BTK INHIBITORS FOR THE TREATMENT OF IMMUNE MEDIATED CONDITIONS

• US 20120053189A1
• Filed: 06/28/2011
• Published: 03/01/2012
• Est. Priority Date: 06/28/2010
• Status: Abandoned Application

• Current Assignee: Pharmacyclics Incorporated (Abbvie Incorporated)
• Original Assignee: Pharmacyclics Incorporated (Abbvie Incorporated)
• Inventors: Loury, David J.
• Application Number:
  US13/171,304
• Publication Number:
  US 20120053189A1
• Time in Patent Office: Days
• US Class Current: 514/262.1
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• 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 27/02 Ophthalmic agents
• 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 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 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

Disclosed herein are pharmaceutical dosage forms of Brutons tyrosine kinase (Btk) inhibitors. Methods for the preparation of the compounds are disclosed. Methods of using the pharmaceutical dosage forms are disclosed for the treatment of immune mediated conditions and inflammatory diseases or conditions.

Claims

1. A pharmaceutical dosage form comprising from about 0.1 mg to about 40 mg of (E)-1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)-4-(dimethylamino)but-2-en-1-one or a pharmaceutically acceptable salt or solvate thereof.

2. The pharmaceutical dosage form of claim 1 comprising from about 0.1 mg to about 10 mg.

3. The pharmaceutical dosage form of claim 1 comprising from about 0.1 mg to about 5 mg.

4. The pharmaceutical dosage form of claim 1 comprising from about 0.5 mg to about 3.0 mg.

5. The pharmaceutical dosage form of any of claims 1 wherein the dosage form is suitable for once-a-day administration.

6. The pharmaceutical dosage form of any of claims 1 wherein the dosage form is suitable for oral administration.

7. The pharmaceutical dosage form of any of claims 1 further comprising a pharmaceutically acceptable carrier, excipient or binder.

8. A method for treating an immune-mediated disease or condition comprising administering to a subject in need thereof a therapeutically effective amount of from about 0.1 mg to about 40 mg of (E)-1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)-4-(dimethylamino)but-2-en-1-one or a pharmaceutically acceptable salt or solvate thereof.

9. The method of claim 8 wherein the therapeutically effective amount is from about 0.1 mg to about 10 mg.

10. The method of claim 8 wherein the therapeutically effective amount is from about 0.1 mg to about 5 mg.

11. The method of claim 8 wherein the total amount of (E)-1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)pyrrolidin-1-yl)-4-(dimethylamino)but-2-en-1-one is administered once a day.

12. The method of claim 8 wherein the immune-mediated disease or condition is inflammatory bowel conjunctivitis, allergic rhinitis, atopic dermatitis, or idiopathic thrombocytopenic purpura disease, arthritis, lupus, rheumatoid arthritis, psoriatic arthritis, osteoarthritis, Still'"'"'s disease, juvenile arthritis, diabetes, myasthenia gravis, Hashimoto'"'"'s thyroiditis, Ord'"'"'s thyroiditis, Graves'"'"' disease Sjö

gren'"'"'s syndrome, multiple sclerosis, Guillain-Barré

syndrome, acute disseminated encephalomyelitis, Addison'"'"'s disease, opsoclonus-myoclonus syndrome, ankylosing spondylitisis, antiphospholipid antibody syndrome, aplastic anemia, autoimmune hepatitis, coeliac disease, Goodpasture'"'"'s syndrome, idiopathic thrombocytopenic purpura, optic neuritis, scleroderma, primary biliary cirrhosis, Reiter'"'"'s syndrome, Takayasu'"'"'s arteritis, temporal arteritis, warm autoimmune hemolytic anemia, Wegener'"'"'s granulomatosis, psoriasis, alopecia universalis, Behç

et'"'"'s disease, chronic fatigue, dysautonomia, endometriosis, interstitial cystitis, neuromyotonia, scleroderma, or vulvodynia, graft versus host disease, transplantation, transfusion, anaphylaxis, allergy, allergy-related urticaria, type I hypersensitivity, allergic.

13. The method of claim 8 wherein the immune-mediated disease or condition is rheumatoid arthritis, lupus, inflammatory bowel disease, allergy, allergy-related urticaria, multiple sclerosis, diabetes, idiopathic thrombocytopenic purpura or transplantation.

14. The method of claim 8 wherein the immune-mediated disease or condition is rheumatoid arthritis.