Proteasome inhibitors and processes for their preparation, purification and use

• US 8,541,590 B2
• Filed: 06/20/2012
• Issued: 09/24/2013
• Est. Priority Date: 12/22/2009
• Status: Expired due to Fees

• Current Assignee: Cephalon Incorporated (Teva Pharmaceutical Industries Limited)
• Original Assignee: Cephalon Incorporated (Teva Pharmaceutical Industries Limited)
• Inventors: Roemmele, Renee Caroline
• Primary Examiner(s): Andres, Janet
• Assistant Examiner(s): REESE, HEIDI L
• Application Number:
  US13/528,147
• Publication Number:
  US 20120270840A1
• Time in Patent Office: 461 Days
• Field of Search: None
• US Class Current: 546/314
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07F 5/02 Boron compounds
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds

Abstract

The invention provides boronic esters of Formula I

wherein R¹, R², R³, and R⁴ are as described herein, and methods for the preparation and purification thereof.

Claims

1. A boronic ester of Formula I

2. The boronic ester of claim 1, wherein the boronic ester is Formula IX

3. The boronic ester of claim 1, wherein the boronic ester is Formula X

4. The boronic ester of claim 1, wherein the boronic ester is Formula XI

5. A process for preparing a pharmaceutical composition, comprising the step of combining the boronic ester of any of claims 1-4 with a pharmaceutically acceptable carrier, diluent, or excipient.

6. A process for preparing a pharmaceutical composition of a boronic acid of Formula IA

7. The process of claim 6, wherein R¹ is 2-(6-phenyl)pyridinyl and R² is (1R)-1-hydroxyethyl.

8. The process of claim 6, wherein R¹ is 2-pyrazinyl and R² is benzyl.

9. A process for purifying a boronic acid of Formula IA

10. The process of claim 9, wherein R¹ is 2-(6-phenyl)pyridinyl and R² is (1R)-1-hydroxyethyl.

11. The process of claim 9, wherein R¹ is 2-pyrazinyl and R² is benzyl.

12. A process for preparing a boronic acid of Formula IA

13. The process of claim 12, wherein R¹ is 2-(6-phenyl)pyridinyl, R² is (1R)-1-hydroxyethyl, and R³ and R⁴ are H.

14. The process of claim 12, wherein R¹ is 2-(6-phenyl)pyridinyl, R² is (1R)-1-hydroxyethyl, and R³ and R⁴ are methyl.

15. The process of claim 12, wherein R¹ is 2-pyrazinyl, R² is benzyl, and R³ and R⁴ are H.