Nucleoside phosphoramidates

• US 8,633,309 B2
• Filed: 01/10/2013
• Issued: 01/21/2014
• Est. Priority Date: 05/20/2009
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Pharmasset LLC (Gilead Sciences Inc.)
• Inventors: Ross, Bruce, Sofia, Michael Joseph, Pamulapati, Ganapati Reddy, Rachakonda, Suguna, Zhang, Hai-Ren, Chun, Byoung-Kwon, Wang, Peiyuan
• Primary Examiner(s): OLSON, ERIC
• Application Number:
  US13/738,425
• Publication Number:
  US 20130137654A1
• Time in Patent Office: 376 Days
• Field of Search: None
• US Class Current: 536/28.53
• CPC Class Codes: A61K 31/664 Amides of phosphorus acids
• CPC Class Codes: A61K 31/7072 having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
• CPC Class Codes: A61K 31/716 Glucans
• CPC Class Codes: A61K 45/00 Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61P 3/12 for electrolyte homeostasis
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• 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: C07F 9/24 Esteramides
• CPC Class Codes: C07F 9/242 of hydroxyaryl compounds
• CPC Class Codes: C07F 9/65586 at least one of the hetero rings does not contain nitrogen as ring hetero atom
• CPC Class Codes: C07H 1/00 Processes for the preparation of sugar derivatives
• CPC Class Codes: C07H 17/02 Heterocyclic radicals containing only nitrogen as ring hetero atoms
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• 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
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

Disclosed herein are nucleoside phosphoramidates and their use as agents for treating viral diseases. These compounds are inhibitors of RNA-dependent 5 RNA viral replication and are useful as inhibitors of HCV NS5B polymerase, as inhibitors of HCV replication and for treatment of hepatitis C infection in mammals.

Claims

1. A compound represented by the formula (4):

2. The compound according to claim 1, wherein the compound is at least 98% of the S_Pstereoisomer represented by the formula (S_P-4) and not more than 2% of the R_Pstereoisomer represented by the formula (R_P-4).

3. The compound according to claim 1, wherein the compound is at least 99% of the S_Pstereoisomer represented by the formula (S_P-4) and not more than 1% of the R_Pstereoisomer represented by the formula (R_P-4).

4. A pharmaceutical composition comprising the compound according to claim 1 and a pharmaceutically acceptable medium.

5. A pharmaceutical composition comprising the compound according to claim 2 and a pharmaceutically acceptable medium.

6. A pharmaceutical composition comprising the compound according to claim 3 and a pharmaceutically acceptable medium.

7. A method of treating a hepatitis C virus infection in a human comprising administering to the human an effective amount of the compound according to claim 1.

8. The method according to claim 7 further comprising administering to the human another antiviral agent.

9. A method of treating a hepatitis C virus infection in a human comprising administering to the human an effective amount of the compound according to claim 2.

10. The method according to claim 9 further comprising administering to the human another antiviral agent.

11. A method of treating a hepatitis C virus infection in a human comprising administering to the human an effective amount of the compound according to claim 3.

12. The method according to claim 11 further comprising administering to the human another antiviral agent.