Nucleosides with antiviral and anticancer activity

• US 8,815,830 B2
• Filed: 03/28/2014
• Issued: 08/26/2014
• Est. Priority Date: 12/09/2004
• Status: Active Grant

• Current Assignee: Regents of The University of Minnesota (University of Minnesota)
• Original Assignee: Regents of The University of Minnesota (University of Minnesota)
• Inventors: Wagner, Carston R.
• Primary Examiner(s): LEWIS, PATRICK T
• Application Number:
  US14/229,292
• Publication Number:
  US 20140213543A1
• Time in Patent Office: 151 Days
• Field of Search: None
• US Class Current: 514/51
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07F 9/6561 containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
• CPC Class Codes: C07F 9/65616 containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
• CPC Class Codes: C07H 1/00 Processes for the preparation of sugar derivatives
• CPC Class Codes: C07H 19/052 Imidazole radicals
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/16 Purine radicals
• CPC Class Codes: C07H 19/167 with ribosyl as the saccharide radical
• CPC Class Codes: C07H 19/19 with arabinosyl as the saccharide radical
• CPC Class Codes: C07H 19/20 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/207 the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine adenine dinucleotide or nicotinamide-adenine dinucleotide
• 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
• CPC Class Codes: C07K 2/00 Peptides of undefined number of amino acids; Derivatives thereof
• CPC Class Codes: C07K 4/00 Peptides having up to 20 amino acids in an undefined or only partially defined sequence; Derivatives thereof

Abstract

The invention provides a compound of formula (I), wherein R₁-R₆ and X have any of the values described, as well as pharmaceutical compositions comprising such compounds and therapeutic methods comprising the administration of such compounds.

Claims

1. A compound of formula I:

2. The compound or salt of claim 1 wherein R₁ is guanine, cytosine, thymine, 3-deazaadenine, or uracil.

3. The compound or salt of claim 1 wherein R₁ is cytosine, thymine, 3-deazaadenine, or uracil.

4. The compound or salt of claim 1 wherein R₁ is cytosine, thymine, or uracil.

5. The compound or salt of claim 1 wherein R₁ is a nitrogen linked radical of formula VI:

6. The compound or salt of claim 1 wherein R₂ is fluoro.

7. The compound or salt of claim 1 wherein R₅ is a nitrogen linked radical of formula III:

8. The compound or salt of claim 7 wherein R_h is hydrogen, (C₁-C₆)alkyl, phenylmethyl, or 3-indolylmethyl.

9. The compound or salt of claim 8 wherein R_j is H or (C₁-C₆)alkyl.

10. The compound or salt of claim 8 wherein the carbon bearing R_h has the (R) absolute configuration.

11. The compound or salt of claim 1 wherein R₅ is a (C₁-C₆)alkyl ester of L-alanine.

12. The compound or salt of claim 11 wherein R₇ is hydrogen.

13. A method for treating a viral infection in an animal comprising administering to an animal in need of such treatment an effective amount of a compound or salt of formula I according to claim 1.

14. The method of claim 13 wherein R₁ is guanine, cytosine, thymine, 3-deazaadenine, or uracil.

15. The method of claim 13 wherein R₁ is cytosine, thymine, 3-deazaadenine, or uracil.

16. The method of claim 13 wherein R₁ is cytosine, thymine, or uracil.

17. The method of claim 13 wherein R₁ is a nitrogen linked radical of formula VI:

18. The method of claim 13 wherein R₂ is fluoro.

19. The method of claim 13 wherein R₅ is a nitrogen linked radical of formula III:

20. The method of claim 19 wherein R_h is hydrogen, (C₁-C₆)alkyl, phenylmethyl, or 3-indolylmethyl.

21. The method of claim 20 wherein R_j is H or (C₁-C₆)alkyl.

22. The method of claim 20 wherein the carbon bearing R_h has the (R) absolute configuration.

23. The method of claim 13 wherein R₅ is a (C₁-C₆)alkyl ester of L-alanine.

24. The method of claim 23 wherein R₇ is hydrogen.

25. The method of claim 13 wherein the viral infection is caused by HCV.

26. The method of claim 13 wherein the animal is a human.

27. The method of claim 26 wherein the compound or salt of formula I is orally administered.

28. A pharmaceutical composition comprising a compound or salt of formula I as described in claim 1 and a pharmaceutically acceptable vehicle or carrier.