Details for Patent: 9,029,353

Title:	Boron-containing small molecules as anti-inflammatory agents
Abstract:	Methods of treating anti-inflammatory conditions through the use of boron-containing small molecules are disclosed.
Inventor(s):	Baker; Stephen J. (Mountain View, CA), Sanders; Virginia (San Francisco, CA), Akama; Tsutomu (Sunnyvale, CA), Bellinger-Kawahara; Carolyn (West Linn, OR), Freund; Yvonne (Los Altos, CA), Maples; Kirk R. (San Jose, CA), Plattner; Jacob J. (Orinda, CA), Zhang; Yong-Kang (San Jose, CA), Zhou; Huchen (Shanghai, CN), Hernandez; Vincent S. (Watsonville, CA)
Assignee:	Anacor Pharmaceuticals, Inc. (Palo Alto, CA)
Filing Date:	Jul 30, 2013
Application Number:	13/954,770
Claims:	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 selected from the group consisting of ##STR00128## 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 selected from the group consisting of: ##STR00129## 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 selected from the group consisting of ##STR00130## 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 selected from the group consisting of ##STR00131## 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 selected from the group consisting of ##STR00132## 11. The method according to claim 1, wherein the compound is administered at a concentration sufficient to inhibit a cytokine which is a member selected from IL-1.alpha., .beta., IL-2, IL-3, IL-6, IL-7, IL-9, IL-12,IL-17, IL-18, IL-23,TNF-.alpha., LT, LIF, Oncostatin, and IFNc1.alpha., .beta., .gamma.. 12. The method of claim 11, wherein the compound has a structure selected from the group consisting of ##STR00133## 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-.beta.. 14. The method of claim 13, wherein the compound has a structure selected from the group consisting of ##STR00134## 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 the compound of claim 1. 16. The method of claim 15, wherein the compound has a structure selected from the group consisting of ##STR00135## 17. 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. 18. The method of claim 17, wherein the compound has a structure selected from the group consisting of ##STR00136## 19. The method of claim 1, wherein the animal is a human being. 20. A method for inhibiting the production of an inflammatory cytokine protein by cells capable of producing said inflammatory cytokine protein, said method comprising: combining said cells with a therapeutic amount of the compound of claim 1, wherein production of said inflammatory cytokine by said cells is inhibited. 21. The method of claim 20, wherein the compound has a structure selected from the group consisting of ##STR00137## 22. The method of claim 20, wherein said therapeutic amount is sufficient to inhibit the production of said inflammatory cytokine protein between about 50% and about 99%. 23. 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 the compound of claim 1, wherein said inflammatory response is inhibited. 24. The method of claim 23, wherein the compound has a structure selected from the group consisting of ##STR00138## 25. The method of claim 1, wherein the compound has a structure which is ##STR00139## 26. The method of claim 1, wherein the compound has a structure which is ##STR00140## 27. The method of claim 7, wherein the compound has a structure which is ##STR00141## 28. The method of claim 7, wherein the compound has a structure which is ##STR00142## 29. The method of claim 1, wherein the disease is a member selected from psoriasis, arthritis, dermatitis, allergic rhinitis, ankylosing spondylitis, Crohn's disease, ulcerative colitis, chronic obstructive pulmonary disease, uveitis, sarcoidosis, Behcet's disease, allergic conjunctivitis, dry eye disease, asthma, and actinic keratosis. 30. The method of claim 29, wherein the compound has a structure which is ##STR00143## 31. The method of claim 29, wherein the compound has a structure which is ##STR00144## 32. The method of claim 1, wherein the disease is dermatitis. 33. The method of claim 32, wherein the compound has a structure which is ##STR00145## 34. The method of claim 32, wherein the compound has a structure which is ##STR00146## 35. The method of claim 1, wherein the disease is dermatitis, and said dermatitis is contact dermatitis or atopic dermatitis or eczema. 36. The method of claim 35, wherein the compound has a structure which is ##STR00147## 37. The method of claim 35, wherein the compound has a structure which is ##STR00148## 38. The method of claim 1, wherein the disease is arthritis, and said arthritis is rheumatoid arthritis. 39. The method of claim 38, wherein the compound has a structure which is ##STR00149## 40. The method of claim 38, wherein the compound has a structure which is ##STR00150## 41. The method of claim 1, wherein the disease is arthritis, and said arthritis is psoriatic arthritis. 42. The method of claim 41, wherein the compound has a structure which is ##STR00151## 43. The method of claim 41, wherein the compound has a structure which is ##STR00152## 44. The method of claim 1, wherein the disease is rhinitis, and said rhinitis is allergic rhinitis. 45. The method of claim 44, wherein the compound has a structure which is ##STR00153## 46. The method of claim 44, wherein the compound has a structure which is ##STR00154## 47. The method of claim 1, wherein the disease is rhinitis, and said rhinitis is bronchial asthma. 48. The method of claim 47, wherein the compound has a structure which is ##STR00155## 49. The method of claim 47, wherein the compound has a structure which is ##STR00156## 50. 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 ##STR00157## or a pharmaceutically acceptable salt thereof. 51. 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 ##STR00158## or a pharmaceutically acceptable salt thereof. 52. A method of treating psoriasis, comprising administering to the human or the animal a therapeutically effective amount of a compound having the following structure ##STR00159## or a pharmaceutically acceptable salt thereof. 53. A method of treating psoriasis, comprising administering to the human or the animal a therapeutically effective amount of a compound having the following structure ##STR00160## or a pharmaceutically acceptable salt thereof. 54. 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 ##STR00161## or a pharmaceutically acceptable salt thereof. 55. 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 ##STR00162## or a pharmaceutically acceptable salt thereof. 56. A method of treating eczema, comprising administering to the human or the animal a therapeutically effective amount of a compound having the following structure ##STR00163## or a pharmaceutically acceptable salt thereof. 57. A method of treating eczema, comprising administering to the human or the animal a therapeutically effective amount of a compound having the following structure ##STR00164## or a pharmaceutically acceptable salt thereof.