Fluorinated esters of rapamycin

• US 5,100,883 A
• Filed: 04/08/1991
• Issued: 03/31/1992
• Est. Priority Date: 04/08/1991
• Status: Expired due to Term

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: American Home Products Corporation (Pfizer Inc.)
• Inventors: Schiehser, Guy A.
• Primary Examiner(s): BOND, ROBERT
• Application Number:
  US07/682,793
• Time in Patent Office: 358 Days
• Field of Search: 540/456, 514/183, 514/321
• US Class Current: 514/183
• CPC Class Codes: C07D 498/18 Bridged systems

Abstract

A compound of the structure ##STR1## wherein R¹ and R² are each, independently, hydrogen or ##STR2## R³ is a mono-, di-, poly-, or per-fluorinated alkyl group with the proviso that R¹ and R² are both not hydrogen, which by virtue of its immunosuppressive activity is useful in treating transplantation rejection, host vs. graft disease, autoimmune diseases and diseases of inflammation; by virtue of its antitumor activity is useful in treating solid tumors; and by virtue of its antifungal activity is useful in treating fungal infections.

Claims

1. A compound of the formula ##STR6## wherein R¹ and R² are each, independently, hydrogen or ##STR7## R³ is a mono-, di-, poly-, or per-fluorinated alkyl group of 1-10 carbon atoms;

with the proviso that R¹ and R² are both not hydrogen.

2. A compound of claim 1 where R² is hydrogen.

3. A compound of claim 1 where R³ is a mono-, di-, poly-, or per-fluorinated alkyl group of 1-6 carbon atoms.

4. A compound of claim 1 where R² is hydrogen and R³ is a mono-, di-, poly-, or per-fluorinated alkyl group of 1-6 carbon atoms.

5. A compound of claim 1 which is rapamycin, 42-ester with trifluoroacetic acid.

6. A compound of claim 1 which is rapamycin, 42-ester with 2,3,3,3-tetrafluoropropanoic acid.

7. A compound of claim 1 which is rapamycin, 42-ester with difluoroacetic acid.

8. A compound of claim 1 which is rapamycin, 42-ester with pentafluoropropionic acid.

10. A pharmaceutical composition for use as an immunosuppressive agent comprising an immunosuppressive amount of a compound of claim 1.

11. A composition as claimed in claim 10 in unit dosage form.

9. A method of treating transplantation rejection, host vs. draft disease, autoimmune diseases, and diseases of inflammation in a mammal by administering an effective amount of a compound having the formula ##STR8## wherein R¹ and R² are each, independently, hydrogen or ##STR9## R³ is a mono-, di-, poly-, or per-fluorinated alkyl group of 1-10 carbon atoms;

with the proviso that R¹ and R² are both not hydrogen.