C4-modified oleanolic acid derivatives for inhibition of IL-17 and other uses

Patent metadata

Field	Value
Publication number	US-11584775-B2
Application number	US-201615760662-A
Country	US
Kind code	B2
Filing date	Sep 23, 2016
Priority date	Sep 23, 2015
Publication date	Feb 21, 2023
Grant date	Feb 21, 2023

Abstract

Disclosed herein are C4 modified oleanolic acid derivatives of the formula: Formula (X) or Formula (XII), as well as analogs thereof, wherein the variables are defined herein. In addition, disclosed herein are pharmaceutical compositions of these derivatives or analogs, methods for their manufacture, and methods for their use, including for the prevention and treatment of diseases or disorders associated with overproduction of IL-17.

First claim

What is claimed is:

1. A compound of the formula:

wherein:
R 1 is alkyl (C≤8) ;
R 3 is hydrogen or hydroxy, or R 3 is taken together with Y as described below;
Y is heteroaryl (C≤8) or substituted versions thereof;
—C(O)R c , wherein R c is hydroxy, alkoxy (C≤8) ; alkylamino (C≤8) , dialkyl-amino (C≤8) , or a substituted version of any of these groups;
—NR d C(O)R e , wherein: R d is hydrogen; and R e is alkyl (C≤8) , alkoxy (C≤8) , or a substituted version of any of these groups; or

Y is taken together with R 3 and is —C(O)O—;

wherein when the terms alkyl, alkoxy, alkylamino, dialkylamino, and heteroaryl are used with the substituted modifier, one or more hydrogen atom has been independently replaced by —F;
or a pharmaceutically acceptable salt thereof.

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

3. The compound of claim 1 , wherein Y is heteroaryl (C≤8) or substituted heteroaryl (C≤8) .

4. The compound of claim 1 , wherein Y is taken together with R 3 and is —C(O)O—.

5. The compound of claim 1 , wherein Y is —C(O)R c , wherein R c is hydroxy or alkoxy (C ≤8) .

6. The compound of claim 1 , wherein R3 is hydrogen.

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

or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising:
(A) a compound of claim 1 ; and
(B) an excipient or a pharmaceutically acceptable carrier.

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

or a pharmaceutically acceptable salt thereof.

10. A pharmaceutical composition comprising:
(A) a compound of claim 9 ; and
(B) an excipient or a pharmaceutically acceptable carrier.

Assignees

• Reata Pharmaceuticals Inc

Inventors

• Visnick Melean
• Jiang Xin
• Hotema Martha R
• Lee Chitase
• Caprathe Bradley William
• Roark William H
• Bolton Gary L

Classifications

• C07J71/0005

  Oxygen-containing hetero ring · CPC title

• C07J63/008 Primary

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

• A61P29/00

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

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title