Boron-containing small molecules as anti-inflammatory agents

• US 9,416,146 B2
• Filed: 03/23/2015
• Issued: 08/16/2016
• Est. Priority Date: 03/06/2008
• Status: Active Grant

• Current Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Original Assignee: Anacor Pharmaceuticals, Inc. (Pfizer Inc.)
• Inventors: Akama, Tsutomu
• Primary Examiner(s): Aulakh, Charanjit
• Application Number:
  US14/666,075
• Publication Number:
  US 20150291629A1
• Time in Patent Office: 512 Days
• Field of Search: 546/13, 558/288, 514/64
• US Class Current: 1/1
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• 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 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds
• CPC Class Codes: C07F 5/04 Esters of boric acids
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Compounds and methods of treating anti-inflammatory conditions are disclosed.

Claims

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

2. The compound of claim 1, or a salt thereof, wherein the compound has a formula which is a member selected from:

3. The compound of claim 1, or a salt thereof, wherein the compound has a formula which is a member selected from:

4. The compound of claim 1, or a salt thereof, wherein the compound has a formula which is a member selected from:

5. The compound of claim 4, or a salt thereof, wherein the compound is

6. The compound of claim 1, or a salt thereof, wherein the compound has a formula which is a member selected from:

7. The compound of claim 6, or a salt thereof, wherein R³ is methyl or C₂ alkyl or C₃ alkyl.

8. The compound of claim 6, or a salt thereof, wherein R³ is C₄ alkyl or C₅ alkyl or C₆ alkyl.

9. The compound of claim 7, or a salt thereof, wherein R^b is OR⁴, and R⁴ is unsubstituted C₁-C₆ straight chain or branched chain alkyl.

10. The compound of claim 9, or a salt thereof, wherein R⁴ is unsubstituted C₁ or C₂ or C₃ straight chain or branched chain alkyl.

11. The compound of claim 9, or a salt thereof, wherein the compound is

12. The compound of claim 9, or a salt thereof, wherein the compound is

13. The compound of claim 9, or a salt thereof, wherein the compound is

14. The compound of claim 9, or a salt thereof, wherein the compound is

15. The compound of claim 1, or a salt thereof, wherein the compound is

16. The compound of claim 1, or a salt thereof, wherein the compound is

17. The compound of claim 16, or a salt thereof, wherein the salt is a pharmaceutically acceptable salt.

18. The compound of claim 9, or a salt thereof, wherein R⁴ is unsubstituted C₄ or C₅ or C₆ alkyl.

19. The compound of claim 9, or a salt thereof, wherein R⁴ is methyl or ethyl or propyl or isopropyl or isobutyl.

20. The compound of claim 1, or a salt thereof, wherein R^b is OR⁴, and R⁴ is straight chain or branched chain alkyl substituted with unsubstituted cycloalkyl.

21. The compound of claim 1, or a salt thereof, wherein R^b is OR⁴, and R⁴ is

22. The compound of claim 1, or a salt thereof, wherein the compound is

23. The compound of claim 1, or a salt thereof, wherein R^b is OR⁴, and R⁴ is unsubstituted cycloalkyl.

24. The compound of claim 1, or a salt thereof, wherein R^b is OR⁴, and R⁴ is cyclopentyl or cyclohexyl.

25. The compound of claim 1, or a salt thereof, wherein the compound is

26. A pharmaceutical formulation comprising:

(a) the compound of claim 1, or a pharmaceutically acceptable salt thereof; and

(b) a pharmaceutically acceptable excipient.

27. The formulation of claim 26, wherein the compound is

28. The formulation of claim 26, which is a topical formulation.

29. The formulation of claim 26, wherein the formulation is a lotion or cream or foam or gel or ointment.

30. A method of treating a condition in an animal in need of the treatment, the method comprising administering to the animal a therapeutically effective amount of the compound of claim 1, or a pharmaceutically acceptable salt thereof, thereby treating the condition, wherein said condition is psoriasis or dermatitis.

31. The method of claim 30, wherein the compound is

32. The method of claim 31, wherein the condition is psoriasis.

33. The method of claim 31, wherein the condition is psoriasis, and said psoriasis is plaque psoriasis.

34. The method of claim 31, wherein the condition is psoriasis, and said psoriasis is flexural psoriasis.

35. The method of claim 31, wherein the condition is psoriasis, and said psoriasis is guttate psoriasis.

36. The method of claim 31, wherein the condition is psoriasis, and said psoriasis is pustular psoriasis.

37. The method of claim 31, wherein the condition is psoriasis, and said psoriasis is nail psoriasis.

38. The method of claim 31, wherein the condition is psoriasis, and said psoriasis is psoriatic arthritis.

39. The method of claim 31, wherein the condition is psoriasis, and said psoriasis is erythrodermic psoriasis.

40. The method of claim 31, wherein the condition is dermatitis.

41. The method of claim 31, wherein the condition is dermatitis, and said dermatitis is contact dermatitis.

42. The method of claim 31, wherein the condition is dermatitis, and said dermatitis is atopic dermatitis.

43. The method of claim 31, wherein the condition is dermatitis, and said dermatitis is eczema.