Synthesis of epothilones, intermediates thereto, analogues and uses thereof

• US 7,875,638 B2
• Filed: 06/09/2008
• Issued: 01/25/2011
• 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: Dorn, David, Chou, Ting-Chao, Gabarda, Ana E., Dong, Huajin, Yoshimura, Fumihiko, Rivkin, Alexey, Moore, Malcolm A. S., Wu, Kaida, Danishefsky, Samuel J.
• Primary Examiner(s): Saeed; Kamal A
• Application Number:
  US12/135,823
• Publication Number:
  US 20090149516A1
• Time in Patent Office: 960 Days
• Field of Search: None
• US Class Current: 514/365
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• 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:

2. The compound of claim 1 of the formula:

3. The compound of claim 2, wherein A-B is —

CH═

C(R_B)—

.

4. The compound of claim 2, wherein A-B is

5. The compound of claim 2 wherein R_B is methyl.

6. The compound of claim 2 wherein R_B is —

CF₃.

7. The compound of claim 2, wherein R₈ is methyl.

8. The compound of claim 2, wherein C-D is

9. The compound of claim 8, wherein Z is NH or CH₂.

10. The compound of claim 8, wherein Z is O.

11. The compound of claim 2, 3, or 4, wherein C-D is

12. The compound of claim 11, wherein Z is NH or CH₂.

13. The compound of claim 2, wherein Y is S.

14. The compound of claim 2, wherein Y is O.

15. The compound of claim 2, wherein C-D is —

C(R_C)₂—

C(R_D)₂—

.

16. The compound of claim 15, wherein each occurrence of R_C and R_D is selected from the group consisting of hydrogen, lower alkyl, hydroxyl, halogen, or lower alkoxy.

17. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable excipient.

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

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

20. A pharmaceutical composition comprising:

a therapeutically effective amount of a compound of claim 1, or pharmaceutically acceptable salts thereof; and

a pharmaceutically acceptable carrier or diluent,

wherein the therapeutically effective amount of the compound is an amount sufficient to deliver about 0.001 to about 40 mg compound per kg body weight of a subject.