BORON-CONTAINING SMALL MOLECULES

• US 20110166103A1
• Filed: 09/01/2009
• Published: 07/07/2011
• Est. Priority Date: 09/04/2008
• Status: Active Grant

• Current Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Original Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Inventors: Akama, Tsutomu, Plattner, Jacob J.
• Granted Patent: US 8,470,803 B2
• Time in Patent Office: Days
• US Class Current: 514/64
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/08 : for leprosy
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 39/00 : General protective or antinoxious agents
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
• CPC Class Codes: C07F 5/025 : Boronic and borinic acid compounds

Abstract

This invention provides, among other things, novel compounds useful for treating inflammatory conditions, pharmaceutical compositions containing such compounds, as well as combinations of these compounds with at least one additional therapeutically effective agent.

Claims

1. A compound having a structure according to the formula:

2. The compound of claim 1, having a structure which is

3. The compound of claim 1, having a structure which is

4. The compound of claim 1, having a structure which is

5. The compound of claim 1, having a structure which is

6. The compound of claim 1, having a structure which is

7. The compound of claim 1, having a structure which is

10. The compound of claim 1, having a structure which is selected from the group consisting of

11. The compound of any of claims 1-8, wherein R^b is OR⁴, and R⁴ is cycloalkylsubstituted alkyl.

12. The compound of claim 1, having a structure which is selected from the group consisting of

13. The compound of any of claims 1-8, wherein R^b is OR⁴, and R⁴ is substituted or unsubstituted heteroalkyl.

14. The compound of claim 1, having a structure which is selected from the group consisting of

15. The compound of any of claims 1-8, wherein R^b is NR⁴R⁵, and R⁴ and R⁵ are each independently selected from the group consisting of 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.

16. The compound of any of claims 1-8, wherein R^b is NHR⁵, and R⁵ is selected from the group consisting of 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.

17. The compound of any of claims 1-8, wherein R^b is NHR⁵, and R⁵ is substituted or unsubstituted heteroalkyl.

18. The compound of claim 1, having a structure which is selected from the group consisting of

19. A pharmaceutical formulation comprising:

(a) the compound of any preceding claim;

(b) a pharmaceutically acceptable excipient.

20. The formulation of claim 19, wherein the formulation is in a unit dosage form.

21. The formulation of claim 19, wherein the formulation is for oral or topical use.

22. A method of decreasing the release of a cytokine or a chemokine, the method comprising:

contacting a cell with the compound of claim 1, wherein the release of the cytokine or chemokine by the cell is decreased.

23. The method according to claim 22, wherein the cytokine is selected from the group consisting of IL-1α

, IL-1β

, IL-2, IL-3, IL-6, IL-7, IL-9, IL-12, IL-17, IL-18, IL-23, TNF-α

, LT, LIF, Oncostatin, IFNα

, IFNβ and

IFN-γ

.

24. The method according to claim 22, wherein the cytokine is selected from the group consisting of IL-1β

, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-23, TNF-α and

IFN-γ

.

25. The method according to claim 22, wherein the cytokine is selected from the group consisting of IL-2, IL-5, IL-10, IL-12, IL-23, TNF-α

and IFN-γ

.

26. The method according to claim 22, wherein the chemokine is selected from the group consisting of IL-8, Gro-α

, MIP-1, MCP-1, PGE2, ENA-78, and RANTES.

27. A method of treating a condition, in an animal, the method comprising administering to the animal a therapeutically effective amount of the compound of claim 1, thereby treating the condition.

28. The method of claim 27, wherein the condition is selected from the group consisting of arthritis, rheumatoid arthritis, an inflammatory bowel disease, psoriasis, a pulmonary disease, 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 ophthamological disease, allergic conjunctivitis, diabetic retinopathy, Sjogren'"'"'s syndrome, uveitis, a pulmonary disorder, a renal disease, dermatitis, HIV-related cachexia, cerebral malaria, ankylosing spondolytis, leprosy, anemia and fibromyalgia.

29. The method of claim 27, wherein the condition is selected from the group consisting of psoriasis, atopic dermatitis, rheumatoid arthritis, an inflammatory bowel disease, asthma and chronic obstructive pulmonary disease.

30. The method of claim 27, wherein the condition is psoriasis, said psoriasis is selected from the group consisting of plaque psoriasis, flexural psoriasis, Guttate psoriasis, pustular psoriasis, nail psoriasis and erythrodermic psoriasis.

31. The method of claim 30, wherein the psoriasis is selected from the group consisting of plaque psoriasis and nail psoriasis.

32. A method of inhibiting a phosphodiesterase (PDE), the method comprising:

contacting the phosphodiesterase with a compound of claim 1, thereby inhibiting the phosphodiesterase.

33. The method of claim 32, wherein said phosphodiesterase is selected from the group consisting of phosphodiesterase4 (PDE4) and phosphodiesterase7 (PDE7).

8. The compound of a preceding claim, wherein R^b is OR⁴, and R⁴ is selected from the group consisting of 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.

9. The compound of a preceding claim, wherein R^b is OR⁴, and R⁴ is substituted or unsubstituted alkyl.