Trioxacarcins and uses thereof

• US 9,102,697 B2
• Filed: 03/22/2011
• Issued: 08/11/2015
• 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., Hill, Nicholas E., Svenda, Jakub, Yu, Robert T., Smaltz, Daniel J., Magauer, Thomas
• Primary Examiner(s): McIntosh, III, Traviss C
• Application Number:
  US13/636,263
• Publication Number:
  US 20130150314A1
• Time in Patent Office: 1,603 Days
• Field of Search: None
• US Class Current: 1/1
• 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 formula:

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

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

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

OR^D1.

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

OR^E1.

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

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

10. The compound of claim 1, wherein R⁸ is —

OR^H1.

11. The compound of claim 10, wherein R^H1 is hydrogen, a carbohydrate, or C_1-6 alkyl.

12. The compound of claim 11, wherein the carbohydrate is:

13. The compound of claim 1, wherein R⁹ is —

CH(OR^I3)₂; and

each occurrence of R^I3 is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a carbohydrate.

14. The compound of claim 1, wherein R¹ is ═

O.

15. The compound of claim 6, wherein R^D1 is C_1-6alkyl.

16. The compound of claim 7, wherein R^E1 is hydrogen.

17. The compound of claim 13, wherein R⁹ is —

CH(OCH₃)₂.

18. The compound of claim 1, wherein the compound is:

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

20. 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.