Nucleoside derivatives for treating hepatitis C virus infection

• US 20060258613A1
• Filed: 07/24/2006
• Published: 11/16/2006
• Est. Priority Date: 09/30/2002
• Status: Active Grant

• Current Assignee: Smithkline Beecham Corporation (GlaxoSmithKline PLC)
• Original Assignee: Genelabs Technologies, Inc. (GlaxoSmithKline PLC)
• Inventors: Roberts, Christopher D., Dyatkina, Natalia B., Keicher, Jesse
• Granted Patent: US 7,432,248 B2
• Time in Patent Office: Days
• US Class Current: 514/45
• CPC Class Codes: A61P 31/12 Antivirals
• 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
• CPC Class Codes: C07H 19/167 with ribosyl as the saccharide radical

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 below:

2. A compound of claim 1 wherein, W is selected from the group consisting of hydrogen, monophosphate, diphosphate, and triphosphate.

3. A compound of claim 1 wherein, W¹ and W² are independently hydrogen or acyl.

4. A compound of claim 3, wherein one of W¹ and W² is an acyl group selected from the group consisting of acetyl, trimethylacetyl, and acyl groups derived from amino acids.

7. A compound of claim 1 or claim 5, wherein, Z is selected from the group consisting of acyl, nitro, halo, cyano, —

C(═

NR²)R³, acetylenyl and substituted acetylenyl of the formula —

C≡

C—

R⁴ where R², R³ and R⁴ are as defined above.

8. A compound of claim 7 wherein, Z is selected from formyl, nitro, bromro, iodo, and —

C≡

C—

R⁴ and R⁴ is selected from H, phenyl, and —

Si(CH₃)₃.

10. A pharmaceutical compositions comprising a pharmaceutically acceptable diluent and a therapeutically effective amount of a compound of any one of claims 1, 5 and 9.

11. A method for treating a viral infection mediated at least in part by a virus in the flaviviridae family of viruses in mammals which methods comprise administering to a mammal, that has been diagnosed with said viral infection or is at risk of developing said viral infection, a pharmaceutical composition comprising a pharmaceutically acceptable diluent and a therapeutically effective amount of a compound of any one of claims 1, 5 and 9.

12. The method of claim 11, wherein said virus is HCV.

5. A compound of Formula II

6. A compound of claim 5 wherein, W is selected from the group consisting of hydrogen, monophosphate, diphosphate, and triphosphate.

9. A compound selected from the group consisting of:

1-(6-hydroxylamino-7-ethynyl-7-deazapurin-9-yl)-2-methyl-β

-D-ribofuranose (1);

1-(6-hydroxylamino-7-(2-phenylethyn-1-yl)-7-deazapurin-9-yl)-2-methyl-β

-D-ribofuranose (2);

1-(6-hydroxylamino-7-(2-(pyridin-2-yl)-ethyn-1-yl)-7-deazapurin-9-yl)-2-methyl-β

-D-ribofuranose (3);

1-(6-hydroxylamino-7-(2-(4-fluorophenyl)ethyn-1-yl)-7-deazapurin-9-yl)-2-methyl-β

-D-ribofuranose (4);

1-(6-hydroxylamino-7-(2-(4-methylphenyl)ethyn-1-yl)-7-deaza-purin-9-yl)-2-methyl-β

-D-ribofuranose (5);

1-(6-hydroxylamino-7-(2-carboxylethyn-1-yl)-7-deazapurin-9-yl)-2-methyl-β

-D-ribofuranose (6);

1-(6-hydroxylamino-7-(2-ethyl carboxylethyn-1-yl)-7-deazapurin-9-yl)-2-methyl-β

-D-ribofuranose (7);

1-(6-hydroxylamino-7-(2-carboxamidoethyn-1-yl)-7-deazapurin-9-yl)-2-methyl-β

-D-ribofuranose (8);

1-(6-hydroxylamino-7-(2-trimethylsilylethyn-1-yl)-7-deazapurin-9-yl)-2-methyl-β

-D-ribofuranose (9);

1-(6-hydroxylamino-7-ethenyl-7-deaza-purin-9-yl)-2-methyl-β

-D-ribofuranose (10);

1-(6-hydroxylamino-7-formyl-7-deaza-purin-9-yl)-2-methyl-β

-D-ribofuranose (11);

1-(6-hydroxylamino-7-(carbaldehyde oxime))-7-deazapurin-9-yl)-2-methyl-β

-D-ribofuranose (12);

1-(6-hydroxylamino-7-(boronic acid)-7-deazapurin-9-yl)-2-methyl-β

-D-ribofuranose (13);

1-(6-hydroxylamino-7-(2,2-difluorovinyl)-7-deazapurin-9-yl)-2-methyl-β

-D-ribofuranose (14);

1-(6-hydroxylamino-7-(2-cis-methoxyvinyl)-7-deazapurin-9-yl)-2-methy-β

-D-ribofuranose (15);

1-(6-hydroxylamino-7-nitro-7-deaza-purin-9-yl)-2-methyl-β

-D-ribofuranose (16);

1-(6-hydroxylamino-7-cyano-7-deaza-purin-9-yl)-2-methyl-β

-D-ribofuranose (17);

1-(6-methoxyamino-7-ethynyl-7-deazapurin-9-yl)-2-methyl-β

-D-ribofuranose (18);

1-(6-methoxyamino-7-nitro-7-deaza-purin-9-yl)-2-methyl-β

-D-ribofuranose (19);

1-(6-methoxyamino-7-formyl-7-deaza-purin-9-yl)-2-methyl-β

-D-ribofuranose (20);

and pharmaceutically acceptable salts thereof.