Nucleoside compounds for treating viral infections

• US 20050215511A1
• Filed: 10/21/2004
• Published: 09/29/2005
• Est. Priority Date: 10/27/2003
• Status: Active Grant

• 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.
• Granted Patent: US 7,244,713 B2
• Time in Patent Office: Days
• US Class Current: 514/45
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• 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: 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.

Claims

1. A compound of Formula I:

2. The compound according to claim 1, wherein each of W, W¹, and W² is independently hydrogen or a pharmaceutically acceptable prodrug selected from the group consisting of acyl, oxyacyl, phosphonate, phosphate esters, phosphate, phosphonamidate, phosphorodiamidate, phosphoramidate monoester, cyclic phosphoramidate, cyclic phosphorodiamidate, phosphoramidate diester, and —

C(O)CHR³°

NH₂ where R³⁰ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, and a sidechain of an amino acid.

3. The compound according to claim 2 wherein W is H.

4. The compound according to claim 2 wherein W¹ is H.

5. The compound according to claim 2 wherein W² is H.

6. The compound according to claim 2 wherein W and W¹ are H.

7. The compound according to claim 2 wherein W and W² are H.

8. The compound according to claim 2 wherein W¹ and W² are H.

9. The compound according to claim 2 wherein W, W¹ and W² are H.

10. The compound of claim 2 wherein W¹ and W² are hydrogen and W is represented by the formula:

11. The compound of claim 2 wherein W and W² are hydrogen and W¹ is represented by the formula:

12. A compound according to any of claims 1 to 11 wherein T is —

C≡

C—

R and R is selected from the group consisting of tri(C₁-C₄)alkylsilyl, —

C(O)NR¹R², alkoxyalkyl, heteroaryl, substituted heteroaryl, phenyl and phenyl substituted with 1 to 3 substituents selected from the group consisting of alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, alkoxy, substituted alkoxy, acyl, acylamino, acyloxy, aminoacyl, amidino, amino, substituted amino, carboxyl, carboxyl ester, cyano, cycloalkyl, substituted cycloalkyl, cycloalkoxy, substituted cycloalkoxy, guanidino, halo, heteroaryl, substituted heteroaryl, hydrazino, hydroxyl, nitro, thiol, and —

S(O)_mR³;

where R¹ and R² are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, amino, substituted amino, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic and substituted heterocyclic provided that only one of R¹ and R² is amino or substituted amino, and further wherein R¹ and R², together with the nitrogen atom pendant thereto, form a heterocyclic or substituted heterocyclic;

R³ is selected from the group consisting of alkyl, substituted alkyl, amino, substituted amino, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic and substituted heterocyclic; and

m is an integer equal to 0, 1 or 2;

or a pharmaceutically acceptable salt thereof.

13. A compound according to claim 12 wherein R is selected from the group consisting of —

C(O)NH₂, —

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

CH(OCH₂CH₃)₂.

14. A compound according to any of claims 1 to 11 wherein T is —

C≡

C—

R and R is —

C(O)OH.

15. A compound according to any of claims 1 to 11 wherein T is —

C≡

C—

R, R is —

C(O)OR¹⁴, and R¹⁴ is alkyl.

16. A compound according to claim 15 wherein R¹⁴ is methyl, or ethyl.

17. A compound according to any of claims 1 to 11 wherein T is —

CH═

CH-Q², where Q² is selected from hydrogen or cis-methoxy.

18. A compound according to any of claims 1 to 11 wherein T is —

C(═

O)H.

19. A compound according to any of claims 1 to 11 wherein T is —

CH═

NNHR¹⁵ where R¹⁵ is independently selected from the group consisting of hydrogen and alkyl.

20. A compound according to any of claims 1 to 11 wherein T is —

CH═

N(OR¹⁵) where R¹⁵ is independently selected from the group consisting of hydrogen and alkyl.

21. A compound according to any of claims 1 to 11 wherein T is —

CH(OR¹⁶)₂ where R¹⁶ is independently (C₃-C₆)alkyl.

22. A compound according to any of claims 1 to 11 wherein T is —

B(OR¹⁵)₂, where R¹⁵ is independently selected from the group consisting of hydrogen and alkyl.

45. A pharmaceutical composition comprising a pharmaceutically acceptable diluent and a therapeutically effective amount of a compound of any of claims 1 to 11 or 23 to 44 or a mixture of two or more of such compounds.

46. A method for treating a viral infection in a mammal mediated at least in part by a virus in the flaviviridae family of viruses which method comprises administering to a mammal, that has been diagnosed with said viral infection or is at risk of developing said viral infection, a pharmaceutical composition according to claim 45.

47. The method according to claim 46, wherein said virus is hepatitis C virus.

48. The method of claim 47 in combination with the administration of a therapeutically effective amount of one or more agents active against HCV.

49. The method of claim 48 wherein said active agent against is Ribavirin, levovirin, viramidine, thymosin alpha-1, an inhibitor of NS3 serine protease, and inhibitor of inosine monophosphate dehydrogenase, interferon-alpha, pegylated interferon-alpha, alone or in combination with Ribavirin or levovirin.

50. The method of claim 49 wherein said agent active against HCV is interferon-alpha or pegylated interferon-alpha alone or in combination with Ribavirin or levovirin.

23. 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-1-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-dimethylcarboxamido)ethyn-1-yl]-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-phospho-β

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

7-(2′

-C-methyl-5′

-diphospho-β

-D-ribofuranosyl)-4-amino-5-[(N-amino-2-carboxamido)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-5-[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-carboxamidoethyn-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;

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;

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;

7-(2′

-C-methyl-5′

-triphospho-β

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

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′

-diphospho-β

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

7-(2′

-C-methyl-5′

-triphospho-β

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

7-(2′

-C-methyl-5′

-triphospho-β

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

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′

-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-(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;

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′

-triphospho-β

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

7-(2′

-C-methyl-β

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

7-(2′

-C-methyl-5′

-phospho-β

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

7-(2′

-C-methyl-5′

-diphospho-β

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

7-(2′

-C-methyl-5′

-triphospho-β

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

7-(2′

-methyl-β

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

7-(2′

-C-methyl-5′

-phospho-β

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

7-(2′

-C-methyl-5′

-diphospho-β

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

7-(2′

-C-methyl-5′

-triphospho-β

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

7-(2′

-C-methyl-β

-D-ribofuranosyl)-4-amino-5-(carbaldehyde oxime)-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-phospho-β

-D-ribofuranosyl)-4-amino-5-(carbaldehyde oxime)-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-diphospho-β

-D-ribofuranosyl)-4-amino-5-(carbaldehyde oxime)-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-triphospho-β

-D-ribofuranosyl)-4-amino-5-(carbaldehyde oxime)-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-β

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

7-(2′

-C-methyl-5′

-phospho-β

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

7-(2′

-C-methyl-5′

-diphospho-β

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

7-(2′

-C-methyl-5′

-triphospho-β

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

7-(2′

-C-methyl-β

-D-ribofuranosyl)-4-amino-5-(boronic acid)-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-phospho-β

-D-ribofuranosyl)-4-amino-5-(boronic acid)-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-diphospho-β

-D-ribofuranosyl)-4-amino-5-(boronic acid)-pyrrolo[2,3-d]pyrimidine;

7-(2′

-C-methyl-5′

-triphospho-β

-D-ribofuranosyl)-4-amino-5-(boronic acid)-pyrrolo[2,3-d]pyrimidine;

and pharmaceutically acceptable salts or partial salts thereof.

24. 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.

25. 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.

26. 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.

27. 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.

28. 7-(2′

-C-methyl-β

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

29. 7-(2′

-C-methyl-β

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

30. 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.

31. 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.

32. 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.

33. 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.

34. 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.

35. 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.

36. 7-(2′

-C-methyl-β

-D-ribofuranosyl)-4-amino-5-(2-(4-fluorophenyl)ethyn-β

-yl)-pyrrolo[2,3-d]pyrimidine or a pharmaceutically acceptable salt or partial salt thereof.

37. 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.

38. 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.

39. 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.

40. 7-(2′

-C-methyl-β

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

41. 7-(2′

-methyl-β

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

42. 7-(2′

-C-methyl-β

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

43. 7-(2′

-C-methyl-β

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

44. 7-(2′

-C-methyl-β

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