INHIBITORS OF FATTY ACID AMIDE HYDROLASE

• US 20110224171A1
• Filed: 03/16/2011
• Published: 09/15/2011
• Est. Priority Date: 10/10/2006
• Status: Active Grant

• Current Assignee: Infinity Pharmaceuticals, Inc.
• Original Assignee: Infinity Pharmaceuticals, Inc.
• Inventors: Behnke, Mark L., Grogan, Michael J., Tibbitts, Thomas T., Snyder, Daniel A., Castro, Alfredo C., Adams, Julian, Liu, Tao, Evans, Catherine A., Grenier, Louis
• Granted Patent: US 8,329,675 B2
• Time in Patent Office: Days
• US Class Current: 514/64
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• 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 1/14 Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• 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 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 21/04 for myasthenia gravis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• 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 27/06 : Antiglaucoma agents or miotics
• 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 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/18 : for HIV
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 35/02 : specific for leukemia
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/14 : of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : 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
• CPC Class Codes: C07F 5/05 : Cyclic compounds having at least one ring containing boron but no carbon in the ring

Abstract

The present invention provide compounds, and pharmaceutical compositions thereof, encompassed by the formulae (I), (II) or (III).

The present invention also provides methods for treating an FAAH mediated disease, disorder or condition by administering a therapeutically effective amount of a provided compound of the formulae (I), (II) or (III), or a pharmaceutical composition thereof, to a patient in need thereof. Additionally, the present invention provides methods for inhibiting FAAH in a patient by administering a therapeutically effective amount of a compound of the formulae (I), (II) or (III), or a pharmaceutical composition thereof, to a patient in need thereof.

Claims

1-25. -25. (canceled)

26. A method for treating an FAAH-mediated disorder comprising administering to a subject having the FAAH-mediated disorder a therapeutically effective amount of a compound having the following formula:

27. The method of claim 26, wherein Z¹ and Z² are hydroxyl.

28. The method of claim 26, wherein m is 1 or 2.

29. The method of claim 26, wherein m is 1 and R² is meta to X.

30. The method of claim 26, wherein n is 1 or 2.

31. The method of claim 26, wherein n is 1 and R¹ is ortho to the boron atom.

32. The method of claim 26, wherein R¹ is halide.

33. The method of claim 26, wherein at least one of R¹ is fluoro and ortho to the boron atom.

34. The method of claim 26, wherein R² is halide.

35. The method of claim 26, wherein X is a bond.

36. The method of claim 26, wherein X is OCR⁴R⁵, SCR⁴R⁵, or O.

37. The method of claim 26, wherein the compound is:

38. The method of claim 26, wherein the compound has the following formula:

39. The method of claim 26, wherein the compound has the following formula:

40. The method of claim 26, wherein the compound has the following formula:

43. The method of claim 37, wherein the FAAH-mediated disorder is diabetic neuropathy.

44. The method of claim 37, wherein the FAAH-mediated disorder is fibromyalgia.

45. The method of claim 37, wherein the FAAH-mediated disorder is post-herpetic neuralgia.

46. The method of claim 38, wherein the FAAH-mediated disorder is diabetic neuropathy.

47. The method of claim 38, wherein the FAAH-mediated disorder is fibromyalgia.

48. The method of claim 38, wherein the FAAH-mediated disorder is post-herpetic neuralgia.

49. The method of claim 39, wherein the FAAH-mediated disorder is diabetic neuropathy.

50. The method of claim 39, wherein the FAAH-mediated disorder is fibromyalgia.

51. The method of claim 39, wherein the FAAH-mediated disorder is post-herpetic neuralgia.

52. The method of claim 40, wherein the FAAH-mediated disorder is diabetic neuropathy.

53. The method of claim 40, wherein the FAAH-mediated disorder is fibromyalgia.

54. The method of claim 40, wherein the FAAH-mediated disorder is post-herpetic neuralgia.