fluorothymidine,

2′

-deoxy-2′

-fluoroarabinoadenosine,

2′

-deoxy-2′

-fluoroarabinocytidine,

2′

-deoxy-2′

-fluoroarabinoguanosine,

2′

-deoxy-2′

-fluoroarabinouridine,

2′

-deoxy-2′

-fluoroarabinoinosine,

2′

-fluorothymidine,

2′

-β

-methyladenosine,

2′

-O-methylcytidine,

2′

-O-methylguanosine,

2′

-O-methylinosine,

2′

-O-5-dimethyluridine,

2′

-C-ethynylcytidine,

2′

-C-ethynylguanosine,

2′

-C-ethynyluridine,

2′

,C-ethynylinosine,

2′

-C-ethynyl-5-methyluridine,

3′

-C-ethynyladenosine,

3′

-C-ethynylcytidine,

3′

-C-ethynylguanosine,

3′

-C-ethynyluridine,

3′

-C-ethynylinosine,

3′

-C-ethynyl-5-methyluridine,

3′

-deoxyadenosine,

3′

-deoxycytidine,

3′

-deoxyguanosine,

3′

-deoxyuridine,

3′

-deoxyinosine,

4′

-C-ethynyladenosine,

4′

-C-ethynylcytidine,

4′

-C-ethynylguanosine,

4′

-C-ethynyluridine,

4′

-C-ethynylinosine,

4′

-C-ethynylthymidine,

4′

-C-methyladenosine,

4′

-C-methylcytidine,

4′

-C-methylguanosine,

4′

-C-methyluridine,

4′

-C-methylinosine,

4′

-C-methylthymidine,

2′

-C-methyl-7-deazaadenosine,

2′

-C-methyl-7-deazaguanosine,

2′

-C-methyl-3-deazaadenosine,

2′

-C-methyl-3-deazaguanosine,

2′

-O-methyl-7-deazaadenosine,

2′

-O-methyl-7-deazaguanosine,

2′

-O-methyl-3-deazaadenosine,

2′

-O-methyl-3-deazaguanosine,

2′

-C-methyl-6-azauridine,

2′

-C-methyl-5-fluorouridine,

2′

-C-methyl-5-fluorocytidine,

2′

-C-methyl-2-chloroadenosine,

2′

-deoxy-7-deazaadenosine,

2′

-deoxy-3-deazaadenosine,

2′

-deoxy-7-deazaguanosine,

2′

-deoxy-3-deazaguanosine,

2′

-deoxy-6-azauridine,

2′

-deoxy-5-fluorouridine,

2′

-deoxy-5-fluorocytidine,

2′

-deoxy-5-iodouridine,

2′

-deoxy-5-iodocytidine,

2′

-deoxy-2-chloroadenosine,

2′

-deoxy-2-fluoroadenosine,

3′

-deoxy-7-deazaadenosine,

3′

-deoxy-7-deazaguanosine,

3′

-deoxy-3-deazaadenosine,

3′

-deoxy-3-deazaguanosine,

3′

-deoxy-6-azauridine,

3′

-deoxy-5-fluorouridine,

3′

-deoxy-5-iodouridine,

3′

-deoxy-5-fluorocytidine,

3′

-deoxy-2-chloroadenosine,

2′

,3′

-dideoxy-7-deazaadenosine,

2′

,3′

-dideoxy-7-deazaguanosine,

2′

,3′

-dideoxy-3-deazaadenosine,

2′

,3′

-dideoxy-3-deazaguanosine,

2′

,3′

-dideoxy-6-azauridine,

2′

,3′

-dideoxy-5-fluorouridine,

2′

,3′

-dideoxy-5-fluorouridine,

2′

,3′

-dideoxy-5-iodocytidine,

2′

,3′

-dideoxy-2-chloroadenosine,

2′

,3′

-dideoxy-β

-L-cytidine,

2′

,3′

-dideoxy-β

-L-adenosine,

2′

,3′

-dideoxy-β

-L-guanosine,

3′

-deoxy-β

-L-thymidine,

2′

,3′

-dideoxy-5-fluoro-β

-L-cytidine,

β

-L-thymidine,

2′

-deoxy-β

-L-cytidine,

2′

-deoxy-β

-L-adenosine,

2′

-deoxy-β

-L-guanosine,

2′

-deoxy-β

-L-inosine,

β

-L-cytidine,

β

-L-adenosine,

β

-L-guanosine,

β

-L-uridine,

β

-L-inosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-cytidine,

2′

,3′

-didehydro-3′

-dideoxy-β

-L-thymidine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-adenosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-guanosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-5-fluorocytidine,

2′

-deoxy-2′

,2′

-difluorocytidine,

9-(β

-D-arabinofuranosyl)-2-fluoroadenine,

2′

-deoxy-2′

(E)-fluoromethylenecytidine,

2′

-deoxy-2′

(Z)-fluoromethylenecytidine,

(−

)-2′

,3′

-dideoxy-3′

-thiacytidine,

(+)-2′

,3′

-dideoxy-3′

-thiacytidine,

1-β

-D-ribofuranosyl-1,2,4-triazole-3-carboxamide,

1-β

-L-ribofuranosyl-1,2,4-triazole-3-carboxamide,

1-β

-D-ribofuranosyl-1,3-imidazolium-5-olate,

1-β

-L-ribofuranosyl-1,3-imidazolium-5-olate,

1-β

-D-ribofuranosyl-5-ethynylimidazole-4-carboxamide,

1-β

-L-ribofuranosyl-5-ethynylimidazole-4-carboxamide,

1-(2-deoxy-2-fluoro-β

-D-arabinofuranosyl)-5-iodouracil,

1-(2-deoxy-2-fluoro-β

-D-arabinofuranosyl)-5-iodocytosine,

1-(2-deoxy-2-fluoro-β

-L-arabinofuranosyl)-5-methyluracil,

1-β

-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil,

E-5-(2-bromovinyl)-2′

-deoxyuridine,

5-trifluoromethylthymidine,

1-β

-D-arabinofuranosyl-5-propynyluracil,

1-(2-deoxy-2-fluoro-1-β

-D-arabinofuranosyl)-5-ethyluracil,

2′

,3′

-dideoxy-3′

-fluoroguanosine, 3′

-deoxy-3′

-fluorothymidine,

(±

)-(1α

,2β

,3α

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]adenine,

(±

)-(1α

,2β

,3α

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]guanine,

(±

)-(1β

,2α

,3β

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]guanine,

(±

)-(1β

,2α

,3β

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]adenine,

(1R,3S,4R)-9-(3-hydroxy-4-hydroxymethylcyclopent-1-yl)guanine,

(1S,2R,4R)-9-(-hydroxy-2-hydroxymethylcyclopent-4-yl)guanine,

(2R,4R)-9-(2-hydroxymethyl-1,3-dioxolan-4-yl)-2,6-diaminopurine,

(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)cytosine,

(2R,4R)-9-(2-hydroxymethyl-1,3-dioxolan-4-yl)guanine,

(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-5-fluorocytosine,

(1R,2S,4S)-9-(4-hydroxy-3-hydroxymethyl-2-methylenecyclopent-4-yl]guanine, and

(1S,3R,4S)-9-(3-hydroxy-4-hydroxymethyl-5-methylenecyclopent-1-yl]guanine.

30. The compound defined in claim 25 of Formula (XVIII):

31. The compound defined in claim 25 of Formula (XVIII):

32. The compound defined in claim 31 where Nu is selected from the group consisting of:

adenosine,

cytidine,

guanosine,

uridine,

2′

-deoxyadenosine,

2′

-deoxycytidine,

2′

-deoxyguanosine,

thymidine,

inosine,

9-(β

-D-arabinofuranosyl)adenine,

1-(β

-D-arabinofuranosyl)cytosine,

9-(β

-D-arabinofuranosyl)guanine,

1-(β

-D-arabinofuranosyl)uracil,

9-(β

-D-arabinofuranosyl)hypoxanthine,

1-(β

-D-arabinofuranosyl)thymine,

3′

-azido-3′

-deoxythymidine,

3′

-azido-2′

,3′

-dideoxyuridine,

3′

-azido-2′

,3′

-dideoxycytidine,

3′

-azido-2′

,3′

-dideoxyadenosine,

3′

-azido-2′

,3′

-dideoxyguanosine,

3′

-azido-2′

,3′

-dideoxyinosine,

3′

-deoxythymidine,

2′

,3′

-dideoxyuridine,

2′

,3′

-dideoxyinosine,

2′

,3′

-dideoxyadenosine,

2′

,3′

-dideoxycytidine,

2′

,3′

-dideoxyguanosine,

9-(2,3-dideoxy-1-β

-D-ribofuranosyl)-2,6-diaminopurine,

3′

-deoxy-2′

,3′

-didehydrothymidine,

2′

,3′

-didehydro-2′

,3′

-dideoxyuridine,

2′

,3′

-didehydro-2′

,3′

-dideoxycytidine,

2′

,3′

-didehydro-2′

,3′

-dideoxyadenosine,

2′

,3′

-didehydro-2′

,3′

-dideoxyguanosine,

2′

,3′

-didehydro-2′

,3′

-dideoxyinosine,

3-deazaadenosine,

3-deazaguanosine,

3-deazainosine,

7-deazaadenosine,

7-deazaguanosine,

7-deazainosine,

6-azauridine,

6-azathymidine,

6-azacytidine,

5-azacytidine,

9-(β

-D-ribofuranosyl)-6-thiopurine,

6-methylthio-9-(β

-D-ribofuranosyl)purine,

2-amino-9-(β

-D-ribofuranosyl)-6-thiopurine,

2-amino-6-methylthio-9-(β

-D-ribofuranosyl)purine,

5-fluorocytidine,

5-iodocytidine,

5-bromocytidine,

5-chlorocytidine,

5-fluorouridine,

5-iodouridine,

5-bromouridine,

5-chlorouridine,

2′

-C-methyladenosine,

2′

-C-methylcytidine,

2′

-C-methylguanosine,

2′

-C-methylinosine,

2′

-C-methyluridine,

2′

-C-methylthymidine,

2′

-deoxy-2′

-fluoroadenosine,

2′

-deoxy-2′

-fluorocytidine,

2′

-deoxy-2′

-fluoroguanosine,

2′

-deoxy-2′

-fluorouridine,

2′

-deoxy-2′

-fluoroinosine,

2′

-α

-fluorothymidine,

2′

-deoxy-2′

-fluoroarabinoadenosine,

2′

-deoxy-2′

-fluoroarabinocytidine,

2′

-deoxy-2′

-fluoroarabinoguanosine,

2′

-deoxy-2′

-fluoroarabinouridine,

2′

-deoxy-2′

-fluoroarabinoinosine,

2′

-β

-fluorothymidine,

2′

-O-methyladenosine,

2′

-O-methylcytidine,

2′

-O-methylguanosine,

2′

-O-methylinosine,

2′

-O-5-dimethyluridine,

2′

-C-ethynylcytidine,

2′

-C-ethynylguanosine,

2′

-C-ethynyluridine,

2′

-C-ethynylinosine,

2′

-C-ethynyl-5-methyluridine,

3′

-C-ethynyladenosine,

3′

-C-ethynylcytidine,

3′

-C-ethynylguanosine,

3′

-C-ethynyluridine,

3′

-C-ethynylinosine,

3′

-C-ethynyl-5-methyluridine,

3′

-deoxyadenosine,

3′

-deoxycytidine,

3′

-deoxyguanosine,

3′

-deoxyuridine,

3′

-deoxyinosine,

4′

-C-ethynyladenosine,

4′

-C-ethynylcytidine,

4′

-C-ethynylguanosine,

4′

-C-ethynyluridine,

4′

-C-ethynylinosine,

4′

-C-ethynylthymidine,

4′

-C-methyladenosine,

4′

-C-methylcytidine,

4′

-C-methylguanosine,

4′

-C-methyluridine,

4′

-C-methylinosine,

4′

-C-methylthymidine,

2′

-C-methyl-7-deazaadenosine,

2′

-C-methyl-7-deazaguanosine,

2′

-C-methyl-3-deazaadenosine,

2′

-C-methyl-3-deazaguanosine,

2′

-O-methyl-7-deazaadenosine,

2′

-O-methyl-7-deazaguanosine,

2′

-O-methyl-3-deazaadenosine,

2′

-O-methyl-3-deazaguanosine,

2′

-C-methyl-6-azauridine,

2′

-C-methyl-5-fluorouridine,

2′

-C-methyl-5-fluorocytidine,

2′

-C-methyl-2-chloroadenosine,

2′

-deoxy-7-deazaadenosine,

2′

-deoxy-3-deazaadenosine,

2′

-deoxy-7-deazaguanosine,

2′

-deoxy-3-deazaguanosine,

2′

-deoxy-6-azauridine,

2′

-deoxy-5-fluorouridine,

2′

-deoxy-5-fluorocytidine,

2′

-deoxy-5-iodouridine,

2′

-deoxy-5-iodocytidine,

2′

-deoxy-2-chloroadenosine,

2′

-deoxy-2-fluoroadenosine,

3′

-deoxy-7-deazaadenosine,

3′

-deoxy-7-deazaguanosine,

3′

-deoxy-3-deazaadenosine,

3′

-deoxy-3-deazaguanosine,

3′

-deoxy-6-azauridine,

3′

-deoxy-5-fluorouridine,

3′

-deoxy-5-iodouridine,

3′

-deoxy-5-fluorocytidine,

3′

-deoxy-2-chloroadenosine,

2′

,3′

-dideoxy-7-deazaadenosine,

2′

,3′

-dideoxy-7-deazaguanosine,

2′

,3′

-dideoxy-3-deazaadenosine,

2′

,3′

-dideoxy-3-deazaguanosine,

2′

,3′

-dideoxy-6-azauridine,

2′

,3′

-dideoxy-5-fluorouridine,

2′

,3′

-dideoxy-5-fluorouridine,

2′

,3′

-dideoxy-5-iodocytidine,

2′

,3′

-dideoxy-2-chloroadenosine,

2′

,3′

-dideoxy-β

-L-cytidine,

2′

,3′

-dideoxy-β

-L-adenosine,

2′

,3′

-dideoxy-β

-L-guanosine,

3′

-deoxy-β

-L-thymidine,

2′

,3′

-dideoxy-5-fluoro-β

-L-cytidine,

β

-L-thymidine,

2′

-deoxy-β

-L-cytidine,

2′

-deoxy-β

-L-adenosine,

2′

-deoxy-β

-L-guanosine,

2′

-deoxy-β

-L-inosine,

β

-L-cytidine,

β

-L-adenosine,

β

-L-guanosine,

β

-L-uridine,

β

-L-inosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-cytidine,

2′

,3′

-didehydro-3′

-dideoxy-β

-L-thymidine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-adenosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-guanosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-5-fluorocytidine,

2′

-deoxy-2′

,2′

-difluorocytidine,

9-(β

-D-arabinofuranosyl)-2-fluoroadenine,

2′

-deoxy-2′

(E)-fluoromethylenecytidine,

2′

-deoxy-2′

(Z)-fluoromethylenecytidine,

(−

)-2′

,3′

-dideoxy-3′

-thiacytidine,

(+)-2′

,3′

-dideoxy-3′

-thiacytidine,

1-β

-D-ribofuranosyl-1,2,4-triazole-3-carboxamide,

1-β

-L-ribofuranosyl-1,2,4-triazole-3-carboxamide,

1-β

-D-ribofuranosyl-1,3-imidazolium-5-olate,

1-β

-L-ribofuranosyl-1,3-imidazolium-5-olate,

1-β

-D-ribofuranosyl-5-ethynylimidazole-4-carboxamide,

1-β

-L-ribofuranosyl-5-ethynylimidazole-4-carboxamide,

1-(2-deoxy-2-fluoro-β

-D-arabinofuranosyl)-5-iodouracil,

1-(2-deoxy-2-fluoro-β

-D-arabino furanosyl)-5-iodocytosine,

1-(2-deoxy-2-fluoro-β

-L-arabinofuranosyl)-5-methyluracil,

1-β

-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil,

E-5-(2-bromovinyl)-2′

-deoxyuridine,

5-trifluoromethylthymidine,

1-β

-D-arabinofuranosyl-5-propynyluracil,

1-(2-deoxy-2-fluoro-1-β

-D-arabinofuranosyl)-5-ethyluracil,

2′

,3′

-dideoxy-3′

-fluoroguanosine,

3′

-deoxy-3′

-fluorothymidine,

(±

)-(1α

,2β

,3α

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]adenine,

(±

)-(1α

,2β

,3α

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]guanine,

(±

)-(1β

,2α

,3β

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]guanine,

(±

)-(1β

,2α

,3β

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]adenine,

(1R,3S,4R)-9-(3-hydroxy-4-hydroxymethylcyclopent-1-yl)guanine,

(1S,2R,4R)-9-(1-hydroxy-2-hydroxymethylcyclopent-4-yl)guanine,

(2R,4R)-9-(2-hydroxymethyl-1,3-dioxolan-4-yl)-2,6-diaminopurine,

(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)cytosine,

(2R,4R)-9-(2-hydroxymethyl-1,3-dioxolan-4-yl)guanine,

(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-5-fluorocytosine,

(1R,2S,4S)-9-(4-hydroxy-3-hydroxymethyl-2-methylenecyclopent-4-yl]guanine, and

(1S,3R,4S)-9-(3-hydroxy-4-hydroxymethyl-5-methylenecyclopent-1-yl]guanine.

33. The compound defined in claim 25 of Formula (XIX):

34. The compound defined in claim 25 of Formula (XIX):

35. A compound of Formula (I) which may be a D- or L-nucleotide:

36. The compound defined in claim 35 of Formula (VI):

37. The compound defined in claim 35 of Formula (VII):

38. The compound defined in claim 37

wherein X² is O;

and

wherein X⁷ is selected from the group consisting of SH, NH₂, ⁻

BH₃M⁺, alkyl, aryl, alkylamino, and arylamino.

39. The compound defined in claim 37 p1 wherein X² is O;

and

wherein X⁷ is selected from the group consisting of SH, NH₂, ⁻

BH₃M⁺, R, and NHR.

40. The compound defined in claim 35 of Formula (VIII):

41. The compound defined in claim 35 of Formula (IX):

42. The compound defined in claim 35 of Formula (X):

43. The compound defined in claim 35 of Formula (XI):

44. The compound defined in claim 35 of Formula (XII).

45. The compound defined in claim 35 of Formula (XIII):

46. The compound defined in claim 35 of Formula (XIV):

47. The compound defined in claim 35 of Formula (XV):

56. A pharmaceutical composition comprising a therapeutically effective amount of the compound according to claim 35, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable prodrug thereof, optionally in combination with one or more other active ingredients and/or with a pharmaceutically acceptable carrier

48. A compound of Formula (XVI):

49. The compound defined in claim 48 where Nu is selected from the group consisting of:

adenosine,

cytidine,

guanosine,

uridine,

2′

-deoxyadenosine,

2′

-deoxycytidine,

2′

-deoxyguanosine,

thymidine,

inosine,

9-(β

-D-arabinofuranosyl)adenine,

1-(β

-D-arabino furanosyl)cytosine,

9-(β

-D-arabinofuranosyl)guanine,

1-(β

-D-arabinofuranosyl)uracil,

9-(β

-D-arabinofuranosyl)hypoxanthine,

1-(β

-D-arabinofuranosyl)thymine,

3′

-azido-3′

-deoxythymidine,

3′

-azido-2′

,3′

-dideoxyuridine,

3′

-azido-2′

,3′

-dideoxycytidine,

3′

-azido-2′

,3′

-dideoxyadenosine,

3′

-azido-2′

,3′

-dideoxyguanosine,

3′

-azido-2′

,3′

-dideoxyinosine,

3′

-deoxythymidine,

2′

,3′

-dideoxyuridine,

2′

,3′

-dideoxyinosine,

2′

,3′

-dideoxyadenosine,

2′

,3′

-dideoxycytidine,

2′

,3′

-dideoxyguanosine,

9-(2,3-dideoxy-1-β

-D-ribofuranosyl)-2,6-diaminopurine,

3′

-deoxy-2′

,3′

-didehydrothymidine,

2′

,3′

-didehydro-2′

,3′

-dideoxyuridine,

2′

,3′

-didehydro-2′

,3′

-dideoxycytidine,

2′

,3′

-didehydro-2′

,3′

-dideoxyadenosine,

2′

,3′

-didehydro-2′

,3′

-dideoxyguanosine,

2′

,3′

-didehydro-2′

,3′

-dideoxyinosine,

3-deazaadenosine,

3-deazaguanosine,

3-deazainosine,

7-deazaadenosine,

7-deazaguanosine,

7-deazainosine,

6-azauridine,

6-azathymidine,

6-azacytidine,

5-azacytidine,

9-(β

-D-ribofuranosyl)-6-thiopurine,

6-methylthio-9-(β

-D-ribofuranosyl)purine,

2-amino-9-(β

-D-ribofuranosyl)-6-thiopurine,

2-amino-6-methylthio-9-(β

-D-ribofuranosyl)purine,

5-fluorocytidine,

5-iodocytidine,

5-bromocytidine,

5-chlorocytidine,

5-fluorouridine,

5-iodouridine,

5-bromouridine,

5-chlorouridine,

2′

-C-methyladenosine,

2′

-C-methylcytidine,

2′

-C-methylguanosine,

2′

-C-methylinosine,

2′

-C-methyluridine,

2′

-C-methylthymidine,

2′

-deoxy-2′

-fluoroadenosine,

2′

-deoxy-2′

-fluorocytidine,

2′

-deoxy-2′

-fluoroguanosine,

2′

-deoxy-2′

-fluorouridine,

2′

-deoxy-2′

-fluoroinosine,

2′

-α

-fluorothymidine,

2′

-deoxy-2′

-fluoroarabinoadenosine,

2′

-deoxy-2′

-fluoroarabinocytidine,

2′

-deoxy-2′

-fluoroarabinoguanosine,

2′

-deoxy-2′

-fluoroarabinouridine,

2′

-deoxy-2′

-fluoroarabinoinosine,

2′

-β

-fluorothymidine,

2′

-O-methyladenosine,

2′

-O-methylcytidine,

2′

-O-methylguanosine,

2′

-O-methylinosine,

2′

-O-5-dimethyluridine,

2′

-C-ethynylcytidine,

2′

-C-ethynylguanosine,

2′

-C-ethynyluridine,

2′

-C-ethynylinosine,

2′

-C-ethynyl-5-methyluridine,

3′

-C-ethynyladenosine,

3′

-C-ethynylcytidine,

3′

-C-ethynylguanosine,

3′

-C-ethynyluridine,

3′

-C-ethynylinosine,

3′

-C-ethynyl-5-methyluridine,

3′

-deoxyadenosine,

3′

-deoxycytidine,

3′

-deoxyguanosine,

3′

-deoxyuridine,

3′

-deoxyinosine,

4′

-C-ethynyladenosine,

4′

-C-ethynylcytidine,

4′

-C-ethynylguanosine,

4′

-C-ethynyluridine,

4′

-C-ethynylinosine,

4′

-C-ethynylthymidine,

4′

-C-methyladenosine,

4′

-C-methylcytidine,

4′

-C-methylguanosine,

4′

-C-methyluridine,

4′

-C-methylinosine,

4′

-C-methylthymidine,

2′

-C-methyl-7-deazaadenosine,

2′

-C-methyl-7-deazaguanosine,

2′

-C-methyl-3-deazaadenosine,

2′

-C-methyl-3-deazaguanosine,

2′

-O-methyl-7-deazaadenosine,

2′

-O-methyl-7-deazaguanosine,

2′

-O-methyl-3-deazaadenosine,

2′

-O-methyl-3-deazaguanosine,

2′

-C-methyl-6-azauridine,

2′

-C-methyl-5-fluorouridine,

2′

-C-methyl-5-fluorocytidine,

2′

-C-methyl-2-chloroadenosine,

2′

-deoxy-7-deazaadenosine,

2′

-deoxy-3-deazaadenosine,

2′

-deoxy-7-deazaguanosine,

2′

-deoxy-3-deazaguanosine,

2′

-deoxy-6-azauridine,

2′

-deoxy-5-fluorouridine,

2′

-deoxy-5-fluorocytidine,

2′

-deoxy-5-iodouridine,

2′

-deoxy-5-iodocytidine,

2′

-deoxy-2-chloroadenosine,

2′

-deoxy-2-fluoroadenosine,

3′

-deoxy-7-deazaadenosine,

3′

-deoxy-7-deazaguanosine,

3′

-deoxy-3-deazaadenosine,

3′

-deoxy-3-deazaguanosine,

3′

-deoxy-6-azauridine,

3′

-deoxy-5-fluorouridine,

3′

-deoxy-5-iodouridine,

3′

-deoxy-5-fluorocytidine,

3′

-deoxy-2-chloroadenosine,

2′

,3′

-dideoxy-7-deazaadenosine,

2′

,3′

-dideoxy-7-deazaguanosine,

2′

,3′

-dideoxy-3-deazaadenosine,

2′

,3′

-dideoxy-3-deazaguanosine,

2′

,3′

-dideoxy-6-azauridine,

2′

,3′

-dideoxy-5-fluorouridine,

2′

,3′

-dideoxy-5-fluorouridine,

2′

,3′

-dideoxy-5-iodocytidine,

2′

,3′

-dideoxy 2-chloroadenosine,

2′

,3′

-dideoxy-β

-L-cytidine,

2′

,3′

-dideoxy-β

-L-adenosine,

2′

,3′

-dideoxy-β

-L-guanosine,

3′

-deoxy-β

-L-thymidine,

2′

,3′

-dideoxy-5-fluoro-β

-L-cytidine,

β

-L-thymidine,

2′

-deoxy-β

-L-cytidine,

2′

-deoxy-β

-L-adenosine,

2′

-deoxy-β

-L-guanosine,

2′

-deoxy-β

-L-inosine,

β

-L-cytidine,

β

-L-adenosine,

β

-L-guanosine,

β

-L-uridine,

β

-L-inosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-cytidine,

2′

,3′

-didehydro-3′

-dideoxy-β

-L-thymidine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-adenosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-guanosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-5-fluorocytidine,

2′

-deoxy-2′

,2′

-difluorocytidine,

9-(β

-D-arabinofuranosyl)-2-fluoroadenine,

2′

-deoxy-2′

(E)-fluoromethylenecytidine,

2′

-deoxy-2′

(Z)-fluoromethylenecytidine,

(−

)-2′

,3′

-dideoxy-3′

-thiacytidine,

(+)-2′

,3′

-dideoxy-3′

-thiacytidine,

1-β

-D-ribofuranosyl-1,2,4-triazole-3-carboxamide,

1-β

-L-ribofuranosyl-1,2,4-triazole-3-carboxamide,

1-β

-D-ribofuranosyl-1,3-imidazolium-5-olate,

1-β

-L-ribofuranosyl-1,3-imidazolium-5-olate,

1-β

-D-ribofuranosyl-5-ethynylimidazole-4-carboxamide,

1-β

-L-ribofuranosyl-5-ethynylimidazole-4-carboxamide,

1-(2-deoxy-2-fluoro-β

-D-arabinofuranosyl)-5-iodouracil,

1-(2-deoxy-2-fluoro-β

-D-arabinofuranosyl)-5-iodocytosine,

1-(2-deoxy-2-fluoro-β

-L-arabinofuranosyl)-5-methyluracil,

1-β

-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil,

E-5-(2-bromovinyl)-2′

-deoxyuridine,

5-trifluoromethylthymidine,

1-β

-D-arabinofuranosyl-5-propynyluracil,

1-(2-deoxy-2-fluoro-1-β

-D-arabinofuranosyl)-5-ethyluracil,

2′

,3′

-dideoxy-3′

-fluoroguanosine,

3′

-deoxy-3′

-fluorothymidine,

(±

)-(1α

,2β

,3α

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]adenine,

(±

)-(1α

,2β

,3α

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]guanine,

(±

)-(1β

,2α

,3β

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]guanine,

(±

)-(1β

,2α

,3β

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]adenine,

(1R,3S,4R)-9-(3-hydroxy-4-hydroxymethylcyclopent-1-yl)guanine,

(1S,2R,4R)-9-(1-hydroxy-2-hydroxymethylcyclopent-4-yl)guanine,

(2R,4R)-9-(2-hydroxymethyl-1,3-dioxolan-4-yl)-2,6-diaminopurine,

(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)cytosine,

(2R,4R)-9-(2-hydroxymethyl-1,3-dioxolan-4-yl)guanine,

(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-5-fluorocytosine,

(1R,2S,4S)-9-(4-hydroxy-3-hydroxymethyl-2-methylenecyclopent-4-yl]guanine, and

(1S,3R,4S)-9-(3-hydroxy-4-hydroxymethyl-5-methylenecyclopent-1-yl]guanine.

50. The compound defined in claim 48 of Formula (XVII):

51. The compound defined in claim 50 where Nu is selected from the group consisting of:

adenosine,

cytidine,

guanosine,

uridine,

2′

-deoxyadenosine,

2′

-deoxycytidine,

2′

-deoxyguanosine,

thymidine,

inosine,

9-(β

-D-arabinofuranosyl)adenine,

1-(β

-D-arabinofuranosyl)cytosine,

9-(β

-D-arabinofuranosyl)guanine,

1-(β

-D-arabinofuranosyl)uracil,

9-(β

-D-arabinofuranosyl)hypoxanthine,

1-(β

-D-arabinofuranosyl)thymine,

3′

-azido-3′

-deoxythymidine,

3′

-azido-2′

,3′

-dideoxyuridine,

3′

-azido-2′

,3′

-dideoxycytidine,

3′

-azido-2′

,3′

-dideoxyadenosine,

3′

-azido-2′

,3′

-dideoxyguanosine,

3′

-azido-2′

,3′

-dideoxyinosine,

3′

-deoxythymidine,

2′

,3′

-dideoxyuridine,

2′

,3′

-dideoxyinosine,

2′

,3′

-dideoxyadenosine,

2′

,3′

-dideoxycytidine,

2′

,3′

-dideoxyguanosine,

9-(2,3-dideoxy-1-β

-D-ribofuranosyl)-2,6-diaminopurine,

3′

-deoxy-2′

,3′

-didehydrothymidine,

2′

,3′

-didehydro-2′

,3′

-dideoxyuridine,

2′

,3′

-didehydro-2′

,3′

-dideoxycytidine,

2′

,3′

-didehydro-2′

,3′

-dideoxyadenosine,

2′

,3′

-didehydro-2′

,3′

-dideoxyguanosine,

2′

,3′

-didehydro-2′

,3′

-dideoxyinosine,

3-deazaadenosine,

3-deazaguanosine,

3-deazainosine,

7-deazaadenosine,

7-deazaguanosine,

7-deazainosine,

6-azauridine,

6-azathymidine,

6-azacytidine,

5-azacytidine,

9-(β

-D-ribofuranosyl)-6-thiopurine,

6-methylthio-9-(β

-D-ribofuranosyl)purine,

2-amino-9-(β

-D-ribofuranosyl)-6-thiopurine,

2-amino-6-methylthio-9-(β

-D-ribo furanosyl)purine,

5-fluorocytidine,

5-iodocytidine,

5-bromocytidine,

5-chlorocytidine,

5-fluorouridine,

5-iodouridine,

5-bromouridine,

5-chlorouridine,

2′

-C-methyladenosine,

2′

-C-methylcytidine,

2′

-C-methyl guano sine,

2′

-C-methylinosine,

2′

-C-methyluridine,

2′

-C-methylthymidine,

2′

-deoxy-2′

-fluoroadenosine,

2′

-deoxy-2′

-fluorocytidine,

2′

-deoxy-2′

-fluoroguanosine,

2′

-deoxy-2′

-fluorouridine,

2′

-deoxy-2′

-fluoroinosine,

2′

-(α

-fluorothymidine,

2′

-deoxy-2′

-fluoroarabinoadenosine,

2′

-deoxy-2′

-fluoroarabinocytidine,

2′

-deoxy-2′

-fluoroarabinoguanosine,

2′

-deoxy-2′

-fluoroarabinouridine,

2′

-deoxy-2′

-fluoroarabinoinosine,

2′

-β

-fluorothymidine,

2′

-O-methyladenosine,

2′

-O-methylcytidine,

2′

-O-methylguanosine,

2′

-O-methylinosine,

2′

-O-5-dimethyluridine,

2′

-C-ethynylcytidine,

2′

-C-ethynylguanosine,

2′

-C-ethynyluridine,

2′

-C-ethynylinosine,

2′

-C-ethynyl-5-methyluridine,

3′

-C-ethynyladenosine,

3′

-C-ethynylcytidine,

3′

-C-ethynylguanosine,

3′

-C-ethynyluridine,

3′

-C-ethynylinosine,

3′

-C-ethynyl-5-methyluridine,

3′

-deoxyadenosine,

3′

-deoxycytidine,

3′

-deoxyguanosine,

3′

-deoxyuridine,

3′

-deoxyinosine,

4′

-C-ethynyladenosine,

4′

-C-ethynylcytidine,

4′

-C-ethynylguanosine,

4′

-C-ethynyluridine,

4′

-C-ethynylinosine,

4′

-C-ethynylthymidine,

4′

-C-methyladenosine,

4′

-C-methylcytidine,

4′

-C-methylguanosine,

4′

-C-methyluridine,

4′

-C-methylinosine,

4′

-C-methylthymidine,

2′

-C-methyl-7-deazaadenosine,

2′

-C-methyl-7-deazaguanosine,

2′

-C-methyl-3-deazaadenosine,

2′

-C-methyl-3-deazaguanosine,

2′

-O-methyl-7-deazaadenosine,

2′

-O-methyl-7-deazaguanosine,

2′

-O-methyl-3-deazaadenosine,

2′

-O-methyl-3-deazaguanosine,

2′

-C-methyl-6-azauridine,

2′

-C-methyl-5-fluorouridine,

2′

-C-methyl-5-fluorocytidine,

2′

-C-methyl-2-chloroadenosine,

2′

-deoxy-7-deazaadenosine,

2′

-deoxy-3-deazaadenosine,

2′

-deoxy-7-deazaguanosine,

2′

-deoxy-3-deazaguanosine,

2′

-deoxy-6-azauridine,

2′

-deoxy-5-fluorouridine,

2′

-deoxy-5-fluorocytidine,

2′

-deoxy-5-iodouridine,

2′

-deoxy-5-iodocytidine,

2′

-deoxy-2-chloroadenosine,

2′

-deoxy-2-fluoroadenosine,

3′

-deoxy-7-deazaadenosine,

3′

-deoxy-7-deazaguanosine,

3′

-deoxy-3-deazaadenosine,

3′

-deoxy-3-deazaguanosine,

3′

-deoxy-6-azauridine,

3′

-deoxy-5-fluorouridine,

3′

-deoxy-5-iodouridine,

3′

-deoxy-5-fluorocytidine,

3′

-deoxy-2-chloroadenosine,

2′

,3′

-dideoxy-7-deazaadenosine,

2′

,3′

-dideoxy-7-deazaguanosine,

2′

,3′

-dideoxy-3-deazaadenosine,

2′

,3′

-dideoxy-3-deazaguanosine,

2′

,3′

-dideoxy-6-azauridine,

2′

,3′

-dideoxy-5-fluorouridine,

2′

,3′

-dideoxy-5-fluorouridine,

2′

,3′

-dideoxy-5-iodocytidine,

2′

,3′

-dideoxy-2-chloroadenosine,

2′

,3′

-dideoxy-β

-L-cytidine,

2′

,3′

-dideoxy-β

-L-adenosine,

2′

,3′

-dideoxy-β

-L-guanosine,

3′

-deoxy-β

-L-thymidine,

2′

,3′

-dideoxy-5-fluoro-β

-L-cytidine,

β

-L-thymidine,

2′

-deoxy-β

-L-cytidine,

2′

-deoxy-β

-L-adenosine,

2′

-deoxy-β

-L-guanosine,

2′

-deoxy-β

-L-inosine,

β

-L-cytidine,

β

-L-adenosine,

β

-L-guanosine,

β

-L-uridine,

β

-L-inosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-cytidine,

2′

,3′

-didehydro-3′

-dideoxy-β

-L-thymidine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-adenosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-guanosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-5-fluorocytidine,

2′

-deoxy-2′

,2′

-difluorocytidine,

9-(β

-D-arabinofuranosyl)-2-fluoroadenine,

2′

-deoxy-2′

(E)-fluoromethylenecytidine,

2′

-deoxy-2′

(Z)-fluoromethylenecytidine,

(−

)-2′

,3′

-dideoxy-3′

-thiacytidine,

(+)-2′

,3′

-dideoxy-3′

-thiacytidine,

1-β

-D-ribofuranosyl-1,2,4-triazole-3-carboxamide,

1-O-L-ribofuranosyl-1,2,4-triazole-3-carboxamide,

1-β

-D-ribofuranosyl-1,3-imidazolium-5-olate,

1-β

-L-ribofuranosyl-1,3-imidazolium-5-olate,

1-β

-D-ribofuranosyl-5-ethynylimidazole-4-carboxamide,

1-β

-L-ribofuranosyl-5-ethynylimidazole-4-carboxamide,

1-(2-deoxy-2-fluoro-β

-D-arabinofuranosyl)-5-iodouracil,

1-(2-deoxy-2-fluoro-β

-D-arabinofuranosyl)-5-iodocytosine,

1-(2-deoxy-2-fluoro-β

-L-arabinofuranosyl)-5-methyluracil,

1-β

-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil,

E-5-(2-bromovinyl)-2′

-deoxyuridine,

5-trifluoromethylthymidine,

1-β

-D-arabinofuranosyl-5-propynyluracil,

1-(2-deoxy-2-fluoro-1-β

-D-arabinofuranosyl)-5-ethyluracil,

2′

,3′

-dideoxy-3′

-fluoroguanosine,

3′

-deoxy-3′

-fluorothymidine,

(±

)-(1α

,2β

,3α

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]adenine,

(±

)-(1α

,2β

,3α

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]guanine,

(±

)-(1β

,2α

,3β

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]guanine,

(±

)-(1β

,2α

,3β

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]adenine,

(1R,3S,4R)-9-(3-hydroxy-4-hydroxymethylcyclopent-1-yl)guanine,

(1S,2R,4R)-9-(1-hydroxy-2-hydroxymethylcyclopent-4-yl)guanine,

(2R,4R)-9-(2-hydroxymethyl-1,3-dioxolan-4-yl)-2,6-diaminopurine,

(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)cytosine,

(2R,4R)-9-(2-hydroxymethyl-1,3-dioxolan-4-yl)guanine,

(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-5-fluorocytosine,

(1R,2S,4S)-9-(4-hydroxy-3-hydroxymethyl-2-methylenecyclopent-4-yl]guanine, and

(1S,3R,4S)-9-(3-hydroxy-4-hydroxymethyl-5-methylenecyclopent-1-yl]guanine.

52. The compound defined in claim 48 of Formula (XVIII):

53. The compound defined in claim 52 where Nu is selected from the group consisting of:

adenosine,

cytidine,

guanosine,

uridine,

2′

-deoxyadenosine,

2′

-deoxycytidine,

2′

-deoxyguanosine,

thymidine,

inosine,

9-(β

-D-arabinofuranosyl)adenine,

1-(β

-D-arabinofuranosyl)cytosine,

9-(β

-D-arabinofuranosyl)guanine,

1-(β

-D-arabinofuranosyl)uracil,

9-(β

-D-arabinofuranosyl)hypoxanthine,

1-(β

-D-arabinofuranosyl)thymine,

3′

-azido-3′

-deoxythymidine,

3′

-azido-2′

,3′

-dideoxyuridine,

3′

-azido-2′

,3′

-dideoxycytidine,

3′

-azido-2′

,3′

-dideoxyadenosine,

3′

-azido-2′

,3-dideoxyguanosine,

3′

-azido-2′

,3′

-dideoxyinosine,

3′

-deoxythymidine,

2′

,3′

-dideoxyuridine,

2′

,3′

-dideoxyinosine,

2′

,3′

-dideoxyadenosine,

2′

,3′

-dideoxycytidine,

2′

,3′

-dideoxyguanosine,

9-(2,3-dideoxy-1-β

-D-ribofuranosyl)-2,6-diaminopurine,

3′

-deoxy-2′

,3′

-didehydrothymidine,

2′

,3′

-didehydro-2′

,3′

-dideoxyuridine,

2′

,3′

-didehydro-2′

,3′

-dideoxycytidine,

2′

,3′

-didehydro-2′

,3′

-dideoxyadenosine,

2′

,3′

-didehydro-2′

,3′

-dideoxyguanosine,

2′

,3′

-didehydro-2′

,3′

-dideoxyinosine,

3-deazaadenosine,

3-deazaguanosine,

3-deazainosine,

7-deazaadenosine,

7-deazaguanosine,

7-deazainosine,

6-azauridine,

6-azathymidine,

6-azacytidine,

5-azacytidine,

9-(β

-D-ribofuranosyl)-6-thiopurine,

6-methylthio-9-(β

-D-ribofuranosyl)purine,

2-amino-9-(β

-D-ribofuranosyl)-6-thiopurine,

2-amino-6-methylthio-9-(β

-D-ribofuranosyl)purine,

5-fluorocytidine,

5-iodocytidine,

5-bromocytidine,

5-chlorocytidine,

5-fluorouridine,

5-iodouridine,

5-bromouridine,

5-chlorouridine,

2′

-C-methyladenosine,

2′

-C-methylcytidine,

2′

-C-methylguanosine,

2′

-C-methylinosine,

2′

-C-methyluridine,

2′

-C-methylthymidine,

2′

-deoxy-2′

-fluoroadenosine,

2′

-deoxy-2′

-fluorocytidine,

2′

-deoxy-2′

-fluoroguanosine,

2′

-deoxy-2′

-fluorouridine,

2′

-deoxy-2′

-fluoroinosine,

2′

-α

-fluorothymidine,

2′

-deoxy-2′

-fluoroarabinoadenosine,

2′

-deoxy-2′

-fluoroarabinocytidine,

2′

-deoxy-2′

-fluoroarabinoguanosine,

2′

-deoxy-2′

-fluoroarabinouridine,

2′

-deoxy-2′

-fluoroarabinoinosine,

2′

-β

-fluorothymidine,

2′

-O-methyladenosine,

2′

-O-methylcytidine,

2′

-O-methylguanosine,

2′

-O-methylinosine,

2′

-O-5-dimethyluridine,

2′

-C-ethynylcytidine,

2′

-C-ethynylguanosine,

2′

-C-ethynyluridine,

2′

-C-ethynylinosine,

2′

-C-ethynyl-5-methyluridine,

3-C-ethynyladenosine,

3′

-C-ethynylcytidine,

3′

-C-ethynylguanosine,

3′

-C-ethynyluridine,

3′

-C-ethynylinosine,

3-C-ethynyl-5-methyluridine,

3′

-deoxyadenosine,

3′

-deoxycytidine,

3′

-deoxyguanosine,

3′

-deoxyuridine,

3′

-deoxyinosine,

4′

-C-ethynyladenosine,

4′

-C-ethynylcytidine,

4′

-C-ethynylguanosine,

4′

-C-ethynyluridine,

4′

-C-ethynylinosine,

4′

-C-ethynylthymidine,

4′

-C-methyladenosine,

4′

-C-methylcytidine,

4′

-C-methylguanosine,

4′

-C-methyluridine,

4′

-C-methylinosine,

4′

-C-methylthymidine,

2′

-C-methyl-7-deazaadenosine,

2′

-C-methyl-7-deazaguanosine,

2′

-C-methyl-3-deazaadenosine,

2′

-C-methyl-3-deazaguanosine,

2′

-O-methyl-7-deazaadenosine,

2′

-O-methyl-7-deazaguanosine,

2′

-O-methyl-3-deazaadenosine,

2′

-O-methyl-3-deazaguanosine,

2′

-C-methyl-6-azauridine,

2′

-C-methyl-5-fluorouridine,

2′

-C-methyl-5-fluorocytidine,

2′

-C-methyl-2-chloroadenosine,

2′

-deoxy-7-deazaadenosine,

2′

-deoxy-3-deazaadenosine,

2′

-deoxy-7-deazaguanosine,

2′

-deoxy-3-deazaguanosine,

2′

-deoxy-6-azauridine,

2′

-deoxy-5-fluorouridine,

2′

-deoxy-5-fluorocytidine,

2′

-deoxy-5-iodouridine,

2′

-deoxy-5-iodocytidine,

2′

-deoxy-2-chloroadenosine,

2′

-deoxy-2-fluoroadenosine,

3-deoxy-7-deazaadenosine,

3-deoxy-7-deazaguanosine,

3′

-deoxy-3-deazaadenosine,

3′

-deoxy-3-deazaguanosine,

3′

-deoxy-6-azauridine,

3′

-deoxy-5-fluorouridine,

3′

-deoxy-5-iodouridine,

3′

-deoxy-5-fluorocytidine,

3-deoxy-2-chloroadenosine,

2′

,3′

-dideoxy-7-deazaadenosine,

2′

,3′

-dideoxy-7-deazaguanosine,

2′

,3′

-dideoxy-3-deazaadenosine,

2′

,3′

-dideoxy-3-deazaguanosine,

2′

,3′

-dideoxy-6-azauridine,

2′

,3′

-dideoxy-5-fluorouridine,

2′

,3′

-dideoxy-5-fluorouridine,

2′

,3′

-dideoxy-5-iodocytidine,

2′

,3′

-dideoxy-2-chloroadenosine,

2′

,3′

-dideoxy-β

-L-cytidine,

2′

,3′

-dideoxy-β

-L-adenosine,

2′

,3′

-dideoxy-β

-L-guanosine,

3′

-deoxy-β

-L-thymidine,

2′

,3′

-dideoxy-5-fluoro-β

-L-cytidine,

β

-L-thymidine,

2′

-deoxy-β

-L-cytidine,

2′

-deoxy-β

-L-adenosine,

2′

-deoxy-β

-L-guanosine,

2′

-deoxy-β

-L-inosine,

β

-L-cytidine,

β

-L-adenosine,

β

-L-guanosine,

β

-L-uridine,

β

-L-inosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-cytidine,

2′

,3′

-didehydro-3′

-dideoxy-β

-L-thymidine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-adenosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-guanosine,

2′

,3′

-didehydro-2′

,3′

-dideoxy-β

-L-5-fluoro cytidine,

2′

-deoxy-2′

,2′

-difluorocytidine,

9-(D-D-arabinofuranosyl)-2-fluoroadenine,

2′

-deoxy-2′

(E)-fluoromethylenecytidine,

2′

-deoxy-2′

(Z)-fluoromethylenecytidine,

(−

)-2′

,3′

-dideoxy-3′

-thiacytidine,

(+)-2′

,3′

-dideoxy-3′

-thiacytidine,

1-β

-D-ribofuranosyl-1,2,4-triazole-3-carboxamide,

1-β

-L-ribofuranosyl-1,2,4-triazole-3-carboxamide,

1-β

-D-ribofuranosyl-1,3-imidazolium-5-olate,

1-β

-L-ribofuranosyl-1,3-imidazolium-5-olate,

1-β

-D-ribofuranosyl-5-ethynylimidazole-4-carboxamide,

1-β

-L-ribofuranosyl-5-ethynylimidazole-4-carboxamide,

1-(2-deoxy-2-fluoro-β

-D-arabinofuranosyl)-5-iodouracil,

1-(2-deoxy-2-fluoro-β

-D-arabinofuranosyl)-5-iodocytosine,

1-(2-deoxy-2-fluoro-β

-L-arabinofuranosyl)-5-methyluracil,

1-β

-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil,

E-5-(2-bromovinyl)-2′

-deoxyuridine,

5-trifluoromethylthymidine,

1-β

-D-arabinofuranosyl-5-propynyluracil,

1-(2-deoxy-2-fluoro-1-O-D-arabinofuranosyl)-5-ethyluracil,

2′

,3′

-dideoxy-3′

-fluoroguanosine,

3′

-deoxy-3′

-fluorothymidine,

(±

)-(1α

,2β

,3α

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]adenine,

(±

)-(1α

,2β

,3α

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]guanine,

(±

)-(1β

,2α

,3β

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]guanine,

(±

)-(1β

,2α

,3β

)-9-[2,3-bis(hydroxymethyl)-1-cyclobutyl]adenine,

(1R,3S,4R)-9-(3-hydroxy-4-hydroxymethylcyclopent-1-yl)guanine,

(1S,2R,4R)-9-(-hydroxy-2-hydroxymethylcyclopent-4-yl)guanine,

(2R,4R)-9-(2-hydroxymethyl-1,3-dioxolan-4-yl)-2,6-diaminopurine,

(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)cytosine,

(2R,4R)-9-(2-hydroxymethyl-1,3-dioxolan-4-yl)guanine,

(2R,4R)-1-(2-hydroxymethyl-1,3-dioxolan-4-yl)-5-fluorocytosine,

(1R,2S,4S)-9-(4-hydroxy-3-hydroxymethyl-2-methylenecyclopent-4-yl]guanine, and

(1S,3R,4S)-9-(3-hydroxy-4-hydroxymethyl-5-methylenecyclopent-1-yl]guanine.

54. The compound defined in claim 48 Formula (XIX):