Boron-containing small molecules

• US 8,470,803 B2
• Filed: 09/10/2009
• Issued: 06/25/2013
• 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.
• Primary Examiner(s): Aulakh, Charanjit
• Application Number:
  US13/062,466
• Publication Number:
  US 20110166103A1
• Time in Patent Office: 1,384 Days
• Field of Search: 514/64, 546/13, 558/288
• 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, or a salt thereof, having a structure which is

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

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

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

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

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

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

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

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

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

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

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

15. The compound of claim 1, or a salt thereof, 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 claim 1, or a salt thereof, 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 claim 1, or a salt thereof, wherein R^b is NHR⁵, and R⁵ is substituted or unsubstituted heteroalkyl.

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

19. A pharmaceutical formulation comprising:

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

(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. The compound of claim 1, or a salt thereof, having a structure which is selected from the group consisting of

23. The compound of claim 1, or a salt thereof, wherein R^d is H or methyl or ethyl or propyl or isopropyl or butyl or isobutyl or secbutyl or t-butyl.

24. The compound of claim 1, or a salt thereof, wherein R^d is H.

25. The compound of claim 1, or a salt thereof, having a structure which is selected from the group consisting of

26. The compound of claim 1, or a salt thereof, wherein R^d is H or methyl or ethyl or propyl or isopropyl or butyl or isobutyl or secbutyl or t-butyl.

27. The compound of claim 1, or a salt thereof, wherein R^d is H.

28. The compound of claim 1, or a salt thereof, having a structure which is

29. The compound of claim 1, or a salt thereof, having a structure which is

30. The compound of claim 1, or a salt thereof, having a structure which is

31. The compound of claim 1, or a salt thereof, having a structure which is

32. The compound of claim 1, or a salt thereof, having a structure which is

33. The compound of claim 1, or a salt thereof, having a structure which is

34. The compound of claim 1, or a salt thereof, having a structure which is

35. The compound of claim 1, or a salt thereof, having a structure which is

36. The compound of claim 1, or a salt thereof, having a structure which is

37. The compound of claim 2, or a salt thereof, wherein R^b is OR⁴, and R⁴ is unsubstituted alkyl.

38. The compound of claim 2, or a salt thereof, wherein R^b is OR⁴, and R⁴ is unsubstituted C₁ or C₂ or C₃ alkyl.

39. The compound of claim 2, or a salt thereof, wherein R^b is OR⁴, and R⁴ is unsubstituted C₄ or C₅ or C₆ alkyl.

40. The compound of claim 2, or a salt thereof, wherein R^b is OR⁴, and R⁴ is alkyl substituted with one or two or three halogen.

41. The compound of claim 2, or a salt thereof, wherein R^b is —

O(CH₂)_m1OC(O)R^4d, wherein m1 is a number selected from 1 or 2 or 3 or 4 or 5 or 6 and R^4d is unsubstituted C₁ or C₂ or C₃ or C₄ or C₅ or C₆ alkyl.

42. The compound of claim 2, or a salt thereof, wherein R^b is —

O(CH₂)_m1C(O)R^4d, wherein m1 is a number selected from 1 or 2, or 3 or 4 or 5 or 6 and R^4d is unsubstituted C₁ or C₂ or C₃ or C₄ or C₅ or C₆ alkyl.

43. The compound of claim 2, or a salt thereof, wherein R^b is —

O(CH₂)_m1C(O)OR^4d, wherein m1 is a number selected from 1 or 2 or 3 or 4 or 5 or 6 and R^4d is H or unsubstituted.

44. The compound of claim 2, or a salt thereof, wherein R^b is —

O(CH₂)_m2C(O)NR^4eR^4f, wherein m2 is a number selected from 1 or 2 or 3 or 4 or 5 or 6, and R^4e is H or unsubstituted alkyl, R^4f is H or unsubstituted alkyl, or R^4e and R^4f, together with the nitrogen to which they are attached, are optionally joined to form a substituted or unsubstituted 4 to 8 membered ring.

45. The compound of claim 2, or a salt thereof, wherein R^b is OR⁴, wherein R⁴ is substituted or unsubstituted cycloalkyl.

46. The compound of claim 2, or a salt thereof, wherein R^b is OR⁴, wherein R⁴ is unsubstituted cyclopentyl or unsubstituted cyclohexyl.

47. The compound of claim 2, or a salt thereof, wherein R^b is OR⁴, wherein R⁴ is alkyl substituted with unsubstituted alkoxy.

48. The compound of claim 2, or a salt thereof, wherein R^b is —

O(CH₂)_m5OR³⁰, wherein m5 is 1 or 2 or 3 or 4 or 5 or 6 and R³⁰ is H or unsubstituted alkyl or unsubstituted tetrahydropyran.

49. The compound of claim 48, or a salt thereof, wherein R³⁰ is unsubstituted C₁ or C₂ or C₃ or C₄ or C₅ or C₆ alkyl.

50. The compound of claim 2, or a salt thereof, wherein R^b is —

C(O)R⁴, wherein R⁴ is H or unsubstituted C₁ or C₂ or C₃ or C₄ or C₅ or C₆ alkyl.

51. The compound of claim 2, or a salt thereof, wherein R^b is alkyl substituted with hydroxy.

52. The compound of claim 2, or a salt thereof, wherein R^b is alkyl substituted with carboxy or ester.

53. The compound of claim 2, or a salt thereof, wherein R^b is —

(CH₂)_m1C(O)OR^4a, wherein m1 is a number selected from 1 or 2 or 3 or 4 or 5 or 6 and R^4a is H or unsubstituted alkyl.

54. The compound of claim 2, or a salt thereof, wherein R^b is —

CH₂C(O)OR^4a, wherein R^4a is H or methyl or ethyl or t-butyl.

55. The compound of claim 2, or a salt thereof, wherein R^b is alkyl substituted with amino.

56. The compound of claim 2, or a salt thereof, wherein R^b is —

(CH₂)_m7NR^4aR^4b, wherein m7 is selected from the group consisting of 1, 2, 3, 4, 5 and 6 and R^4a is selected from the group consisting of H, unsubstituted alkyl and formyl, R^4b is selected from the group consisting of H, unsubstituted alkyl and formyl, or R^4a and R^4b, together with the nitrogen to which they are attached, are optionally joined to form a substituted or unsubstituted 4 to 8 membered ring.

57. The compound of claim 2, or a salt thereof, wherein R^b is selected from the group consisting of —

NH(CH₂)₂OH, —

NH(CH₂)₂OCH₃, —

NHCH₃, —

NHC(CH₃)₃, —

NH(CH₂)Ph, and —

NH(CH₂)₂O(CH₂)Ph.

58. The compound of claim 2, or a salt thereof, wherein R^b is selected from the group consisting of —

N(CH₃)₂, —

N(CH₃)(CH₂)₂OH, —

N(CH₃)(CH₂)₂OCH₃, —

NHCH₃, —

NHC(CH₃)₃, —

NH(CH₂)Ph, and —

NH(CH₂)₂O(CH₂)Ph.

59. The compound of claim 1, or a salt thereof,

having a structure which is

60. The compound of claim 1, or a salt thereof, having a structure which is

61. The compound of claim 1, or a salt thereof, having a structure which is

62. The compound of claim 1, or a salt thereof, having a structure which is

63. The compound of claim 1, or a salt thereof, having a structure which is

64. The compound of claim 1, or a salt thereof, having a structure which is

65. The compound of claim 1, or a salt thereof, having a structure which is

66. The compound of claim 1, or a salt thereof, having a structure which is