Proteasome inhibitors

1. A method of treating cancer, the method comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt or a boronic acid anhydride thereof, or a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt or a boronic acid anhydride thereof, and a pharmaceutically acceptable carrier:

with a second therapeutic agent, wherein:

Ring A is selected from the group consisting of

Z 1 and Z 2 are each hydroxyl, alkoxy, aryloxy, or aralkoxy, or Z 1 and Z 2 together form a moiety derived from a boronic acid complexing agent; and

wherein the cancer is multiple myeloma, lymphoma, or a recurrence of multiple myeloma or lymphoma.

2. The method of claim 1 , wherein Ring A is

and Z 1 and Z 2 are each hydroxyl, or Z 1 and Z 2 together form a moiety derived from a boronic acid complexing agent.

3. The method of claim 2 , wherein Z 1 and Z 2 are each hydroxyl.

4. The method of claim 1 , wherein the compound of formula (I) is selected from the group consisting of:

[(1R)-1-({[(2,3-difluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(5-chloro-2-fluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(3,5-difluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(2,5-difluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(2-bromobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(2-fluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(2-chloro-5-fluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(4-fluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(3,4-difluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(3-chlorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(2,5-dichlorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(3,4-dichlorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(3-fluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(2-chloro-4-fluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(2,3-dichlorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(2-chlorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(2,4-difluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(4-chloro-2-fluorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(4-chlorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid;

[(1R)-1-({[(2,4-dichlorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid; and

[(1R)-1-({[(3,5-dichlorobenzoyl)amino]acetyl}amino)-3-methylbutyl]boronic acid.

5. The method as in any one of claims 1 - 3 , wherein the cancer is multiple myeloma.

6. The method as in any one of claims 1 - 3 , wherein the cancer is lymphoma.

7. The method as in any one of claims 1 - 3 , wherein the patient in need of the treatment is a patient having or at risk of developing or experiencing a recurrence in a cancer selected from the group consisting of multiple myeloma and lymphoma.

8. The method as in any one of claims 1 - 3 , wherein the second therapeutic agent is melphalan.

9. The method as in any one of claims 1 - 3 , wherein the second therapeutic agent is lenalidomide.

10. The method as in any one of claims 1 - 3 , wherein the compound or pharmaceutical composition is administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vaginally or via an implanted reservoir.

11. The method of claim 10 , wherein the compound or composition is administered orally, intravenously, or subcutaneously.

12. The method of claim 10 , wherein the compound or composition is administered systemically.

13. The method of claim 10 , wherein the compound or composition is administered locally.

14. A method of treating cancer, the method comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of formula (I),

or a pharmaceutically acceptable salt or a boronic acid anhydride thereof, with lenalidomide wherein:

Ring A is

Z 1 and Z 2 are each hydroxyl, or Z 1 and Z 2 together form a moiety derived from a boronic acid complexing agent; and wherein the cancer is multiple myeloma, lymphoma, or a recurrence of multiple myeloma or lymphoma.

15. The method of claim 14 , wherein Z 1 and Z 2 are each hydroxyl.

16. The method of claim 15 , wherein Z 1 and Z 2 together form a moiety derived from a boronic acid complexing agent.

17. The method as in any one of claims 14 - 16 , wherein the cancer is multiple myeloma.

18. The method as in any one of claims 14 - 16 , wherein the cancer is lymphoma.

19. The method as in any one of claims 14 - 16 , wherein the patient in need of the treatment is a patient having or at risk of developing or experiencing a recurrence in a cancer selected from the group consisting of multiple myeloma and lymphoma.

20. A method of treating cancer, the method comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of formula (I),

or a pharmaceutically acceptable salt or a boronic acid anhydride thereof, with melphalan wherein:

Ring A is

and Z 1 and Z 2 are each hydroxyl, or Z 1 and Z 2 together form a moiety derived from a boronic acid complexing agent.

21. The method of claim 20 , wherein Z 1 and Z 2 are each hydroxyl.

22. The method of claim 20 , wherein Z 1 and Z 2 together form a moiety derived from a boronic acid complexing agent.

23. The method as in any one of claims 20 - 22 , wherein the cancer is multiple myeloma.

24. The method as in any one of claims 20 - 22 , wherein the cancer is lymphoma.

25. The method as in any one of claims 20 - 22 , wherein the patient in need of the treatment is a patient having or at risk of developing or experiencing a recurrence in a cancer selected from the group consisting of multiple myeloma and lymphoma.