C17-alkanediyl and alkenediyl derivatives of oleanolic acid and methods of use thereof
Disclosed herein are novel C17-alkanediyl and alkenediyl derivatives of oleanolic acid, including those of the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising such compounds. Methods and intermediates useful for making the compounds, and methods of using the compounds, for example, as antioxidant inflammation modulators, and compositions thereof are also provided.
1. A compound of the formula:
wherein:
Y is —C(O)—; and
R 3 is:
hydrogen, hydroxy, halo, amino, —NHOH, or mercapto; or
alkyl (C≦8) , alkenyl (C≦8) , alkynyl (C≦8) , aryl (C≦8) , aralkyl (C≦8) , heteroaryl (C≦8) , heterocycloalkyl (C≦8) , acyl (C≦8) , alkoxy (C≦8) , alkenyloxy (C≦8) , aryloxy (C≦8) , aralkoxy (C≦8) , heteroaryloxy (C≦8) , acyloxy (C≦8) , heterocycloalkoxy (C≦8) , alkylamino (C≦8) , dialkylamino (C≦8) , alkenylamino (C≦8) , alkoxyamino (C≦8) , arylamino (C≦8) , aralkylamino (C≦8) , heteroarylamino (C≦8) , heterocycloalkylamino (C≦8) , alkylsulfonylamino (C≦8) , amido (C≦8) , —NH-amido (C≦8) , or a substituted version of any of these groups;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein the bond between carbon atoms a and b is a single bond.
3. The compound of claim 1 , wherein the bond between carbon atoms a and b is a double bond.
4. The compound of claim 1 , wherein R 3 is —H.
5. The compound of claim 1 , wherein R 3 is —OH.
6. The compound of claim 1 , wherein R 3 is amino.
7. The compound of claim 1 , wherein R 3 is alkyl (C≦8) .
8. The compound of claim 1 , wherein R 3 is heterocycloalkyl (C≦8) .
9. The compound of claim 1 , wherein R 3 is substituted heterocycloalkyl (C≦8) .
10. The compound of claim 1 , wherein R 3 is acyl (C≦8) .
11. The compound of claim 1 , wherein R 3 is substituted acyl (C≦8) .
12. The compound of claim 1 , wherein R 3 is alkoxy (C≦8) .
13. The compound of claim 1 , wherein R 3 is aryloxy (C≦8) .
14. The compound of claim 1 , wherein R 3 is aralkoxy (C≦8) .
15. The compound of claim 1 , wherein R 3 is substituted acyloxy (C≦8) .
16. The compound of claim 15 , wherein R 3 is —OC(O)NHCH 2 CH 3 .
17. The compound of claim 1 , wherein R 3 is heterocycloalkoxy (C≦8) .
18. The compound of claim 1 , wherein R 3 is alkylamino (C≦8) .
19. The compound of claim 1 , wherein R 3 is substituted alkylamino (C≦8) .
20. The compound of claim 19 , wherein R 3 is 2,2,2-trifluoroethylamino, —NHCH 2 C(O)OCH 3 or —NHCH 2 C(O)OH.
21. The compound of claim 1 , wherein R 3 is dialkylamino (C≦8) .
22. The compound of claim 1 , wherein R 3 is alkoxyamino (C≦8) .
23. The compound of claim 1 , wherein R 3 is arylamino (C≦8) .
24. The compound of claim 1 , wherein R 3 is aralkylamino (C≦8) .
25. The compound of claim 1 , wherein R 3 is heteroarylamino (C≦8) .
26. The compound of claim 1 , wherein R 3 is heterocycloalkylamino (C≦8) .
27. The compound of claim 1 , wherein R 3 is —NH-amido (C≦8) .
28. A pharmaceutical composition comprising:
a) the compound of claim 1 ; and
b) an excipient.
29. The compound of claim 1 , further defined as:
or a pharmaceutically acceptable salt thereof.
30. The compound of claim 1 , further defined as:
or a pharmaceutically acceptable salt thereof.