Nrf2 activating compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-11279686-B2
Application number	US-202017075152-A
Country	US
Kind code	B2
Filing date	Oct 20, 2020
Priority date	Feb 3, 2016
Publication date	Mar 22, 2022
Grant date	Mar 22, 2022

Abstract

Aspects of the present disclosure include compounds that activate Nrf2. Such compounds find use in the treatment of autoimmune and inflammatory diseases and disorders, such as for example psoriasis and multiple sclerosis. Embodiments of the present disclosure also relate to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

First claim

What is claimed is:

1. A method of treating a disease or disorder in a subject having said disease or disorder, the method comprising administering to the subject a pharmaceutically effective amount of a compound of formula (I):

wherein:
X 1 and X 2 are each independently selected from N and CH, wherein at least one of X 1 and X 2 is N;
either Y 1 is sulfonyl and Y 2 is hydrogen, or Y 2 is sulfonyl and Y 1 is hydrogen; and
each R 1 is independently selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl and R 15 , wherein R 15 comprises a linking group and a compound of formula (I);
or a salt or stereoisomer thereof,
wherein the disease or disorder is selected from the group consisting of cardiac insufficiency, asthma, arthritis, an inflammatory bowel disease, and a chronic obstructive pulmonary disease.

2. The method of claim 1 , wherein the disease or disorder is cardiac insufficiency.

3. The method of claim 2 , wherein the cardiac insufficiency is selected from the group consisting of left ventricular insufficiency, myocardial infarction, and angina pectoris.

4. The method of claim 1 , wherein the disease or disorder is asthma.

5. The method of claim 1 , wherein the disease or disorder is arthritis.

6. The method of claim 5 , wherein the arthritis is selected from the group consisting of inflammatory arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis (juvenile idiopathic arthritis), psoriatic arthritis, and ankylosing spondylitis.

7. The method of claim 1 , wherein the disease or disorder is an inflammatory bowel disease.

8. The method of claim 7 , wherein the inflammatory bowel disease is selected from the group consisting of Crohn's disease and ulcerative colitis.

9. The method of claim 7 , wherein the inflammatory bowel disease is Crohn's disease.

10. The method of claim 1 , wherein the disease or disorder is a chronic obstructive pulmonary disease.

11. The method of claim 10 , wherein the chronic obstructive pulmonary disease is selected from the group consisting of bronchitis and emphysema.

12. The method of claim 1 , wherein the compound is a compound of formula (II):

or
wherein the compound is a compound of formula (III):

or
wherein the compound is a compound of formula (IV):

13. The method of claim 1 , wherein the sulfonyl is selected from alkyl-SO 2 —, substituted alkyl-SO 2 —, alkenyl-SO 2 —, substituted alkenyl-SO 2 —, cycloalkyl-SO 2 —, substituted cycloalkyl-SO 2 —, heterocycloalkyl-SO 2 —, substituted heterocycloalkyl-SO 2 —, aryl-SO 2 —, substituted aryl-SO 2 —, heteroaryl-SO 2 —, and substituted heteroaryl-SO 2 —.

14. The method of claim 1 , wherein R 1 is alkyl, substituted alkyl, heteroaryl, or substituted heteroaryl.

15. The method of claim 1 , wherein the compound is selected from:

Assignees

• Rigel Pharmaceuticals Inc

Inventors

• Duncton Matthew
• Singh Rajinder

Classifications

• A61P29/00

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

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P17/06

  Antipsoriatics · CPC title

• A61K31/22

  of acyclic acids, e.g. pravastatin · CPC title

• A61K31/216 Primary

  of acids having aromatic rings, e.g. benactizyne, clofibrate · CPC title