Fumarate analogs and uses thereof
Aspects of the present disclosure include compounds that find use for the treatment of a variety of autoimmune and inflammatory diseases and disorders. 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.
1. A method of treating a disease of disorder in a subject in need thereof, the method comprising:
administering to the subject a pharmaceutically effective amount of a compound of formula (IIa) or (IIb):
wherein:
R 1 is selected from hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, heterocyclyl, substituted heterocyclyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl; and
X 1 is hydrogen or C 1-6 alkyl;
or a salt or stereoisomer thereof,
wherein the administering is sufficient to treat the disease or disorder, and 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 R 1 is aryl, substituted aryl, heteroaryl, or substituted heteroaryl.
3. The method of claim 1 , wherein R 1 is hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl.
4. The method of claim 3 , wherein R 1 is hydrogen, methyl, ethyl, isopropyl, cyclopentyl, 4-tetrahydropyranyl, —CH 2 CH 2 OCH 3 , —CH 2 OCH 3 , —CH 2 C(O)OCH 3 , or —CH 2 CH(CH 3 ) 2 OH.
5. The method of claim 1 , wherein X 1 is C 1-6 alkyl.
6. The method of claim 5 , wherein X 1 is methyl or tert-butyl.
7. The method of claim 1 , wherein R 1 is:
wherein X 1b is selected from C 1-6 alkyl and a progroup.
8. The method of claim 7 , wherein the compound has one of the following formulae:
wherein X 1 and X 1b are each independently selected from C 1-6 alkyl and a progroup.
9. The method of claim 8 , wherein X 1 and X 1b are each independently a C 1-6 alkyl.
10. The method of claim 9 , wherein the compound has the structure:
11. The method of claim 1 , wherein the compound is selected from:
12. The method of claim 1 , wherein the compound is selected from:
13. The method of claim 1 , wherein the disease or disorder is cardiac insufficiency.
14. The method of claim 13 , wherein the cardiac insufficiency is selected from the group consisting of left ventricular insufficiency, myocardial infarction, and angina pectoris.
15. The method of claim 1 , wherein the disease or disorder is asthma.
16. The method of claim 1 , wherein the disease or disorder is arthritis.
17. The method of claim 16 , 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.
18. The method of claim 1 , wherein the disease or disorder is an inflammatory bowel disease.
19. The method of claim 18 , wherein the inflammatory bowel disease is selected from the group consisting of Crohn's disease and ulcerative colitis.
20. The method of claim 19 , wherein the inflammatory bowel disease is Crohn's disease.
21. The method of claim 1 , wherein the disease or disorder is a chronic obstructive pulmonary disease.
22. The method of claim 21 , wherein the chronic obstructive pulmonary disease is selected from the group consisting of bronchitis and emphysema.