Antiviral compounds

• US 9,156,823 B2
• Filed: 11/16/2011
• Issued: 10/13/2015
• Est. Priority Date: 11/17/2010
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: Gilead Pharmasset LLC (Gilead Sciences Inc.)
• Inventors: Bacon, Elizabeth M., Cottell, Jeromy J., Katana, Ashley Anne, Kato, Darryl, Krygowski, Evan S., Link, John O., Taylor, James, Tran, Chinh Viet, Martin, Teresa Alejandra Trejo, Yang, Zheng-Yu, Zipfel, Sheila
• Primary Examiner(s): Shibuya, Mark
• Assistant Examiner(s): Shiao, Yih-Horng
• Application Number:
  US13/884,578
• Publication Number:
  US 20140018313A1
• Time in Patent Office: 1,427 Days
• Field of Search: 514/43, 514/232.8, 514/394, 544/139, 548/300.7, 548/302.1
• 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 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/4184 condensed with carbocyclic rings, e.g. benzimidazoles
• CPC Class Codes: A61K 31/4188 condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• 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 31/00 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 31/18 for HIV
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 403/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: C07D 471/08 Bridged systems
• CPC Class Codes: C07D 491/10 Spiro-condensed systems
• CPC Class Codes: C07D 491/107 with only one oxygen atom as ring hetero atom in the oxygen-containing ring
• CPC Class Codes: C07D 491/113 with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
• CPC Class Codes: C07D 493/04 Ortho-condensed systems
• CPC Class Codes: C07D 495/04 : Ortho-condensed systems
• CPC Class Codes: C07D 513/04 : Ortho-condensed systems

Abstract

The invention is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

Claims

1. A compound of formula (I):

E^1a-V^1a—

C(═

O)—

P^1a—

W^1a—

P^1b—

C(═

O)—

V^1b-E^1b 

 

(I)

wherein;

W^1a is

2. The compound of claim 1 wherein at least one of E^1a and E^1b is —

N(H)C(═

O)OCH₃.

3. The compound of claim 1 wherein both of E^1a and E^1b are —

N(H)C(═

O)OCH₃.

4. The compound of claim 1 wherein at least one of V^1a and V^1b is selected from the group consisting of:

5. The compound of claim 1 wherein at least one of V^1a and V^1b is:

6. The compound of claim 1 wherein at least one of V^1a and V^1b is selected from the group consisting of:

7. The compound of claim 1 wherein V^1a and V^1b are each independently selected from the group consisting of:

8. The compound of claim 1 wherein at least one of P^1a and P^1b is selected from the group consisting of:

9. The compound of claim 1 wherein P^1a and P^1b are each independently selected from the group consisting of:

11. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof;

and at least one pharmaceutically acceptable carrier.

12. The pharmaceutical composition of claim 11, further comprising at least one therapeutic agent.

13. The pharmaceutical composition of claim 12, wherein said therapeutic agent is a ribavirin analog, NS3 protease inhibitor, NS5b polymerase inhibitor, alpha-glucosidase 1 inhibitor, hepatoprotectant, non-nucleoside inhibitor of HCV, or other drug for treating HCV.

14. The pharmaceutical composition of claim 11, further comprising a nucleoside analogue.

15. The pharmaceutical composition of claim 14, wherein said nucleoside analogue is selected from the group consisting of ribavirin, viramidine, levovirin, a L-nucleoside, and isatoribine.

16. A method of treating hepatitis C virus in a human patient in need thereof, said method comprising administering to the patient a pharmaceutical composition which comprises a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

10. A compound selected from the group consisting of: