p38α mitogen-activated protein kinase inhibitors

1. A compound having the structure of Formula (1):

or a pharmaceutically acceptable salt thereof, wherein,

R 1 is selected from C 1-4 alkanediyl and C 1-4 heteroalkanediyl; and

R 2 is a moiety having the structure of Formula (2d):

wherein,

each of A 1 and A 2 is independently selected from —CH2— and —C(═O)—;

each n is independently selected from 1, 2, and 3; and

X is —NR 3 — and R 3 is —C(═O)—CH3.

2. The compound of claim 1 , wherein R 1 is C 1-4 alkanediyl.

3. The compound of claim 1 , wherein R 1 is selected from methanediyl and ethanediyl.

4. The compound of claim 1 , wherein one n is 1 and the other n is selected from 2 and 3.

5. The compound of claim 1 , wherein each n is 2 or each n is 3.

6. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof.

7. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition comprises a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof for treating a disease in a patient, wherein the etiology of the disease is associated with up-regulation of the p38α MAPK protein, with the down-regulation of the p38α MAPK protein, or with both the up-regulation and the down-regulation of the p38α MAPK protein.

8. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition comprises a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof for treating a disease in a patient, wherein the disease is selected from cancer, an inflammatory disease, and autoimmune disease, and a viral disease.

9. The pharmaceutical composition of claim 6 , wherein the pharmaceutical composition comprises a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof for treating a disease in a patient, wherein the disease is selected from acute lung injury, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), amyotrophic lateral sclerosis, and cystic fibrosis.

10. A method of treating a disease in a patient comprising administering to a patient in need thereof a therapeutically effective of amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the disease is selected from cancer, an inflammatory disease, an autoimmune disease, and a viral disease.

11. A method of treating a disease in a patient comprising administering to a patient in need thereof a therapeutically effective of amount of the pharmaceutical composition of claim 6 , wherein the disease is selected from cancer, an inflammatory disease, an autoimmune disease, and a viral disease.

12. A compound having the structure of Formula (1):

or a pharmaceutically acceptable salt thereof, wherein,

R 1 is C 1-4 alkanediyl; and

R 2 is a moiety having the structure of Formula(2d

wherein,

each n is independently selected from, 1, 2, and 3;

each of A 1 and A 2 is independently selected from —CH 2 and —C(═O)—,

and at least one of A 1 and A 2 is —C(═O)—; and

X is —NR 3 —, wherein R 3 is selected from hydrogen, C 1-6 alkyl, and substituted C 1-6 alkyl.

13. The compound of claim 12 , wherein each substituent is selected from —OH and ═o.

14. The compound of claim 12 , wherein R 1 is selected from methanediyl and ethanediyl.

15. A compound having the structure of Formula (1):

or a pharmaceutically acceptable salt thereof, wherein,

R 1 is selected from C 1-4 alkanediyl, C 1-4 heteroalkanediyl, substituted C 1-4 alkanediyl, and substituted C 1-4 heteroalkanediyl; and

R 2 is a moiety having the structure of Formula (2d):

wherein,

one n is 1 and the other n is selected from 2 and 3;

each of A 1 and A 2 is independently selected from —CH 2 — and —C(═O)—, and at least one of A 1 and A 2 is —C(═O)—; and

X is —NR 3 —, wherein R 3 is selected from hydrogen, C 1-6 alkyl, and substituted C 1-6 alkyl.

16. The compound of claim 12 , wherein each n is 2 or each n is 3.

17. The compound of claim 12 , wherein the compound is selected from:

4-chloro-N-(4-((3-oxopiperazin-1-yl)methyl)phenyl)benzamide (15); and

4-chloro-N-(4-((4-methyl-3-oxopiperazin-1-yl)methyl)phenyl)benzamide (16);

or a pharmaceutically acceptable salt of any of the foregoing.

18. A pharmaceutical composition comprising the compound of claim 12 or a pharmaceutically acceptable salt thereof.

19. The pharmaceutical composition of claim 18 , wherein the pharmaceutical composition comprises a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof for treating a disease in a patient, wherein the etiology of the disease is associated with up-regulation of the p38α MAPK protein, with the down-regulation of the p38α MAPK protein, or with both the up-regulation and the down-regulation of the p38α MAPK protein.

20. The pharmaceutical composition of claim 18 , wherein the pharmaceutical composition comprises a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof for treating a disease in a patient, wherein the disease is selected from cancer, an inflammatory disease, and autoimmune disease, and a viral disease.

21. The pharmaceutical composition of claim 18 , wherein the pharmaceutical composition comprises a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof for treating a disease in a patient, wherein the disease is selected from acute lung injury, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), amyotrophic lateral sclerosis, and cystic fibrosis.

22. A method of treating a disease in a patient comprising administering to a patient in need thereof a therapeutically effective of amount of the compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein the disease is selected from cancer, an inflammatory disease, an autoimmune disease, and a viral disease.

23. A method of treating a disease in a patient comprising administering to a patient in need thereof a therapeutically effective of amount of the pharmaceutical composition of claim 18 , wherein the disease is selected from cancer, an inflammatory disease, an autoimmune disease, and a viral disease.

24. A pharmaceutical composition comprising the compound of claim 15 or a pharmaceutically acceptable salt thereof.

25. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition comprises a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof for treating a disease in a patient, wherein the etiology of the disease is associated with up-regulation of the p38α MAPK protein, with the down-regulation of the p38α MAPK protein, or with both the up-regulation and the down-regulation of the p38α MAPK protein.

26. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition comprises a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof for treating a disease in a patient, wherein the disease is selected from cancer, an inflammatory disease, and autoimmune disease, and a viral disease.

27. The pharmaceutical composition of claim 24 , wherein the pharmaceutical composition comprises a therapeutically effective amount of the compound or a pharmaceutically acceptable salt thereof for treating a disease in a patient, wherein the disease is selected from acute lung injury, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), amyotrophic lateral sclerosis, and cystic fibrosis.

28. A method of treating a disease in a patient comprising administering to a patient in need thereof a therapeutically effective of amount of the compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein the disease is selected from cancer, an inflammatory disease, an autoimmune disease, and a viral disease.

29. A method of treating a disease in a patient comprising administering to a patient in need thereof a therapeutically effective of amount of the pharmaceutical composition of claim 15 , wherein the disease is selected from cancer, an inflammatory disease, an autoimmune disease, and a viral disease.