COMPOUNDS MODULATING C-KIT AND C-FMS ACTIVITY AND USES THEREFOR

• US 20110166174A1
• Filed: 12/01/2010
• Published: 07/07/2011
• Est. Priority Date: 05/17/2005
• Status: Abandoned Application

• Current Assignee: Plexxikon Inc (Daiichi Sankyo Company Limited)
• Original Assignee: Plexxikon Inc (Daiichi Sankyo Company Limited)
• Inventors: Bremer, Ryan, Zuckerman, Rebecca, Wu, Guoxian, Artis, Dean R., Zhu, Hongyao, Spevak, Wayne, Zhang, Jiazhong, Zhang, Chao, Ibrahim, Prabha N., Hurt, Clarence R.
• Application Number:
  US12/958,376
• Publication Number:
  US 20110166174A1
• Time in Patent Office: Days
• US Class Current: 514/300
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• 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 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 19/10 for osteoporosis
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 3/14 for calcium homeostasis vitamin D A61P3/02; parathyroid hormones A61P5/18; calcitonin A61P5/22; osteoporosis A61P19/10; bone metastasis A61P35/04
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• 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 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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: C07D 471/04 : Ortho-condensed systems

Abstract

Compounds active on the receptor protein tyrosine kinases c-kit and c-fms are provided herewith. Also provided herewith are compositions useful for treatment of c-kit mediated diseases or condition and c-fms-mediated diseases or condition, and methods for the use thereof.

Claims

1-35. -35. (canceled)

36. A method for treating a subject suffering from or at risk of a c-kit or c-fms mediated disease or condition, comprising administering to the subject an effective amount of a compound having the chemical structure:

39. The method of claim 36, wherein the compound is approved for administration to a human.

40. The method of claim 39, wherein the disease or condition is selected from the group consisting of mast cell tumors, small cell lung cancer, testicular cancer, gastrointestinal stromal tumors, glioblastoma, astrocytoma, neuroblastoma, carcinomas of the female genital tract, sarcomas of neuroectodermal origin, colorectal carcinoma, carcinoma in situ, Schwann cell neoplasia associated with neurofibromatosis, acute myeloid leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, multiple myeloma, mastocytosis, melanoma, breast cancer, ovarian cancer, canine mast cell tumors, hypertrophy, asthma, rheumatoid arthritis, allergic rhinitis, multiple sclerosis, inflammatory bowel syndrome, transplant rejection, systemic lupus erythematosis, Wegener'"'"'s granulomatosis, Chronic Obstructive Pulmonary Disease, emphysema, atherosclerosis, insulin resistance, hyperglycemia, lipolysis, hypereosinophilia, osteoporosis, increased risk of fracture, hypercalcemia, bone metastases, glomerulonephritis, interstitial nephritis, Lupus nephritis, tubular necrosis, and diabetes-associated renal complications.

43. The method of claim 36, wherein L¹ is CH₂.

44. The method of claim 36, wherein L² is selected from the group consisting of —

O—

CH₂—

, NH—

CH₂—

, —

NH—

CH(CH₃)— and

—

NH—

C(O).

45. The method of claim 36, wherein L¹ is CH₂ and L² is selected from the group consisting of —

O—

CH₂—

, NH—

CH₂—

, —

NH—

CH(CH₃)— and

—

NH—

C(O).

46. The method of claim 36, wherein Y₁ is CH and Y₂ is CR⁵.

47. The method of claim 46, wherein R⁵ is fluoro, chloro, lower alkyl or lower alkoxy.

48. The method of claim 46, wherein R⁵ is chloro or methoxy.

49. The method of claim 36, wherein Y₂ is CH and Y₁ is CR⁴.

50. The method of claim 49, wherein R⁴ is fluoro, chloro, lower alkyl or lower alkoxy.

51. The method of claim 49, wherein R⁴ is chloro or methoxy.

52. The method of claim 40, wherein the disease or condition is selected from the group consisting of mast cell tumors, small cell lung cancer, testicular cancer, gastrointestinal stromal tumors, glioblastoma, astrocytoma, neuroblastoma, carcinomas of the female genital tract, sarcomas of neuroectodermal origin, colorectal carcinoma, carcinoma in situ, Schwann cell neoplasia associated with neurofibromatosis, acute myeloid leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, multiple myeloma, mastocytosis, melanoma, breast cancer, ovarian cancer and canine mast cell tumors.

53. The method of claim 40, wherein the disease or condition is selected from the group consisting of hypertrophy, asthma, rheumatoid arthritis, allergic rhinitis, multiple sclerosis, inflammatory bowel syndrome, transplant rejection, systemic lupus erythematosis, Wegener'"'"'s granulomatosis, Chronic Obstructive Pulmonary Disease, emphysema, atherosclerosis, insulin resistance, hyperglycemia, lipolysis, hypereosinophilia, osteoporosis, increased risk of fracture, hypercalcemia, bone metastases, glomerulonephritis, interstitial nephritis, Lupus nephritis, tubular necrosis and diabetes-associated renal complications.

54. The method of claim 45, wherein the disease or condition is selected from the group consisting of mast cell tumors, small cell lung cancer, testicular cancer, gastrointestinal stromal tumors, glioblastoma, astrocytoma, neuroblastoma, carcinomas of the female genital tract, sarcomas of neuroectodermal origin, colorectal carcinoma, carcinoma in situ, Schwann cell neoplasia associated with neurofibromatosis, acute myeloid leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, multiple myeloma, mastocytosis, melanoma, breast cancer, ovarian cancer and canine mast cell tumors.

55. The method of claim 45, wherein the disease or condition is selected from the group consisting of hypertrophy, asthma, rheumatoid arthritis, allergic rhinitis, multiple sclerosis, inflammatory bowel syndrome, transplant rejection, systemic lupus erythematosis, Wegener'"'"'s granulomatosis, Chronic Obstructive Pulmonary Disease, emphysema, atherosclerosis, insulin resistance, hyperglycemia, lipolysis, hypereosinophilia, osteoporosis, increased risk of fracture, hypercalcemia, bone metastases, glomerulonephritis, interstitial nephritis, Lupus nephritis, tubular necrosis and diabetes-associated renal complications.

37-38. -38. (canceled)

41. (canceled)

42. A kit comprising a compound having the chemical structure:

56. The kit of claim 42, wherein the compound is approved for a medical indication selected from the group consisting of mast cell tumors, small cell lung cancer, testicular cancer, gastrointestinal stromal tumors, glioblastoma, astrocytoma, neuroblastoma, carcinomas of the female genital tract, sarcomas of neuroectodermal origin, colorectal carcinoma, carcinoma in situ, Schwann cell neoplasia associated with neurofibromatosis, acute myeloid leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, multiple myeloma, mastocytosis, melanoma, breast cancer, ovarian cancer and canine mast cell tumors.

57. The kit of claim 42, wherein the compound is approved for a medical indication selected from the group consisting of hypertrophy, asthma, rheumatoid arthritis, allergic rhinitis, multiple sclerosis, inflammatory bowel syndrome, transplant rejection, systemic lupus erythematosis, Wegener'"'"'s granulomatosis, Chronic Obstructive Pulmonary Disease, emphysema, atherosclerosis, insulin resistance, hyperglycemia, lipolysis, hypereosinophilia, osteoporosis, increased risk of fracture, hypercalcemia, bone metastases, glomerulonephritis, interstitial nephritis, Lupus nephritis, tubular necrosis, and diabetes-associated renal complications.