2,2-difluoropropionamide derivatives of bardoxolone methyl, polymorphic forms and methods of use thereof

Patent metadata

Field	Value
Publication number	US-2018009839-A1
Application number	US-201715622568-A
Country	US
Kind code	A1
Filing date	Jun 14, 2017
Priority date	Apr 27, 2012
Publication date	Jan 11, 2018
Grant date	—

Abstract

The present invention relates generally to the compound:
N-((4aS,6aR,6bS,8aR,12aS,14aR,14bS)-11-cyano-2,2,6a,6b,9,9,12a-heptamethyl-10,14-dioxo-1,2,3,4,4a,5,6,6a,6b,7, 8,8a,9,10,12a,14,14a,14b-octadecahydropicen-4a-yl)-2,2-difluoropropanamide, polymorphic forms thereof, methods for preparation and use thereof, pharmaceutical compositions thereof, and kits and articles of manufacture thereof.

First claim

1 - 42 . (canceled)

43 . A method of treating or preventing a condition associated with inflammation or oxidative stress in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of a compound of the formula:

44 - 45 . (canceled)

46 . The method of claim 43 , wherein the condition is a cancer, inflammation, an autoimmune disease, inflammatory bowel disease, liver disease, pancreatitis, or diabetes.

47 - 58 . (canceled)

59 . The method of claim 46 , wherein the condition is an autoimmune disease.

60 . The method of claim 59 , wherein the condition is rheumatoid arthritis, lupus, Crohn's disease, or psoriasis.

61 - 95 . (canceled)

96 . The method of claim 46 , wherein the condition is cancer.

97 . The method of claim 96 , wherein the cancer is a carcinoma, sarcoma, lymphoma, leukemia, melanoma, mesothelioma, multiple myeloma, or seminoma.

98 . The method of claim 96 , wherein the cancer is of the bladder, blood, bone, brain, breast, central nervous system, cervix, colon, endometrium, esophagus, gall bladder, genitalia, genitourinary tract, head, kidney, larynx, liver, lung, muscle tissue, neck, oral or nasal mucosa, ovary, prostate, skin, spleen, small intestine, large intestine, stomach, testicle, or thyroid.

99 . A method for treating or preventing cancer in a patient in need thereof, comprising administering to the patient a combined effective amount of a compound of the formula:

and an immunotherapy.

100 . The method of claim 99 , wherein the immunotherapy is a cancer targeting immunotherapy, a dendritic cell-based immunotherapy, or an adoptive T-cell immunotherapy.

101 . The method of claim 100 , wherein the immunotherapy is a cancer targeting antibody which is preferably selected from trastuzumab, alemtuzumab, bevacizumab, cetuximab, panitumumab, ibritumomab tiuxetan, tositumomab, brentuximab vedotin, ado-trastuzumab emtansine, and denileukin dititox.

102 . The method of claim 99 , wherein the cancer is a carcinoma, sarcoma, lymphoma, leukemia, melanoma, mesothelioma, multiple myeloma, or seminoma.

103 . The method of claim 99 , wherein the cancer is of the bladder, blood, bone, brain, breast, central nervous system, cervix, colon, endometrium, esophagus, gall bladder, genitalia, genitourinary tract, head, kidney, larynx, liver, lung, muscle tissue, neck, oral or nasal mucosa, ovary, pancreas, prostate, skin, spleen, small intestine, large intestine, stomach, testicle, or thyroid.

104 . A method for treating or preventing a seizure disorder in a patient in need thereof, comprising administering to the patient an effective amount of a compound of the formula:

105 . The method of claim 104 , wherein the seizure disorder is epilepsy

106 . A method for treating or preventing a condition associated with oxidative stress caused by mitochondrial dysfunction in a patient in need thereof, comprising administering to the patient an effective amount of a compound of the formula:

Assignees

• Reata Pharmaceuticals Inc

Inventors

• Anderson Eric
• Liu Xiaofeng
• Decker Andrea

Classifications

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P39/06

  Free radical scavengers or antioxidants · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title