Nucleoside compounds for treating viral infections

• US 7,144,868 B2
• Filed: 06/04/2004
• Issued: 12/05/2006
• Est. Priority Date: 10/27/2003
• Status: Expired due to Fees

• Current Assignee: Smithkline Beecham Corporation (GSK plc)
• Original Assignee: Genelabs Technologies, Inc. (GSK plc)
• Inventors: Roberts, Christopher D., Keicher, Jesse D.
• Primary Examiner(s): CRANE, LAWRENCE E
• Application Number:
  US10/861,311
• Publication Number:
  US 20050090463A1
• Time in Patent Office: 914 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 31/14 for RNA viruses
• CPC Class Codes: C07H 19/00 Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof

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, each of R, Y, W, W¹ and W² is as defined herein.

Claims

1. A compound of formula I:

10. A compound according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8 and 9 wherein R is selected from the group consisting of —

C(O)NH₂, —

Si(CH₃)₃, pyrid-2-yl, 4-methoxyphenyl, and —

CH(OCH₂CH₃)₂.

20. A pharmaceutical composition comprising a pharmaceutically acceptable diluent and a therapeutically effective amount of a compound according to any one of claims 1, 2, 3, 4, 5, 6, 7, 8, 9 or 11–

19.

21. A method for treating hepatitis C virus (HCV) in a mammalian patient in need thereof suffering from HCV which method comprises administering to said mammal a pharmaceutical composition according to claim 20.

2. A compound represented by Formula II:

3. A compound represented by Formula III:

4. A compound represented by Formula IV:

5. A compound represented by Formula V:

6. A compound represented by Formula VI:

7. A compound represented by formula VII:

8. A compound represented by Formula VIII:

9. A compound represented by Formula IX:

11. A compound selected from the group consisting of:

7-(2′

-C-methyl-β

-D-ribofuranosyl)-4-amino-5-(2′

-trimethylsilylethyn-1-yl)-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-β

-D-ribofuranosyl)-4-amino-5-[2-(pyrid-2-yl)ethyn-1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-β

-D-ribofuranosyl)-4-amino-5-[2-(pyrid-4-yl)ethyn-1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-β

-D-ribofuranosyl)-4-amino-5-(2-(4-methoxyphenyl)-ethyn-1-yl)-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-β

-D-ribofuranosyl)-4-amino-5-(2-carboxamidoethyn-1-yl)-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-β

-D-ribofuranosyl)-4-amino-5[(3,3-diethoxy)proparg-1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-β

-D-ribofuranosyl)-4-amino-5[(N,N-dimethyl-2-carboxamido)ethyn-1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-β

-D-ribofuranosyl)-4-amino-5[(N-amino-2-carboxamido)ethyn-1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-phospho-β

-D-ribofuranosyl)-4-amino-5-(2′

-trimethylsilylethyn-1-yl) -pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-phospho-β

-D-ribofuranosyl)-4-amino-5-[2-(pyrid-2-yl)ethyn-1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-phospho-β

-D-ribofuranosyl)-4-amino-5-[2-(pyrid-4-yl)ethyn-1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-phospho-β

-D-ribofuranosyl)-4-amino-5-(2-(4-methoxyphenyl)ethyn-1-yl) -pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-phospho-β

-D-ribofuranosyl)-4-amino-5-(2-carboxamidoethyn-1-yl) -pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-phospho-β

-D-ribofuranosyl)-4-amino-5-[(3,3-diethoxy)proparg-1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-phospho-β

-D-ribofuranosyl)-4-amino-5-[2-(N,N -dimethylcarboxyamido)ethyn-1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-phospho-β

-D-ribofuranosyl)-4-amino-5-[2-(N-aminocarboxyamido)ethyn -1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-diphospho-β

-D-ribofuranosyl)-4-amino-5-(2′

-trimethylsilylethyn-1-yl) -pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-diphospho-β

-D-ribofuranosyl)-4-amino-5-[2-(pyrid-2-yl)ethyn-1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-diphospho-β

-D-ribofuranosyl)-4-amino-5-[2-(pyrid-4-yl)ethyn-1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-diphospho-β

-D-ribofuranosyl)-4-amino-5-(2-(4-methoxyphenyl)ethyn-1-yl)-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-diphospho-β

-D-ribofuranosyl)-4-amino-5-(2-carboxyamidoethyn-1-yl) -pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-diphospho-β

-D-ribofuranosyl)-4-amino-5[(3,3-diethoxy)proparg-1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-diphospho-β

-D-ribofuranosyl)-4-amino-[(N,N-dimethyl-2-carboxyamido)ethyn-1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-diphospho-β

-D-ribofuranosyl)-4-amino-5[(N-amino-2-carboxyamido)ethyn-1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-triphospho-β

-D-ribofuranosyl)-4-amino-5-(2′

-trimethylsilylethyn-1-yl) -pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-triphospho-β

-D-ribofuranosyl)-4-amino-5-[2-(pyrid-2-yl)ethyn-1-yl) -pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-triphospho-β

-D-ribofuranosyl)-4-amino-[2-(pyrid-4-yl)ethyn-1-yl) -pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-triphospho-β

-D-ribofuranosyl)-4-amino-5-(2-(4-methoxyphenyl)ethyn-1-yl) -pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-triphospho-β

-D-ribofuranosyl)-4-amino-5-(2-carboxyamidoethyn-1-yl) -pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-triphospho-β

-D-ribofuranosyl)-4-amino-5[(3,3-diethoxy)proparg-1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-triphospho-β

-D-ribofuranosyl)-4-amino-5[(N,N -dimethylcarboxylamido)ethyn-1-yl]-pyrrolo[2,3-d]pyrimidine; and

7-(2′

-C-methyl-5′

-triphospho-β

-D-ribofuranosyl)-4-amino-5[(N-aminocarboxylamido)ethyn-1-yl]-pyrrolo[2,3-d]pyrimidine;

or pharmaceutically acceptable salts or partial salts thereof.

12. 7-(2′

-C-methyl-β

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

13. 7-(2′

-C-methyl-β

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

14. 7-(2′

-C-methyl-β

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

15. 7-(2′

-C-methyl-β

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

16. 7-(2′

-C-methyl-β

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

17. 7-(2′

-C-methyl-β

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

18. 7-(2′

-C-methyl-β

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

19. 7-(2′

-C-methyl-β

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