Tricyclic nucleosides or nucleotides as therapeutic agents

• US 7,268,119 B2
• Filed: 02/14/2007
• Issued: 09/11/2007
• Est. Priority Date: 08/27/2003
• Status: Expired due to Fees

• Current Assignee: Biota Scientific Management Pty Limited (Vaxart, Inc.)
• Original Assignee: Biota Scientific Management Pty Limited (Vaxart, Inc.)
• Inventors: Jin, Yi, Cook, Phillip Dan, Lambert, John, Prhavc, Marija, Rajwanshi, Vivek K., Ewing, legal representative, Sakthivel, Kandasamy, Rajappan, Vasanthankumar, Ewing, deceased
• Primary Examiner(s): Jiang; Shaojia Anna
• Assistant Examiner(s): Olson; Eric S
• Application Number:
  US11/674,954
• Publication Number:
  US 20070135363A1
• Time in Patent Office: 209 Days
• Field of Search: 536/28.7 514/43,52,28.7
• US Class Current: 514/43
• 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 pharmaceutical composition comprising a therapeutically effective amount of at least one compound of the formula (I) which may be a D- or L-nucleotide or nucleoside in combination with a pharmaceutically acceptable carrier:

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

bond, and base B is;

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

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

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

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

bond, and base B is selected from;

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

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

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

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

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

12. The pharmaceutical composition of claim 1 wherein the nucleotide or nucleoside has the structure

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

14. The pharmaceutical composition of claim 13 wherein R², R^2′

and R^3′

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

15. The pharmaceutical composition of claim 13 wherein R^2′

and R^3′

are OH.

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

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

18. The pharmaceutical composition of claim 1, wherein the compound is selected from one of the following structures:

19. A method for treating a viral infection comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 1 to a mammal in need thereof, wherein the viral infection is HBV or HCV.