Pyrazolyl and pyrimidinyl tricyclic enones as antioxidant inflammation modulators

1. A compound of the formula:

wherein:

n is 1 or 2;

R 1 and R 2 are each independently hydrogen, alkyl (C≤12) , aryl (C≤12) , or aralkyl (C≤12) ;

or

R 1 and R 2 are taken together and are alkanediyl (C≤12) ;

R 3 is absent, hydrogen, alkyl (C≤12) , or aryl (C≤12) ;

R 5 is absent, hydrogen, alkyl (C≤12) , substituted alkyl (C≤12) , or aryl (C≤12) ; and

R 6 is hydrogen, amino, halo, cyano, or oxo; or

alkyl (C≤12) , —C≡C-trimethylsilyl, aryl (C≤12) , aralkyl (C≤12) , heteroaryl (C≤12) , acyl (C≤12) , alkoxy (C≤12) , amido (C≤2) , or a substituted version of any of these groups; or

or a salt or tautomer thereof.

2. The compound of claim 1 , wherein n is 1.

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

4. The compound according to any one of claims 1 - 3 , wherein R 1 or R 2 is hydrogen.

5. The compound of claim 4 , wherein R 1 and R 2 are each hydrogen.

6. The compound of claim 4 , wherein R 1 is alkyl (C≤12) and R 2 is hydrogen.

7. The compound of claim 6 , wherein R 1 is methyl or ethyl.

8. The compound of claim 4 , wherein R 1 is aryl (C≤12) or aralkyl (C≤12) and R 2 is hydrogen.

9. The compound of claim 8 , wherein R 1 is phenyl or benzyl.

10. The compound according to any one of claims 1 - 3 , wherein R 1 and R 2 are alkyl (C≤12) .

11. The compound of claim 10 , wherein R 1 and R 2 are each methyl.

12. The compound according to any one of claims 1 - 3 , wherein R 1 and R 2 are aralkyl (C≤12) .

13. The compound of claim 12 , wherein R 1 and R 2 are each benzyl.

14. The compound according to any one of claims 1 - 3 , wherein R 1 and R 2 are taken together and are alkanediyl (C≤12) .

15. The compound according to any one of claims 1 - 3 , wherein R 3 is absent.

16. The compound according to any one of claims 1 - 3 wherein R 5 is alkyl (C≤12) or substituted alkyl (C≤12) .

17. The compound of claim 16 wherein R 5 is methyl, tert-butyl, cyclohexyl, trifluoromethyl or 1-hydroxyeth-2-yl.

18. The compound according to any one of claims 1 - 3 , wherein R 5 is aryl (C≤12) .

19. The compound of claim 18 , wherein R 5 is phenyl.

20. The compound according to any one of claims 1 - 3 , wherein R 6 is hydrogen, amino, halo, cyano, or oxo.

21. The compound of claim 20 wherein R 6 is hydrogen.

22. The compound of claim 20 , wherein R 6 is amino.

23. The compound of claim 20 , wherein R 6 is halo.

24. The compound of claim 23 , wherein R 6 is bromo or chloro.

25. The compound of claim 20 , wherein R 6 is cyano.

26. The compound according to any one of claims 1 - 3 , wherein R 6 is alkyl (C≤12) .

27. The compound according to any one of claims 1 - 3 , wherein R 6 is aryl (C≤12) or substituted aryl (C≤12) .

28. The compound of claim 27 , wherein R 6 is phenyl, 2-methylphenyl, 3-methylphenyl, or 4-methylphenyl or 3-chlorophenyl, 4-chlorophenyl, 2-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-methoxyphenyl, 3-methoxyphenyl, or 4-methoxyphenyl.

29. The compound according to any one of claims 1 - 3 , wherein R 6 is heteroaryl (C≤12) .

30. The compound of claim 29 , wherein R 6 is 3-pyridyl, 4-pyridyl, 2-methyl-2H-tetrazol-5-yl, 2-benzyl-2H-tetrazol-5-yl, 5-methyl-1,2,4-oxadiazol-3-yl, 5-methyl-1,3,4-oxadiazol-2-yl, 3-methyl-1,2,4-oxadiazol-5-yl, 1-methyl-1H-1,2,4-triazol-3-yl, 1-methyl-1H-pyrazol-4-yl, 2-pyridyl, or 1-isopropyl-1H-1,2,4-triazol-3-yl.

31. The compound according to any one of claims 1 - 3 , wherein R 6 is amido (C≤12) .

32. The compound according to any one of claims 1 - 3 , wherein R 6 is acyl (C≤12) or substituted acyl (C≤12) .

33. The compound according to any one of claims 1 - 3 , wherein R 6 is alkoxy (C≤12) .

34. The compound of claim 33 wherein R 6 is methoxy.

35. The compound of claim 32 , wherein R 6 is substituted acyl (C≤12) .

36. The compound of claim 35 , wherein R 6 is —C(O)-methoxy or —C(O)-ethoxy.

37. The compound of claim 1 , wherein the compound is further defined as:

or a salt or a tautomer thereof.