Antiviral nucleosides

• US 7,754,699 B2
• Filed: 12/08/2006
• Issued: 07/13/2010
• Est. Priority Date: 12/09/2005
• Status: Active Grant

• Current Assignee: Gilead Pharmasset LLC (Gilead Sciences Inc.), Roche Palo Alto LLC (Roche Holding AG)
• Original Assignee: Roche Palo Alto LLC (Roche Holding AG)
• Inventors: Sarma, Keshab, Clark, Jeremy, Wang, Peiyuan, Chun, Byoung-Kwon
• Primary Examiner(s): McIntosh, III; Traviss C
• Application Number:
  US11/635,898
• Publication Number:
  US 20070197463A1
• Time in Patent Office: 1,313 Days
• Field of Search: None
• US Class Current: 514/49
• 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: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/12 Triazine radicals
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Compounds having the formula I wherein R¹ is as herein defined are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for inhibiting hepatitis replication, and processes for making the compounds of formula I

Claims

1. A compound of formula I

2. A compound according to claim 1 wherein R¹ is ethyl, n-propyl, iso-propyl, n-butyl or iso-butyl.

3. A compound according to claim 2 wherein R¹ is ethyl or iso-propyl.

4. A compound according to claim 3 wherein R¹ is iso-propyl and the compound is the hydrochloride or sulfate salt.

5. A compound according to claim 1 wherein R¹ is ethoxy, n-propyloxy or iso-propyloxy.

6. A method for treating a disease mediated by the Hepatitis C Virus (HCV) virus comprising administering to a mammal in need thereof, a therapeutically effective quantity of a compound according to claim 1.

7. The method of claim 6 wherein the compound a dose of between 0.1 and 10 g per day is administered to the patient.

8. A method according to claim 7 wherein a dose of between 0.5 and 7.5 g per day is administered to the patient.

9. A method according to claim 7 wherein a dose of between 1.0 and 6.0 g per day is administered to the patient.

10. The method of claim 6 further comprising administering at least one immune system modulator and/or at least one antiviral agent that inhibits replication of HCV.

11. The method of claim 10 wherein the immune system modulator is an interferon, interleukin, tumor necrosis factor or colony stimulating factor.

12. The method of claim 11 wherein the immune system modulator is an interferon or chemically derivatized interferon.

13. The method of claim 10 further comprising administering at least one other antiviral agent.

14. The method of claim 13 where the antiviral compound is selected from the group consisting of an HCV protease inhibitor, another nucleoside HCV polymerase inhibitor, a non-nucleoside HCV polymerase inhibitor, an HCV helicase inhibitor, an HCV primase inhibitor and an HCV fusion inhibitor.

15. A pharmaceutical composition comprising a therapeutically effective quantity of a compound according to claim 1 admixed with at least one pharmaceutically acceptable carrier, diluent or excipient.

16. A process for the selective O-acylation of a nucleoside II to afford an O-acyl nucleoside I under basic reaction conditions