Compounds, compositions and methods of agelastatin alkaloids

• US 9,962,383 B2
• Filed: 09/02/2016
• Issued: 05/08/2018
• Est. Priority Date: 09/19/2013
• Status: Active Grant

• Current Assignee: Board of Trustees of The University of Illinois, Massachusetts Institute of Technology
• Original Assignee: Board of Trustees of The University of Illinois, Massachusetts Institute of Technology
• Inventors: Movassaghi, Mohammad, Hergenrother, Paul J.
• Primary Examiner(s): West, Theodore R.
• Application Number:
  US15/255,224
• Publication Number:
  US 20170143708A1
• Time in Patent Office: 613 Days
• CPC Class Codes: A61K 31/498 Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
• CPC Class Codes: A61K 31/4985 Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: C07D 487/14 Ortho-condensed systems

Abstract

The present invention, among other things, provides compounds, compositions and methods for treatment of cancer. In some embodiments, the present invention provides methods for treating blood cancer using agelastatin alkaloids.

Claims

1. A method for treating a cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of formula I:

2. The method of claim 1, wherein R¹ is —

CH₃.

3. The method of claim 1, wherein R² is —

OH.

4. The method of claim 1, wherein R³ is —

H.

5. The method of claim 1, wherein R⁴ is —

Br when R¹ is —

CH₃.

6. The method of claim 1, wherein the compound is

7. The method of claim 1, wherein the compound is

8. The method of claim 1, wherein the compound is

9. The method of claim 1, wherein the compound of formula I has no or low hemolytic activity at about 300 μ

M.

10. The method of claim 1, wherein the compound of formula I causes less than about 10% hemolysis two hours after administration at about 300 μ

M.

11. The method of claim 1, wherein the compound of formula I does not affect tubulin dynamics within cells.

12. The method of claim 1, wherein the compound of formula I is administered in a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof.

13. The method of claim 12, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier.

14. A method for treating blood cancer in a subject in need thereof, comprising administering to the subject a compound of formula I:

15. A method for treating a cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of formula I:

16. The method of claim 15, wherein R¹ is —

CH₃.

17. The method of claim 15, wherein R² is —

OH.

18. The method of claim 15, wherein R³ is —

H.

19. The method of claim 15, wherein R⁴ is —

Br when R¹ is —

CH₃.

20. The method of claim 15, wherein the compound is

21. The method of claim 15, wherein the compound is

22. The method of claim 15, wherein the compound is

23. The method of claim 15, wherein the compound of formula I has no or low hemolytic activity at about 300 μ

M.

24. The method of claim 15, wherein the compound of formula I causes less than about 10% hemolysis two hours after administration at about 300 μ

M.

25. The method of claim 15, wherein the compound of formula I does not affect tubulin dynamics within cells.

26. The method of claim 15, wherein the compound of formula I is administered in a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof.

27. The method of claim 26, wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier.