C17-alkanediyl and alkenediyl derivatives of oleanolic acid and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9593074-B2
Application number	US-201314022986-A
Country	US
Kind code	B2
Filing date	Sep 10, 2013
Priority date	Sep 10, 2012
Publication date	Mar 14, 2017
Grant date	Mar 14, 2017

Abstract

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.

First claim

What is claimed is:

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.

Assignees

• Reata Pharmaceuticals Inc

Inventors

• Bender Christopher F
• Jiang Xin
• Anderson Eric
• Visnick Melean

Classifications

• A61P39/06

  Free radical scavengers or antioxidants · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• C07J63/008 Primary

  Expansion of ring D by one atom, e.g. D homo steroids · CPC title

• C07D233/90

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07C255/47 Primary

  to carbon atoms of rings being part of condensed ring systems · CPC title