Synthesis of epothilones, intermediates thereto and analogues thereof

• US 6,921,769 B2
• Filed: 03/28/2003
• Issued: 07/26/2005
• Est. Priority Date: 08/23/2002
• Status: Expired due to Fees

• Current Assignee: Sloan-Kettering Institute For Cancer Research (Memorial Sloan-Kettering Cancer Center)
• Original Assignee: Sloan-Kettering Institute For Cancer Research (Memorial Sloan-Kettering Cancer Center)
• Inventors: Yoshimura, Fumikiko, Rivkin, Alexy, Danishefsky, Samuel J., Chou, Ting-Chao, Gabarda, Ana E.
• Primary Examiner(s): SAEED, KAMAL A
• Application Number:
  US10/402,004
• Publication Number:
  US 20040053995A1
• Time in Patent Office: 851 Days
• Field of Search: 514/365, 514/374, 548/203, 548/205, 548/235
• US Class Current: 514/365
• CPC Class Codes: C07D 417/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 493/04 Ortho-condensed systems

Abstract

The present invention provides compounds of formula (I):

• • as described generally and in classes and subclasses herein. The present invention additionally provides pharmaceutical compositions comprising compounds of formula (I) and provides methods of treating cancer comprising administering a compound of formula (I).

Claims

1. A compound of the formula:

wherein

X is O or NH;

Y is O or S;

R₅ and R ₆ are each independently hydrogen or a protecting group;

R₈ is independently —

CH₃, —

CH₂OH, —

CH₂SH, —

CH₂NH₂;

R_B is —

CF₃, —

CF₂H, or —

CFH₂; and

pharmaceutically acceptable salts thereof.

2. The compound of claim 1, wherein X is O.

3. The compound of claim 1, wherein X is NH.

4. The compound of claim 1, wherein Y is S.

5. The compound of claim 1, wherein Y is O.

6. The compound of claim 1, wherein X is O, and Y is S.

7. The compounds of claim 1, wherein X is O, and Y is O.

8. The compound of claim 1, wherein R_B is —

CF₃.

9. The compound of claim 1, wherein X is O, Y is S, and R_B is —

CF₃.

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

CF₂H.

11. The compound of claim 1, wherein R_B is —

CFH₂.

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

CH₃.

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

CH₂OH.

14. The compound of claim 1, wherein each of R₅ and R₆ is hydrogen.

17. A pharmaceutical composition comprising a compound of any one of claims 1-16 and a pharmaceutically acceptable excipient.

18. The pharmaceutical composition of claim 17 further comprising Cremophor.

19. The pharmaceutical composition of claim 17 further comprising Cremophor and ethanol.

20. The pharmaceutical composition of claim 17 further comprising an additional cytotoxic agent.

15. A compound of the formula:

16. A compound of the formula: