Boron-containing small molecules as anti-inflammatory agents
Methods of treating anti-inflammatory conditions through the use of boron-containing small molecules are disclosed.
1. A method of treating an inflammatory-related disease in a human or an animal, said method comprising administering to the human or the animal a therapeutically effective amount of a compound which is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , further comprising administering said compound as part of a pharmaceutical formulation, said formulation further comprising a pharmaceutically acceptable excipient.
3. The method of claim 1 , wherein said compound is present in a form which is a member selected from a hydrate with water, a solvate with an alcohol, an adduct with an amino compound, and an adduct with an acid.
4. The method of claim 1 , wherein said compound has a structure which is selected from the group consisting of
5. The method of claim 1 , wherein the compound is in an amount sufficient to treat the inflammatory-related disease by inhibiting pro-inflammatory cytokine expression or by stimulating anti-inflammatory cytokine expression, but the amount is less than sufficient to substantially inhibit cyclin dependent kinases.
6. The method of claim 5 , wherein the compound has a structure which is selected from the group consisting of
7. The method of claim 1 , wherein the disease is a member selected from arthritis, rheumatoid arthritis, an inflammatory bowel disease, psoriasis, multiple sclerosis, a neurodegenerative disorder, congestive heart failure, stroke, aortic valve stenosis, kidney failure, lupus, pancreatitis, allergy, fibrosis, anemia, atherosclerosis, a metabolic disease, a bone disease, a cardiovascular disease, a chemotherapy/radiation related complication, diabetes type I, diabetes type II, a liver disease, a gastrointestinal disorder, an ophthalmological disease, allergic conjunctivitis, diabetic retinopathy, Sjogren's syndrome, uveitis, a pulmonary disorder, a renal disease, dermatitis, HIV-related cachexia, cerebral malaria, ankylosing spondylitis, leprosy, anemia and fibromyalgia.
8. The method of claim 7 , wherein the compound has a structure which is selected from the group consisting of
9. The method of claim 7 , wherein the neurodegenerative disorder is a member selected from Alzheimer's disease and Parkinson disease, the inflammatory bowel disease is a member selected from Crohn's disease or ulcerative colitis; the gastrointestinal complication is diarrhea; the liver disease is a member selected from an autoimmune hepatitis, hepatitis C, primary biliary cirrhosis, primary sclerosing cholangitis and fulminant liver failure; the gastrointestinal disorder is a member selected from celiac disease and non-specific colitis; the pulmonary disorder is a member selected from allergic rhinitis, asthma, chronic obstructive pulmonary disease, chronic granulomatous inflammation, cystic fibrosis, and sarcoidosis; the cardiovascular disease is a member selected from atheroscleotic cardiac disease, congestive heart failure and restenosis; and the renal disease is a member selected from glomerulonephritis and vasculitis.
10. The method of claim 9 , wherein the compound has a structure which is selected from the group consisting of
11. The method of claim 1 , wherein the compound is administered at a concentration sufficient to inhibit a cytokine which is a member selected from IL-1α, β, IL-2, IL-3, IL-6, IL-7, IL-9, IL-12, IL-17, IL-18, IL-23, TNF-α, LT, LIF, Oncostatin, and IFNc1α, β, γ.
12. The method of claim 11 , wherein the compound has a structure which is selected from the group consisting of
13. The method of claim 1 , where the compound is administered at a concentration sufficient to stimulate expression of a cytokine which is a member selected from IL-4, IL-10, IL-11, W-13 and TGF-β.
14. The method of claim 13 , wherein the compound has a structure which is selected from the group consisting of
15. A method of treating an inflammatory-related disease associated with cytokine expression levels, which comprises administering to a human or an animal in need of such treatment a compound which is selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
16. The method of claim 15 , wherein the compound has a structure which is selected from the group consisting of
17. The method of claim 1 , wherein the animal is a human being.
18. A method for inhibiting the production of an inflammatory cytokinc protein by cells capable of producing said inflammatory cytokine protein, said method comprising: combining said cells with a therapeutic amount of, a compound which is selected from the group consisting of
or a pharmaceutically acceptable salt thereof, wherein production of said inflammatory cytokine by said cells is inhibited.
19. The method of claim 18 , wherein the compound has a structure which is selected from the group consisting of
20. The method of claim 18 , wherein said therapeutic amount is sufficient to inhibit the production of said inflammatory cytokine protein between about 50% and about 99%.
21. A method for inhibiting an inflammatory response in a human or an animal, said method comprising: contacting said human or animal with a therapeutic amount of a compound which is selected from the group consisting of
or a pharmaceutically acceptable salt thereof, wherein said inflammatory response is inhibited.
22. The method of claim 21 , wherein the compound has a structure which is selected from the group consisting of
23. The method of claim 1 , wherein the disease is a member selected from Crohn's disease, ulcerative colitis, arthritis, rheumatoid arthritis, psoriasis, Alzheimer's disease, Parkinson disease, atopic dermatitis, and actinic keratosis.
24. The method of claim 23 , wherein the compound has a structure selected from the group consisting of
25. A method of treating an inflammatory-related disease in a human or an animal, said method comprising administering to the human or the animal a therapeutically effective amount of a compound having the following structure
or a pharmaceutically acceptable salt thereof.
26. A method of treating an inflammatory-related disease in a human or an animal, said method comprising administering to the human or the animal a therapeutically effective amount of a compound having the following structure
or a pharmaceutically acceptable salt thereof.
27. A method of treating psoriasis, comprising administering to the human or the animal a therapeutically effective amount of a compound having the following structure
or a pharmaceutically acceptable salt thereof.
28. A method of treating psoriasis, comprising administering to the human or the animal a therapeutically effective amount of a compound having the following structure
or a pharmaceutically acceptable salt thereof.
29. A method of treating atopic dermatitis, comprising administering to the human or the animal a therapeutically effective amount of a compound having the following structure
or a pharmaceutically acceptable salt thereof.
30. A method of treating atopic dermatitis, comprising administering to the human or the animal a therapeutically effective amount of a compound having the following structure
or a pharmaceutically acceptable salt thereof.
31. The method of claim 25 , wherein the inflammatory-related disease is dermatitis or eczema.
32. The method of claim 25 , wherein the inflammatory-related disease is contact dermatitis.
33. The method of claim 25 , wherein the inflammatory-related disease is rheumatoid arthritis or psoriatic arthritis.
34. The method of claim 26 , wherein the inflammatory-related disease is dermatitis or eczema.
35. The method of claim 26 , wherein the inflammatory-related disease is contact dermatitis.
36. The method of claim 26 , wherein the inflammatory-related disease is rheumatoid arthritis or psoriatic arthritis.