Highly active nucleoside derivative for the treatment of HCV

• US 9,447,132 B2
• Filed: 04/14/2014
• Issued: 09/20/2016
• Est. Priority Date: 04/12/2013
• Status: Expired due to Fees

• Current Assignee: Achillion Pharmaceuticals, Inc. (Astrazeneca PLC)
• Original Assignee: Achillion Pharmaceuticals, Inc. (Astrazeneca PLC)
• Inventors: Deshpande, Milind, Wiles, Jason Allan, Hashimoto, Akihiro, Phadke, Avinash
• Primary Examiner(s): Crane, Lawrence E
• Application Number:
  US14/252,290
• Publication Number:
  US 20140309189A1
• Time in Patent Office: 890 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• 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 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07B 59/005 Sugars; Derivatives thereof; Nucleosides; Nucleotides; Nucleic acids
• CPC Class Codes: C07F 9/2429 of arylalkanols
• CPC Class Codes: C07F 9/2458 of aliphatic amines
• CPC Class Codes: C07F 9/58 Pyridine rings
• CPC Class Codes: C07H 1/00 Processes for the preparation of sugar derivatives
• CPC Class Codes: C07H 19/067 with ribosyl as the saccharide radical
• 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

A deuterated nucleoside analog of the formula

• • and the pharmaceutically acceptable salts thereof are provided by this disclosure. The disclosure also includes pharmaceutical compositions comprising a compound or salt of the formula and a carrier. Compounds and salts of this formula are useful for treating viral infections, including HCV infections. A method for treating a host afflicted with hepatitis C or other disorders is also presented that includes administering an effective treatment amount of a nucleoside or nucleotide that has deuterium with at least 50% enrichment at the 5′-position of the nucleoside or nucleotide.

Claims

1. A compound of Formula I or a pharmaceutically acceptable salt thereof, wherein Formula I is

2. A compound or salt of claim 1 of the formula

3. A compound or salt of claim 2 of the formula

4. A compound or salt of claim 2 of the formula

5. A compound or salt of claim 2, wherein each position represented as D has deuterium enrichment of at least 90%.

6. A compound of salt of claim 2, wherein each position represented as D has deuterium enrichment of at least 95%.

7. A 50/50 mixture of stereoisomers of the compound of claim 2, wherein the mixture is

8. A pharmaceutical composition comprising an active agent, wherein the active agent is a compound or salt of claim 2, and also comprising a pharmaceutically acceptable carrier.

9. The pharmaceutical composition of claim 8, further comprising at least one additional active agent(s).

10. The pharmaceutical composition of claim 9, wherein the at least one additional active agent(s) are an HCV NS3 protease inhibitor, an HCV NS5A inhibitor, an HCV NS5B inhibitor, or a combination of the foregoing.

11. The pharmaceutical composition of claim 9, wherein the at least one additional active agents is an NS5A inhibitor and at least one of sovaprevir.

12. A method of treating an HCV infection in a patient in need thereof, comprising administering a therapeutically effective amount of a compound or salt of claim 2 to the patient in need thereof.

13. A method of treating an HCV infection in a patient in need thereof, comprising administering a therapeutically effective amount of a pharmaceutical composition of claim 8 to the patient in need thereof.