Boronate ester compounds and pharmaceutical compositions thereof

• US 9,175,017 B2
• Filed: 08/01/2014
• Issued: 11/03/2015
• Est. Priority Date: 06/17/2008
• Status: Active Grant

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Millennium Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Inventors: Elliott, Eric L., Ferdous, Abu J., Kaufman, Michael J., Komar, Sonja A., Mazaik, Debra L., McCubbin, Quentin J., Nguyen, Phuong M., Palaniappan, Vaithianathan, Skwierczynski, Raymond D., Truong, Nobel T., Varga, Csanad M., Zawaneh, Peter N.
• Primary Examiner(s): SHIAO, REI TSANG
• Application Number:
  US14/449,275
• Publication Number:
  US 20140349966A1
• Time in Patent Office: 459 Days
• Field of Search: 514/19.3
• US Class Current: 1/1
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• 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 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• 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 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• 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 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• 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 35/04 : specific for metastasis
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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: C07C 233/83 : of an acyclic saturated carbon skeleton
• CPC Class Codes: C07F 5/025 : Boronic and borinic acid compounds
• CPC Class Codes: C07F 5/04 : Esters of boric acids
• CPC Class Codes: C07K 5/06139 : with the first amino acid being heterocyclic
• CPC Class Codes: C07K 5/06191 : containing heteroatoms different from O, S, or N

Abstract

The present invention provides novel compounds useful as proteasome inhibitors. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.

Claims

1. A method for treating cancer, the method comprises administering to a patient in need of such treatment a therapeutically effective amount of a compound of formula (II):

2. The method of claim 1, wherein the compound of formula (II) is characterized by formula (III):

3. The method of claim 1, wherein the compound of formula (II) is characterized by formula (IV):

4. The method of claim 1, wherein the compound of formula (II) is characterized by formula (IIIa):

5. The method of claim 1, wherein the compound of formula (II) is characterized by formula (IVa):

6. The method of claim 1, wherein the patient in need of the treatment is a patient having or at risk of developing or experiencing a recurrence in a cancer selected from multiple myeloma and lymphoma.

7. The method according to any one of claims 1-6, wherein the compound of formula (II) is administered with another therapeutic agent.

8. The method of claim 7, wherein the other therapeutic agent is melphalan.

9. The method of claim 7, wherein the other therapeutic agent is lenalidomide.

10. The method of claim 1, wherein the compound or pharmaceutical composition is administered orally, parenterally, by inhalation spray, topically, rectally, nasally, buccally, vaginally, or via an implanted reservoir.

11. The method of claim 10, wherein the compound is administered orally.

12. The method of claim 10, wherein the compound is administered intravenously.

13. The method of claim 10, wherein the compound is administered systemically or locally.