Pegylated carfilzomib compounds

Patent metadata

Field	Value
Publication number	US-11077198-B2
Application number	US-202016857111-A
Country	US
Kind code	B2
Filing date	Apr 23, 2020
Priority date	May 24, 2016
Publication date	Aug 3, 2021
Grant date	Aug 3, 2021

Abstract

The present invention provides a method of treating multiple myeloma using polymeric pegylated carfilzomib compounds, and pharmaceutically acceptable salts thereof, of Formula I

wherein R 1 , R 2 , linker, PEG, n and o are as defined herein.

First claim

What is claimed is:

1. A process of making a compound having the structure

the process comprising the step of

wherein X— is a counter ion salt selected from the group consisting of a chloride anion, a bisulfate anion, a sulfate anion, a nitrate anion, a phosphate anion, an alky-sulfonate anion or an aryl-sulfonate anion; R 1 is C 1-10 alkyl or C 3-7 cycloalkyl; and PEG is a polyethylene glycol polymeric moiety having a molecular weight ranging from about 500 to about 20K.

2. The process of claim 1 , wherein R 1 is C 1-10 alkyl.

3. The process of claim 2 , wherein R 1 is methyl, ethyl, propyl, isopropyl, butyl, t-butyl, pentyl, hexyl or heptyl.

4. The process of claim 2 , wherein R 1 is methyl.

5. The process of claim 4 , wherein the PEG has a weight of 2K or 3K.

6. The process of claim 5 , wherein the PEG is linear PEG.

7. The process of claim 5 , wherein X— is an alky-sulfonate anion.

8. The process of claim 7 , wherein X— is mesylate.

9. The process of claim 4 , wherein X— is a chloride anion or an alky-sulfonate anion.

10. The process of claim 1 , wherein the PEG has a weight ranging from about 2K to about 20K.

11. The process of claim 10 , wherein the PEG is a linear PEG.

12. The process of claim 11 , wherein R 1 is methyl or ethyl and X— is a chloride anion or an alky-sulfonate anion.

13. The process of claim 12 , wherein R 1 is methyl.

14. The process of claim 10 , wherein the PEG has a weight of 2K, 3K, 5K or 20K.

15. The process of claim 10 , wherein the PEG has a weight of 2K, 3K, or 5K.

16. The process of claim 10 , wherein the PEG has a weight of 2K or 3K.

17. The process of claim 10 , wherein R 1 is methyl.

18. The process of claim 16 , wherein X— is a chloride anion or an alky-sulfonate anion.

19. The process of claim 10 , wherein R 1 is methyl or ethyl and X— is a chloride anion or an alky-sulfonate anion.

20. The process of claim 19 , wherein R 1 is methyl.

21. The process of claim 1 , wherein X— is a chloride anion or an alky-sulfonate anion.

22. The process of claim 21 , wherein R 1 is methyl and the PEG has a weight of 2K or 3K and the PEG is linear PEG.

23. The process of claim 21 , wherein the alky-sulfonate anion is mesylate.

24. The process of claim 21 , wherein the PEG has a weight ranging from about 2K to about 20K.

25. The process of claim 24 , wherein the PEG is linear PEG.

Assignees

• Amgen Inc

Inventors

• Luehr Gary
• Anik Shabbir T
• Peng Ge
• DOTSENKO Irina
• Phiasivongsa Pasit
• ROMANINI Dante

Classifications

• A61K47/60 Primary

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title

• C08G65/331

  containing oxygen {(cyclic ether compounds C08G65/26)} · CPC title

• C07K5/10

  Tetrapeptides · CPC title

• C07D413/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K38/07 Primary

  Tetrapeptides · CPC title