Pyrrolo[2,3-b]pyridin-4-yl-amines and pyrrolo[2,3-b]pyrimidin-5-yl-amines as janus kinase inhibitors

• US 20110086835A1
• Filed: 10/30/2007
• Published: 04/14/2011
• Est. Priority Date: 12/22/2004
• Status: Active Grant

• Current Assignee: Incyte Holdings Corporation And Incyte Corporation
• Original Assignee: Incyte Corporation
• Inventors: Sparks, Richard B., Combs, Andrew P., Wang, Haisheng, Rodgers, James D.
• Granted Patent: US 8,053,433 B2
• Time in Patent Office: Days
• US Class Current: 514/210.18
• 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 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 25/00 Drugs for disorders of the nervous system
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• 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: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

The present invention provides pyrrolo[2,3-b]pyridine-4-yl amines pyrrolo[2,3-b]pyrimidin-4-yl amines that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases and cancer.

Claims

1-33. -33. (canceled)

34. A method of inhibiting an activity of JAK comprising contacting said JAK with a compound of Formula I:

35-40. -40. (canceled)

41. A method of treating a disease in a patient, wherein said disease is associated with JAK activity, comprising administering to said patient a therapeutically effective amount of a compound of Formula I:

42. The method of claim 41 wherein said disease is allograft rejection or graft versus host disease.

43. The method of claim 41 wherein said disease is an autoimmune disease.

44. The method of claim 43 wherein said autoimmune disease is a skin disorder, multiple sclerosis, rheumatoid arthritis, juvenile arthritis, type I diabetes, lupus, psoriasis, inflammatory bowel disease, Crohn'"'"'s disease, or autoimmune thyroid disorder.

45. The method of claim 41 wherein said disease is a viral disease.

46. The method of claim 45 wherein said viral disease is Epstein Barr Virus (EBV), Hepatitis B, Hepatitis C, HIV, HTLV 1, Varicell-Zoster Virus (VZV) or Human Papilloma Virus (HPV).

47. The method of claim 41 wherein said disease is cancer.

48. The method of claim 47 wherein said cancer is prostate cancer, lymphoma, leukemia, or multiple myeloma.

49. The method of claim 47 wherein said cancer is multiple myeloma.

50-54. -54. (canceled)

55. A method of treating a skin disorder in a patient comprising topically administering to said patient a therapeutically effective amount of a compound of Formula II:

56. The method of claim 55 wherein said skin disorder is atopic dermatitis or psoriasis.

57. The method of claim 55 wherein said skin disorder is skin sensitization, skin irritation, skin rash, contact dermatitis or allergic contact sensitization.

58. The method of claim 55 wherein said compound of Formula II is administered in the form of a transdermal patch, ointment, lotion, cream, or gel.

59. The method of claim 55 wherein A is CR¹.

60. The method of claim 55 wherein A is N.

61. A method of treating cancer in a patient comprising administering to said patient a therapeutically effective amount of a compound of Formula I:

62. The method of claim 61 wherein said cancer is prostate cancer, lymphoma, leukemia, or multiple myeloma.

63. The method of claim 61 wherein R¹ is H.

64. The method of claim 61 wherein R² is H.

65. The method of claim 61 wherein R³ is H.

66. The method of claim 61 wherein R⁴ is H or C_1-4 alkyl.

67. The method of claim 61 wherein R⁵ is 6-membered heterocycloalkyl substituted by one R⁶ and 0, 1 or 2 R⁷.

68. The method of claim 61 wherein R⁵ is piperidin-3-yl substituted by one R⁶ and 0, 1 or 2 R⁷.

69. The method of claim 61 wherein R⁵ is -L-pyrrolidin-2-yl;

L is C_1-4 alkylenyl and said pyrrolidin-2-yl is substituted by one R⁶ and 0, 1 or 2 R⁷.