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Claims for Patent: 8,940,718

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Claims for Patent: 8,940,718

Title:Antiviral compounds
Abstract: The disclosure 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.
Inventor(s): Bacon; Elizabeth M. (Burlingame, CA), Cottell; Jeromy J. (Redwood City, CA), Katana; Ashley Anne (San Mateo, CA), Kato; Darryl (San Francisco, CA), Krygowski; Evan S. (Washington, DC), Link; John O. (San Francisco, CA), Taylor; James (San Mateo, CA), Tran; Chinh Viet (San Mateo, CA), Martin; Teresa Alejandra Trejo (Union City, CA), Yang; Zheng-Yu (Palo Alto, CA), Zipfel; Sheila (San Mateo, CA)
Assignee: Gilead Pharmasset LLC (Foster City, CA)
Application Number:13/679,874
Patent Claims: 1. A compound of formula (I): E.sup.1a-V.sup.1a--C(.dbd.O)--P.sup.1a--W.sup.1a--P.sup.1b--C(.dbd.O)--V.- sup.1b-E.sup.1b (I) wherein W.sup.1a is ##STR00179## and W.sup.1a is optionally substituted with one or more groups independently selected from halo, alkyl, haloalkyl, or cyano; Y.sup.5 is --O--CH.sub.2--, or --CH.sub.2--O--; X.sup.5 is --CH.dbd.CH--; E.sup.1a is --N(H)(alkoxycarbonyl), --N(H)(cycloalkylcarbonyl) or --N(H)(cycloalkyloxycarbonyl); or E.sup.1a-V.sup.1a taken together are R.sup.9a; E.sup.1b is --N(H)(alkoxycarbonyl), --N(H)(cycloalkylcarbonyl) or --N(H)(cycloalkyloxycarbonyl); or E.sup.1b-V.sup.1b taken together are R.sup.9b; V.sup.1a and V.sup.1b are each independently selected from: ##STR00180## P.sup.1a is selected from: ##STR00181## P.sup.1b is selected from: ##STR00182## and R.sup.9a and R.sup.9b are each independently: ##STR00183## or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 which has formula: ##STR00184## wherein the imidazole ring shown in formula A1 or A2 is optionally substituted with one or more groups independently selected from halo, haloalkyl, cyano, and alkyl; or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 which has formula: ##STR00185## wherein the imidazole ring shown in formula A2 is optionally substituted with one or more groups independently selected from halo, haloalkyl, cyano, or alkyl; or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 wherein at least one of E.sup.1a and E.sup.1b is --N(H)(alkoxycarbonyl).

5. The compound of claim 1 wherein both of E.sup.1a and E.sup.1b is --N(H)C(.dbd.O)OMe.

6. The compound of claim 1 wherein both of E.sup.1a and E.sup.1b are --N(H)C(.dbd.O)OMe.

7. The compound of claim 1 wherein at least one of E.sup.1a and E.sup.1b is --N(H)(cycloalkylcarbonyl) or --N(H)(cycloalkyloxycarbonyl).

8. The compound of claim 1 wherein at least one of E.sup.1a and E.sup.1b is cyclopropylcarbonylamino, cyclobutylcarbonylamino, cyclopropyloxycarbonylamino or cyclobutyloxycarbonylamino.

9. The compound of claim 1 wherein E.sup.1a and E.sup.1b are each independently selected from cyclopropylcarbonylamino, cyclobutylcarbonylamino, cyclopropyloxycarbonylamino or methoxycarbonylamino.

10. The compound of claim 1 wherein at least one of V.sup.1a and V.sup.1b is: ##STR00186##

11. The compound of claim 1 wherein E.sup.1a-V.sup.1a taken together are R.sup.9a or wherein E.sup.1b-V.sup.1b taken together are R.sup.9b.

12. The compound of claim 1 wherein at least one of P.sup.1a and P.sup.1b is selected from: ##STR00187##

13. The compound of claim 1 wherein P.sup.1a and P.sup.1b are each independently selected from: ##STR00188##

14. The compound of claim 1 wherein one of P.sup.1a and P.sup.1b is: ##STR00189## and the other of P.sup.1a and P.sup.1b is: ##STR00190##

15. The compound of claim 1 wherein one of P.sup.1a and P.sup.1b is: ##STR00191## and the other of P.sup.1a and P.sup.1b is: ##STR00192##

16. The compound of claim 1 wherein at least one of P.sup.1a and P.sup.1b is: ##STR00193##

17. The compound of claim 1 wherein at least one of P.sup.1a and P.sup.1b is: ##STR00194##

18. The compound of claim 1 wherein at least one of --V.sup.1a--C(.dbd.O)--P.sup.1a-- and --P.sup.1b--C(.dbd.O)--V.sup.1b-- is: ##STR00195##

19. The compound of claim 1 wherein at least one of --V.sup.1a--C(.dbd.O)--P.sup.1a-- and --P.sup.1b--C(.dbd.O)--V.sup.1b-- is: ##STR00196##

20. The compound of claim 1 wherein both of --V.sup.1a--C(.dbd.O)--P.sup.1a-- and --P.sup.1b--C(.dbd.O)--V.sup.1b-- are independently selected from: ##STR00197##

21. The compound of claim 1 wherein one of --V.sup.1a--C(.dbd.O)--P.sup.1a-- and --P.sup.1b--C(.dbd.O)--V.sup.1b-- is: ##STR00198## and the other of --V.sup.1a--C(.dbd.O)--P.sup.1a-- and --P.sup.1b--C(.dbd.O)--V.sup.1b-- is: ##STR00199##

22. The compound of claim 1 which is a compound of formula: ##STR00200## ##STR00201## ##STR00202## or a pharmaceutically acceptable salt thereof.

23. The compound of claim 1 which is a compound of formula: ##STR00203## ##STR00204## or a pharmaceutically acceptable salt thereof.

24. A pharmaceutical composition comprising the compound as described in claim 1 or a pharmaceutically acceptable salt thereof; and at least one pharmaceutically acceptable carrier.

25. The pharmaceutical composition according to claim 24, further comprising an inhibitor of HCV NS5B polymerase.

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

27. The method according to claim 26, further comprising administering an interferon or a pegylated interferon to the patient.

28. The method according to claim 26, further comprising administering ribavirin to the patient.
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