Nucleoside compounds for treating viral infections

• US 7,202,223 B2
• Filed: 06/04/2004
• Issued: 04/10/2007
• Est. Priority Date: 10/27/2003
• Status: Expired due to Fees

• Current Assignee: Smithkline Beecham Corporation (GlaxoSmithKline PLC)
• Original Assignee: Genelabs Technologies, Inc. (GlaxoSmithKline PLC)
• Inventors: Roberts, Christopher D., Keicher, Jesse D.
• Primary Examiner(s): CRANE, LAWRENCE E
• Application Number:
  US10/861,090
• Publication Number:
  US 20060079468A1
• Time in Patent Office: 1,040 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: 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 are as defined herein.

Claims

1. A compound of formula Ia:

3. A pharmaceutical composition comprising a pharmaceutically acceptable diluent and a therapeutically effective amount of a compound according to any one of claims 1 to and 2.

4. A method for treating hepatitis C virus (HCV) in a mammalian patient suffering from HCV which method comprises administering to said mammal a pharmaceutical composition according to claim 3.

2. A compound selected from the group consisting of:

7-(2′

-C-methyl-β

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

7-(2′

-C-methyl-β

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

7-(2′

-C-methyl-5′

-monophospho-β

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

7-(2′

-C-methyl-5′

-diphospho-β

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

7-(2′

-C-methyl-5′

-triphospho-β

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

7-(2′

-C-methyl-5′

-monophospho-β

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

7-(2′

-C-methyl-5′

-diphospho-β

-D-ribofuranosyl)-4-amino-5-(2-cis-methoxy-ethen-1-yl)-pyrrolo[2,3-d]pyrimidine; and

7-(2′

-C-methyl-5′

-triphospho-β

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

or pharmaceutically acceptable salts or partial salts thereof.

5. A compound of formula II:

7. A pharmaceutical composition comprising a pharmaceutically acceptable diluent and a therapeutically effective amount of a compound according to any one of claims 5 and 6.

8. method for treating hepatitis C virus (HCV) in a mammalian patient suffering from HCV which method comprises administering to said mammal a pharmaceutical composition according to claim 7.

6. A compound selected from the group consisting of:

7-(2′

-C-methyl-β

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

7-(2′

-C-methyl-5′

-phospho-β

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

7-(2′

-C-methyl-5′

-diphospho-β

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

7-(2′

-C-methyl-5′

-triphospho-β

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

or pharmaceutically acceptable salts or partial salts thereof.

9. A compound of formula III:

10. A compound selected from the group consisting of:

7-(2′

-C-methyl-β

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

7-(2′

-C-methyl-β

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

7-(2′

-C-methyl-5′

-phospho-β

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

7-(2′

-C-methyl-5′

-phospho-β

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

7-(2′

-C-methyl-5′

-diphospho-β

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

7-(2′

-C-methyl-5′

-diphospho-β

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

7-(2′

-C-methyl-5′

-triphospho-β

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

7-(2′

-C-methyl-5′

-triphospho-β

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

or pharmaceutically acceptable salts or partial salts thereof.

11. A pharmaceutical composition comprising a pharmaceutically acceptable diluent and a therapeutically effective amount of a compound according to any one of claims 9 and 10.

12. A method for treating hepatitis C virus (HCV) in a mammalian patient suffering from HCV which method comprises administering to said mammal a pharmaceutical composition according to claim 11.

13. A compound of formula V:

15. A pharmaceutical composition comprising a pharmaceutically acceptable diluent and a therapeutically effective amount of a compound according to any one of claims 13 and 14.

16. A method for treating hepatitis C virus (HCV) in a mammalian patient suffering from HCV which method comprises administering to said mammal a pharmaceutical composition according to claim 15.

14. A compound selected from the group consisting of:

7-(2′

-C-methyl-β

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

7-(2′

-C-methyl-β

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

7-(2′

-C-methyl-β

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

7-(2′

-C-methyl-5′

-phospho-β

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

7-(2′

-C-methyl-5′

-phospho-β

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

7-(2′

-C-methyl-5′

-phospho-β

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

7-(2′

-C-methyl-5′

-diphospho-β

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

7-(2′

-C-methyl-5′

-diphospho-β

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

7-(2′

-C-methyl-5′

-diphosphol-β

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

7-(2′

-C-methyl-5′

-triphosphol-β

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

7-(2′

-C-methyl-5′

-triphosphol-β

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

7-(2′

-C-methyl-5′

-triphosphol-β

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

or pharmaceutically acceptable salts or partial salts thereof.

17. 7-(2′

-C-methyl-β

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

20. 7-(2′

-C-methyl-β

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

21. 7-(2′

-C-methyl-β

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

22. 7-(2′

-C-methyl-β

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

23. 7-(2′

-C-methyl-β

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

24. 7-(2′

-C-methyl-β

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