TRIOXACARCINS AND USES THEREOF

• US 20130150314A1
• Filed: 03/22/2011
• Published: 06/13/2013
• Est. Priority Date: 03/22/2010
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Myers, Andrew G., Svenda, Jakub, Hill, Nicholas E., Yu, Robert T., Smaltz, Daniel J., Magauer, Thomas
• Granted Patent: US 9,102,697 B2
• Time in Patent Office: Days
• US Class Current: 514/27
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 493/22 in which the condensed system contains four or more hetero rings
• CPC Class Codes: C07H 15/24 Condensed ring systems having three or more rings
• CPC Class Codes: C07H 15/26 Acyclic or carbocyclic radicals, substituted by hetero rings
• CPC Class Codes: C07H 17/04 Heterocyclic radicals containing only oxygen as ring hetero atoms

Abstract

The present invention relates to trioxacarcin compounds of the formula: (I) or pharmaceutically acceptable forms thereof; wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are as defined herein. The present invention also provides processes for preparing such compounds and intermediates thereto; pharmaceutical compositions comprising such compounds; and methods of use and treatment.

Claims

1. A compound of the Formula (I):

2. The compound of claim 1, wherein the compound is of the formula:

3. The compound of claim 2, wherein the compound is of the formula:

4. The compound of claim 2, wherein the compound is of formula:

5. The compound of claim 1, wherein the compound is of the formula:

6. The compound of claim 1, wherein R¹ is hydrogen.

7. The compound of claim 1, wherein R¹ is —

OR^A1.

8. The compound of claim 7, wherein R^A1 is a carbohydrate.

9. The compound of claim 8, wherein the carbohydrate is:

11. The compound of claim 1, wherein R² is hydrogen.

12. The compound of claim 1, wherein R³ is hydrogen.

13. The compound of claim 1, wherein R³ is —

OR^Cl.

16. The compound of claim 1, wherein R¹, R², and R³ are hydrogen.

17. The compound of claim 1, wherein R⁴ is —

OR^D1.

20. The compound of claim 1, wherein R⁵ is —

OR^E1.

22. The compound of claim 1, wherein R⁶ is C_1-6 alkyl.

24. The compound of claim 1, wherein R⁷ is hydrogen.

27. The compound of claim 1, wherein R⁸ is OR^H1.

28. The compound of claim 27, wherein R^H1 is a carbohydrate or C_1-6 alkyl.

29. The compound of claim 28, wherein the carbohydrate is:

32. The compound of claim 1, wherein R⁹ is CH(OR^I3)₂.

47. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable form thereof, and a pharmaceutically acceptable excipient.

48. A method of treating a disease, disorder or condition selected from the group consisting of proliferative diseases, diabetic retinopathy, inflammatory diseases, autoimmune diseases, and infectious diseases, comprising administering to a subject an effective amount of a compound of claim 1 or pharmaceutically acceptable form thereof.

10. (canceled)

14-15. -15. (canceled)

18-19. -19. (canceled)

21. (canceled)

23. (canceled)

25-26. -26. (canceled)

30-31. -31. (canceled)

33-46. -46. (canceled)

49-51. -51. (canceled)