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

Patent metadata

Field	Value
Publication number	US-10501489-B2
Application number	US-201715433100-A
Country	US
Kind code	B2
Filing date	Feb 15, 2017
Priority date	Sep 10, 2012
Publication date	Dec 10, 2019
Grant date	Dec 10, 2019

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:
n is 1 to 6;
R 1 and R 2 are each independently —H, —OH, methyl, or as defined below; and
R 3 is:
amino or —NHOH; or
N-heteroaryl (C≤8) , N-heterocycloalkyl (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;
R 3 and R 1 , taken together, are —NR a —, wherein R a is hydrogen or alkyl (C≤4) ; or
R 3 and R 2 , taken together, are wherein —NR a — is hydrogen or alkyl (C≤4) ; or

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , further defined as:

wherein:
n is 1 to 6; and
R 3 is:
amino or —NHOH; or
N-heteroaryl (C≤8) , N-heterocycloalkyl (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) , alkyl sulfonylamino (C≤8) , amido (C≤8) , —NH-amido (C≤8) , or a substituted version of any of these groups;

or a pharmaceutically acceptable salt thereof.

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

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

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

6. The compound of claim 1 , wherein R 1 is —H.

7. The compound of claim 1 , wherein R 2 is methyl.

8. The compound of claim 1 , wherein R 3 is N-heteroaryl (C≤8) .

9. The compound of claim 8 , wherein R 3 is imidazolyl.

10. The compound of claim 1 , wherein R 3 is N-heterocycloalkyl (C≤8) .

11. The compound of claim 10 , wherein R 3 is morpholinyl or pyrrolidinyl.

12. The compound of claim 1 , wherein R 3 is alkylamino (C≤8) .

13. The compound of claim 12 , wherein R 3 is ethylamino.

14. The compound of claim 1 , further defined as:

or a pharmaceutically acceptable salt thereof.

15. A pharmaceutical composition comprising:
a) the compound of claim 1 ; and
b) an excipient.

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

• C07D211/46

  having a hydrogen atom as the second substituent in position 4 · CPC title

• C07D213/75

  Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates · CPC title

• C07D207/08

  with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms · CPC title