Water soluble SDZ RAD esters

• US 6,331,547 B1
• Filed: 08/16/2000
• Issued: 12/18/2001
• Est. Priority Date: 08/18/1999
• Status: Expired due to Fees

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: American Home Products Corporation (Pfizer Inc.)
• Inventors: Zhu, Tianmin, Shah, Syed M., Saunders, Richard W.
• Primary Examiner(s): Kifle, Bruck
• Application Number:
  US09/639,610
• Time in Patent Office: 489 Days
• Field of Search: 514/291, 540/456
• US Class Current: 514/291
• CPC Class Codes: C07D 498/18 Bridged systems

Abstract

This invention provides novel water soluble pegylated esters of rapamycin, having the general structure:

wherein n is an integer from about 5 to about 450, as well as pharmaceutical compositions containing these compounds and methods for their use as immunosuppressive, anti-inflammatory, antifungal, antiproliferative and antitumor agents.

Claims

1. A compound of the structure

wherein n is an integer from 5-450.

2. The compound of claim 1 wherein n=5-200.

3. The compound of claim 1 wherein n=8-135.

4. The compound of claim 1 wherein n=8-20.

5. The compound of claim 1 wherein n=90-120.

6. The compound of claim 1 which is SDZ-RAD-PEG 5000 conjugate.

7. A method of treating transplantation rejection or graft vs. host disease in a mammal in need thereof, which comprises administering to said mammal an antirejection effective amount of a compound of the structure

wherein n is an integer from 5-450.

8. A method of treating a fungal infection in a mammal in need thereof, which comprises administering to said mammal an antifungal effective amount of a compound of the structure

wherein n is an integer from 5-450.

9. A method of treating rheumatoid arthritis in a mammal in need thereof, which comprises administering to said mammal an antiarthritis effective amount of a compound of the structure

wherein n is an integer from 5-450.

10. A method of treating restenosis in a mammal in need thereof, which comprises administering to said mammal an antiproliferative effective amount of a compound of the structure

wherein n is an integer from 5-450.

11. A method of treating pulmonary inflammation in a mammal in need thereof, which comprises administering to said mammal an antiinflammatory effective amount of a compound of the structure

wherein n is an integer from 5-450.

12. A pharmaceutical composition which comprises a compound of the structure

wherein n is an integer from 5-450, and a pharmaceutically acceptable carrier or excipient.

13. The pharmaceutical composition of claim 12 wherein n=8-200.

14. The pharmaceutical composition of claim 12 wherein n=8-135.

15. The pharmaceutical composition of claim 12 wherein n=8-20.

16. The pharmaceutical composition of claim 12 wherein n=90-120.

17. The pharmaceutical composition of claim 12 which is SDZ-RAD-PEG 5000 conjugate.

18. A method of treating glioblastoma in a mammal in need thereof, which comprises administering to said mammal an effective amount of a compound of the structure

wherein n is an integer from 5-450.