NOVEL TRICYCLIC NUCLEOSIDES OR NUCLEOTIDES AS THERAPEUTIC AGENTS

• US 20100311684A1
• Filed: 05/10/2010
• Published: 12/09/2010
• Est. Priority Date: 08/27/2003
• Status: Abandoned Application

• Current Assignee: Biota Scientific Management Pty Limited (Vaxart, Inc.)
• Original Assignee: Biota Scientific Management Pty Limited (Vaxart, Inc.)
• Inventors: Lambert, John, Sakthivel, Kandasamy, Ewing, Deborah K., Jin, Yi, Cook, Phillip Dan, Prhavc, Marija, Rajwanshi, Vivek K., Ewing, Gregory, Rajappan, Vasanthankumar
• Application Number:
  US12/776,691
• Publication Number:
  US 20100311684A1
• Time in Patent Office: Days
• US Class Current: 514/49
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 19/23 Heterocyclic radicals containing two or more heterocyclic rings condensed among themselves or condensed with a common carbocyclic ring system, not provided for in groups C07H19/14 - C07H19/22

Abstract

Nucleosides and nucleotides containing a tricyclic base portion thereof are useful for treating infectious diseases and proliferative disorders, such as viral infections or cancer respectively.

Claims

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

2. The compound of claim 1 wherein Z⁴ is a participant in a π

bond, and base B is;

3. The compound of claim 2 wherein G is H, F, Cl, Br, I, R, OR, SR, NH₂, NHR or NR₂, and R is alkyl.

4. The compound of claim 2 wherein X is NH or NR, and base B is selected from:

5. The compound of claim 2 wherein X is N and base B is:

6. The compound of claim 1 wherein Z⁴ is not a participant in a π

bond, and base B is selected from;

7. The compound of claim 6 wherein X is NH or NR, and base B is selected from:

8. The compound of claim 7 wherein X is NH, and base B is selected from:

9. The compound of claim 6 wherein X is NH or NR, and base B is selected from:

10. The compound of claim 6 wherein X is N, and base B is selected from:

11. The compound of claim 1 wherein the base B is selected from one of the following structures:

12. The compound of claims 1 wherein the nucleotide or nucleoside has the structure:

13. The compound of claim 12 wherein R¹, R³ and R⁴ are hydrogen.

14. The compound of claim 13 wherein R², R²′

and R³′

are independently H, F, Cl, Br, I, OH, N₃, CN, R or OR, and R is alkyl.

15. The compound of claim 13 wherein R²′

and R³′

are OH.

16. The compound of claim 15 wherein R² is H or methyl.

17. The compound of claim 1 wherein R⁵ is OH, monophosphate, or a monophosphonate thereof.

18. A method for treating a viral infection comprising administering a therapeutically effective amount of a compound of claim 1 to a mammal in need thereof.

19. The method of claim 18, wherein the compound is administered in combination with one or more active anti-viral agents.