Epothilone derivatives

• US 7,125,899 B2
• Filed: 04/03/2003
• Issued: 10/24/2006
• Est. Priority Date: 07/08/1997
• Status: Expired due to Term

• Current Assignee: R-pharm us operating llc
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Vite, Gregory D., Johnson, James A., Borzilleri, Robert M., Kim, Soong-Hoon
• Primary Examiner(s): Kifle, Bruck
• Application Number:
  US10/405,886
• Publication Number:
  US 20030220295A1
• Time in Patent Office: 1,300 Days
• Field of Search: 514/63, 514/183, 514/365, 514/366, 514/450, 540/452, 540/462, 540/463, 540/468, 548/202, 548/203, 548/204, 549/346, 549/355
• US Class Current: 514/365
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 417/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 491/04 Ortho-condensed systems
• CPC Class Codes: C07D 491/044 with only one oxygen atom as ring hetero atom in the oxygen-containing ring
• CPC Class Codes: C07D 493/04 Ortho-condensed systems

Abstract

The present invention relates to epothilone derivatives, having the following formula:

in which the variables G, W, Q, X, Y, B₁, B₂, Z₁, Z₂, and R_1–R7 are defined herein, methods for preparation of the derivatives and intermediates thereof.

Claims

1. A compound having the formula V:

2. A method of treating cancer in a patient comprising administering to the patient a therapeutically-effective amount of the compound according to claim 1, and/or one or more hydrates, solvates, and/or isomers thereof, wherein the cancer is selected from one or more of cancer of the bladder, breast, colon, kidney, liver, lung, ovary, pancreas, stomach, cervix, thyroid, and/or prostate.

3. A method of treating breast cancer in a patient comprising administering to the patient a therapeutically-effective amount of the compound according to claim 1, and/or one or more hydrates, solvates, and/or isomers thereof.

4. A method of treating lung cancer in a patient comprising administering to the patient a therapeutically-effective amount of the compound according to claim 1, and/or one or more hydrates, solvates, and/or isomers thereof.

5. A pharmaceutical composition comprising the compound according to claim 1, and/or one or more hydrates, solvates, and/or isomers thereof, and one or more pharmaceutically-acceptable diluents, vehicles and/or additives.

6. A method of treating cancer in a patient comprising administering to the patient a therapeutically-effective amount of the pharmaceutical composition according to claim 5, wherein the cancer is selected from one or more of cancer of the bladder, breast, colon, kidney, liver, lung, ovary, pancreas, stomach, cervix, thyroid, and/or prostate.

18. The method of claim 2 comprising the treatment of prostate cancer.

19. The method of claim 2 comprising the treatment of kidney cancer.

20. The method of claim 2 comprising the treatment of pancreatic cancer.

7. A compound having the formula:

8. A solvate of the compound of claim 7.

9. A hydrate of the compound of claim 7.

10. A compound which is a geometric, optical or stereoisomer of the compound of claim 7, or a mixture comprising the compound of claim 7 and one or more geometric, optical and/or stereoisomers of the compound of claim 7.

11. A pharmaceutical composition comprising a solvate according to claim 8 and a pharmaceutically-acceptable diluent, vehicle, and/or additive.

12. A pharmaceutical composition comprising a hydrate according to claim 9 and a pharmaceutically-acceptable diluent, vehicle, and/or additive.

13. A pharmaceutical composition comprising a compound or mixture of compounds according to claim 10 and a pharmaceutically-acceptable diluent, vehicle, and/or additive.

14. A method of treating cancer in a patient comprising administering to the patient a therapeutically-effective amount of a pharmaceutical composition according to claim 11, wherein the cancer is selected from one or more of cancer of the bladder, breast, colon, kidney, liver, lung, ovary, pancreas, stomach, cervix, thyroid, and/or prostate.

15. A method of treating cancer in a patient comprising administering to the patient a therapeutically-effective amount of a pharmaceutical composition according to claim 12, wherein the cancer is selected from one or more of cancer of the bladder, breast, colon, kidney, liver, lung, ovary, pancreas, stomach, cervix, thyroid, and/or prostate.

16. A method of treating cancer in a patient comprising administering to the patient a therapeutically-effective amount of a pharmaceutical composition according to claim 13, wherein the cancer is selected from one or more of cancer of the bladder, breast, colon, kidney, liver, lung, ovary, pancreas, stomach, cervix, thyroid, and/or prostate.

17. The method of claim 16 comprising the treatment of breast cancer.