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, having a structure according to the formula:
wherein:
R 1a is H;
R 4a is a member selected from H, methyl, ethyl and substituted or unsubstituted aryl and substituted or unsubstituted arylalkyl;
R 10a is a member selected from H, halogen, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylthio, substituted or unsubstituted arylalkylthio;
R 11a is a member selected from H, OH, methyl, substituted or unsubstituted aryl, substituted or unsubstituted aryloxy, substituted or unsubstituted arylalkyloxy, substituted or unsubstituted arylthio, substituted or unsubstituted arylalkylthio;
or an anhydride, solvate or 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 the compound has a structure according to the formula:
4. The method of claim 3 , wherein R 10a is a member selected from
wherein
R 15 is a member selected from CN, COOH and
R 16 and R 17 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;
p is an integer selected from 1 to 5;
z is an integer selected from 1 to 8; and
X is a member selected from S and O.
5. The method of claim 1 , wherein the inflammatory-related disease is selected from the group consisting of arthritis, an inflammatory bowel disease, psoriasis, multiple sclerosis, a neurodegenerative disorder, congestive heart failure, stroke, aortic valve stenosis, kidney failure, lupus, pancreatitis, allergy, 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, HIV-related cachexia, cerebral malaria, ankylosing spondylitis, leprosy, anemia, and fibromyalgia.
6. The method of claim 5 , 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.
7. The method of claim 1 , wherein the inflammatory-related disease is dermatitis or eczema.
8. The method of claim 1 , wherein the inflammatory-related disease is contact dermatitis.
9. The method of claim 1 , wherein the inflammatory-related disease is atopic dermatitis.
10. The method of claim 1 , wherein the inflammatory-related disease is rheumatoid arthritis or psoriatic arthritis.
11. The method of claim 1 , wherein the inflammatory-related disease is psoriasis.
12. The method of claim 1 , wherein the inflammatory-related disease is rhinitis,
13. The method of claim 1 , wherein the inflammatory-related disease is allergic rhinitis.
14. The method of claim 1 , wherein the inflammatory-related disease is chronic obstructive pulmonary disease.
15. The method of claim 1 , wherein the inflammatory-related disease is asthma.
16. The method of claim 1 , wherein the inflammatory-related disease is bronchial asthma.
17. The method of claim 1 , wherein the inflammatory-related disease is allergic conjunctivitis.
18. The method of claim 1 , wherein the inflammatory-related disease is dry eye disease.
19. The method of claim 1 , wherein the inflammatory-related disease is uveitis.
20. The method of claim , wherein the inflammatory-related disease is Behcet's disease.
21. The method of claim 1 , wherein the inflammatory-related disease is sarcoidosis.
22. The method of claim 1 , wherein the inflammatory-related disease is Crohn's disease.
23. The method of claim 1 , wherein the inflammatory-related disease is ulcerative colitis.
24. The method of claim 1 , wherein the inflammatory-related disease is actinic keratosis.
25. The method of claim 1 , wherein the inflammatory-related disease is ankylosing spondylitis.
26. 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.