Crystalline peptide epoxyketone immunoproteasome inhibitor

• US 8,697,646 B2
• Filed: 04/06/2011
• Issued: 04/15/2014
• Est. Priority Date: 04/07/2010
• Status: Expired due to Fees

• Current Assignee: Onyx Therapeutics, Inc. (Amgen Inc.)
• Original Assignee: Onyx Therapeutics, Inc. (Amgen Inc.)
• Inventors: Phiasivongsa, Pasit
• Primary Examiner(s): Cordero Garcia, Marcela M
• Assistant Examiner(s): YANG, KAIPEEN E
• Application Number:
  US13/639,087
• Publication Number:
  US 20130065827A1
• Time in Patent Office: 1,105 Days
• Field of Search: None
• US Class Current: 514/6.9
• 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 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 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 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 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• 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: C07K 5/0806 the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala

Abstract

The invention relates to crystalline peptide keto epoxide compounds, methods of their preparation, and related pharmaceutical compositions.

Claims

1. A method for preparing a crystalline compound of Formula (II)

2. The method of claim 1, wherein the organic solvent is selected from acetonitrile, acetone, diethyl ether, diisopropyl ether, ethyl acetate, heptanes, isopropyl acetate, methanol, methyl tert-butyl ether, tetrahydrofuran, toluene, or any combination thereof.

3. The method of claim 2, wherein the organic solvent is selected from toluene, methyl tert-butyl ether, heptanes, or a combination thereof.

4. The method of claim 1, wherein bringing the solution to supersaturation comprises addition of an anti-solvent, allowing the solution to cool, reducing the volume of the solution, or any combination thereof.

5. The method of claim 4, wherein bringing the solution to supersaturation comprises cooling the solution to ambient temperature and reducing the volume of the solution.

6. The method of claim 1, further comprising washing the crystals.

7. The method of claim 6, wherein the washing comprises washing with a liquid selected from anti-solvent, acetonitrile, acetone, diethyl ether, diisopropyl ether, ethanol, ethyl acetate, heptanes, isopropyl acetate, methanol, methyl tert-butyl ether, tetrahydrofuran, toluene, or any combination thereof, or a combination thereof.

8. The method of claim 6, wherein washing comprises washing with a combination toluene and methyl tert-butyl ether.

9. The method of claim 7, wherein washing comprises washing with toluene.

10. The method of claim 1, wherein isolating the crystals comprises filtering the crystals.

11. The method of claim 1, further comprising drying the crystals under reduced pressure.

12. The method of claim 1, wherein the crystalline compound of Formula (II) is a solvate.

13. The method of claim 12, wherein the crystalline compound of Formula (II) is a toluene solvate.

14. A crystalline compound having a structure of Formula (II)

15. The crystalline compound of claim 14, having a DSC thermogram as shown in FIG. 1.

16. The crystalline compound of claim 14, having an XRPD pattern as shown in FIG. 2.

17. The crystalline compound of claim 14, which is a solvate.

18. The crystalline compound of claim 17, which is a toluene solvate.

19. A method for treating a disease or condition selected from an immune-related disease, cancer, inflammation, infection, proliferative disease, or neurodegenerative disease, comprising administering a crystalline compound of claim 14.

20. The method of claim 19, wherein the disease or condition is an immune-related disease.

21. The method of claim 20, wherein the immune-related disease is selected from autoimmune disease, Crohn'"'"'s disease, diabetes, lupus, multiple sclerosis, myositis, psoriasis, rheumatoid arthritis and ulcerative colitis.

22. The method of claim 19, wherein the disease or condition is cancer.

23. The method of claim 22, wherein the cancer is selected from leukemia, lymphoma and multiple myeloma.

24. The method of claim 19, wherein the disease or condition is inflammation.

25. The method of claim 19, wherein the disease or condition is an infection.

26. The method of claim 19, wherein the disease or condition is a proliferative disease.

27. The method of claim 19, wherein the disease or condition is a neurodegenerative disease.