Nucleoside phosphoramidate prodrugs

• US 9,585,906 B2
• Filed: 03/12/2015
• Issued: 03/07/2017
• Est. Priority Date: 03/30/2007
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Pharmasset LLC (Gilead Sciences Inc.)
• Inventors: Du, Jinfa, Nagarathnam, Dhanapalan, Sofia, Michael J., Wang, Peiyuan
• Primary Examiner(s): LEWIS, PATRICK T
• Application Number:
  US14/656,546
• Publication Number:
  US 20150231166A1
• Time in Patent Office: 726 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/706 containing six-membered rings with nitrogen as a ring hetero atom
• CPC Class Codes: A61K 31/7064 containing condensed or non-condensed pyrimidines
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• 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 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: C07H 17/02 Heterocyclic radicals containing only nitrogen as ring hetero atoms
• CPC Class Codes: C07H 19/04 Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/073 with 2-deoxyribosyl as the saccharide radical
• CPC Class Codes: C07H 19/10 with the saccharide radical esterified by phosphoric or polyphosphoric acids
• CPC Class Codes: C07H 19/20 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

Abstract

Disclosed herein are phosphoramidate prodrugs of nucleoside derivatives for the treatment of viral infections in mammals, which is a compound, its stereoisomer, salt (acid or basic addition salt), hydrate, solvate, or crystalline form thereof, represented by the following structure:

Also disclosed are methods of treatment, uses, and processes for preparing each of which utilize the compound represented by formula I.

Claims

1. A compound represented by the following formula:

2. The compound of claim 1, having the following structure:

3. The compound of claim 1, having the following structure:

4. The compound of claim 1, having the following structure:

5. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable excipient.

6. A method of treating HCV comprising administering a therapeutically effective amount of a compound according to claim 1 to a human subject in need thereof.

7. The method of claim 6 further comprising administering to the human subject a therapeutically effective amount of a second antiviral agent.

8. The method of claim 7 wherein the second antiviral agent is an NS5A inhibitor.

9. The method of claim 7 wherein the second antiviral agent is an NS3 protease inhibitor.

10. The method of claim 6 further comprising administering to the human subject therapeutically effective amounts of an NS5A inhibitor and an NS3 protease inhibitor.