Nucleoside compounds for treating viral infections

• US 7,157,434 B2
• Filed: 10/20/2004
• Issued: 01/02/2007
• Est. Priority Date: 10/27/2003
• Status: Expired due to Fees

• Current Assignee: Smithkline Beecham Corporation (Smithkline Beecham PLC)
• Original Assignee: Genelabs Technologies, Inc. (GlaxoSmithKline PLC)
• Inventors: Roberts, Christopher D., Dyatkina, Natalia B., Keicher, Jesse D.
• Primary Examiner(s): Crane; L. E.
• Application Number:
  US10/970,321
• Publication Number:
  US 20050107312A1
• Time in Patent Office: 804 Days
• Field of Search: 514/43, 536/26.23, 536/26.26, 536/26.7, 536/27.2
• US Class Current: 514/43
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07H 19/14 Pyrrolo-pyrimidine radicals

Abstract

Disclosed are compounds, compositions and methods for treating viral infections caused by a flaviviridae family virus, such as hepatitis C virus. Such compounds are represented by Formula I as follows:

wherein, Y, W, W¹ and W² are as defined herein.

Claims

1. A compounds of Formula I:

2. The compound of claim 1 wherein Y is oxygen.

3. The compound of claim 1 wherein W is hydrogen, or W¹ is hydrogen, or W² is hydrogen.

4. The compound of claim 1 wherein W and W¹ are hydrogen, or W and W² are hydrogen, or W¹ and W² are hydrogen.

5. The compound of claim 1 wherein W, W¹ and W² are hydrogen.

6. The compound of claim 4 wherein W¹ and W² are hydrogen and W is hydrogen, acyl, oxyacyl, phosphonate, phosphate ester, phosphate, phosphonamidate, phosphorodiamidate, phosphoramidate monoester, cyclic phosphoramidate, cyclic phosphorodiamidate, phosphoramidate diester, and —

C(O)CHR²NH₂ where R² is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroaryl, substituted hetereoaryl, heterocyclyl, substituted heterocyclyl, and a sidechain of an amino acid.

7. The compound of claim 6 wherein W¹ and W² are hydrogen and W is represented by the formula:

8. The compound of claim 4 wherein W and W² are hydrogen and W¹ is represented by the formula:

18. A pharmaceutical composition comprising a pharmaceutically acceptable diluent and a therapeutically effective amount of a compound as defined in any one of claims 1, 2, 3 to 9 and 10 to 17.

19. A method for treating and/or inhibiting a viral infection in a mammal in need thereof which infection is mediated at least in part by hepatitis C virus which method comprise administering to said mammal, that has been diagnosed with said viral infection or is at risk of developing said viral infection, a pharmaceutical composition according to claim 18.

9. A compound of Formula II:

10. The compound of claim 9 wherein W is represented by the formula:

11. 7-(2′

-C-methyl-β

-D-ribofuranosyl)-4-amino-5-(ethyn-1-yl)-pyrrolo[2,3-d]pyrimidine or pharmaceutically acceptable salts or partial salts thereof.

12. 7-(2′

-C-methyl-5′

-phospho-β

-D-ribofuranosyl)-4-amino-5-(ethyn-1-yl)-pyrrolo[2,3-d]pyrimidine or pharmaceutically acceptable salts or partial salts thereof.

13. 7-(2′

-C-methyl-5′

-diphospho-β

-D-ribofuranosyl)-4-amino-5-[ethyn-1-yl]-pyrrolo[2,3-d]pyrimidine or pharmaceutically acceptable salts or partial salts thereof.

14. 7-(2′

-C-methyl-5′

-triphospho-β

-D-ribofuranosyl)-4-amino-5-(ethyn-1-yl)-pyrrolo[2,3-d]pyrimidine or pharmaceutically acceptable salts or partial salts thereof.

15. 7-(2′

-methyl-5′

-(phenoxy-L-alaninyl)phosphate-β

-D-ribofuranosyl)-4-amino-5-(ethyn-1-yl)-pyrrolo[2,3-d]pyrimidine or pharmaceutically acceptable salts or partial salts thereof.

16. 7-(2′

-methyl-3′

-O-L-valine ester-β

-D-ribofuranosyl)-4-amino-5-(ethyn-1-yl)-pyrrolo[2,3-d]pyrimidine or pharmaceutically acceptable salts or partial salts thereof.

17. 7-(2′

-methyl-3′

-O-L-alanine ester-β

-D-ribofuranosyl)-4-amino-5-(ethyn-1-yl)-pyrrolo[2,3-d]pyrimidine or pharmaceutically acceptable salts or partial salts thereof.