1,4-benzodiazepine-2,5-diones with therapeutic properties
View Patent ↗The present invention relates to novel chemical compounds, methods for their discovery, and their therapeutic use. In particular, the present invention provides novel 1,4-benzodiazepine-2,5-dione compounds, and methods of using novel 1,4-benzodiazepine-2,5-dione compounds as therapeutic agents to treat a number of conditions associated with the faulty regulation of the processes of programmed cell death, autoimmunity, inflammation, hyperproliferation, and the like.
1. A compound represented by the following formula:
including both R and S enantiomeric forms, racemic mixtures, and pharmaceutically acceptable salts thereof; wherein:
R 1 is one of the following:
each of which is substituted or unsubstituted;
R 2 is selected from the group consisting of H and alkyl;
R 3 is selected from the group consisting of H, alkyl, and substituted alkyl;
R 4 is selected from the group consisting of halogen, —SO 2 R 4 ″, —SO 2 N(R 4 ′) 2 , —OR 4 ″, —N(R 4 ″) 2 , —CON(R 4 ″) 2 , —NHCOR 4 ″, —NHSO 2 R 4 ″, alkyl, mono-substituted alkyl, di-substituted alkyl, and tri-substituted alkyl; wherein R 4 ′ is independently selected from the group consisting of halogen, alkyl, mono-substituted alkyl, di-substituted alkyl, and tri-substituted alkyl; and R 4 ″ is independently selected from the group consisting of halogen, hydrogen, alkyl, mono-substituted alkyl, di-substituted alkyl, tri-substituted alkyl, aryl, mono-substituted aryl, di-substituted aryl, tri-substituted aryl, cycloaliphatic, mono-substituted cycloaliphatic, di-substituted cycloaliphatic, and tri-substituted cycloaliphatic; and
R 5 is selected from the group consisting of H and alkyl.
2. The compound of claim 1 , wherein R 1 is
which is substituted or unsubstituted.
3. The compound of claim 1 , wherein R 1 is
which is substituted or unsubstituted.
4. The compound of claim 1 , wherein R 1 is
which is substituted or unsubstituted.
5. The compound of claim 1 , wherein R 1 is
which is substituted or unsubstituted.
6. The compound of claim 1 , wherein R 3 is H or alkyl.
7. The compound of claim 1 , wherein R 4 is —SO 2 R 4 ″ or —SO 2 N(R 4 ′) 2 .
8. The compound of claim 1 , wherein R 4 is —OR 4 ″.
9. The compound of claim 1 , wherein R 4 is —N(R 4 ″) 2 or —CON(R 4 ″) 2 .
10. The compound of claim 1 , wherein R 4 is —NHCOR 4 ″ or —NHSO 2 R 4 ″.
11. The compound of claim 1 , wherein R 4 ′ is alkyl; and R 4 ″ is independently hydrogen, alkyl, or aryl.
12. The compound of claim 7 , wherein R 4 ′ is alkyl; and R 4 ″ is independently hydrogen, alkyl, or aryl.
13. The compound of claim 8 , wherein R 4 ″ is hydrogen, alkyl, or aryl.
14. The compound of claim 9 , wherein R 4 ″ is independently hydrogen, alkyl, or aryl.
15. The compound of claim 10 , wherein R 4 ″ is independently hydrogen, alkyl, or aryl.
16. The compound of claim 1 , wherein R 1 is
R 3 is H or alkyl; and R 4 is —SO 2 R 4 ″, —SO 2 N(R 4 ′) 2 , or —OR 4 ″.
17. The compound of claim 1 , wherein R 1 is
R 3 is H or alkyl; and R 4 is —N(R 4 ″) 2 , —CON(R 4 ″) 2 , —NHCOR 4 ″, or —NHSO 2 R 4 ″.
18. The compound of claim 1 , wherein the compound is one of the following:
or a pharmaceutically acceptable salt thereof.
19. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
20. A method of treating a disorder selected from the group consisting of graft-versus-host disease, rheumatoid arthritis, Sjogren's syndrome, myasthenia gravis, asthma, psoriasis, cancer, systemic lupus erythematosus, multiple sclerosis, Celiac Sprue, idiopathic thrombocytopenia purpura, scleroderma, Crohn's Disease, inflammatory bowel disease, and ulcerative colitis, comprising administering a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof to treat the disorder.