Water soluble rapamycin esters

• US 5,780,462 A
• Filed: 12/11/1996
• Issued: 07/14/1998
• Est. Priority Date: 12/27/1995
• Status: Expired due to Term

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: American Home Products Corporation (Pfizer Inc.)
• Inventors: Zhu, Tianmin, Lee, Hyuk-Koo
• Primary Examiner(s): Daus, Donald G.
• Application Number:
  US08/763,768
• Time in Patent Office: 580 Days
• Field of Search: 514/183, 540/456
• US Class Current: 514/183
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/10 Antimycotics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07D 498/16 Peri-condensed systems
• CPC Class Codes: C07D 498/18 Bridged systems
• CPC Class Codes: C08G 65/329 with organic compounds

Abstract

A compound of the structure ##STR1## wherein R¹ and R² are each, independently, hydrogen or

COCH₂ --S--CH₂ CH₂ --O--CH₂ --(CH₂ OCH₂)_n --CH₂ --O--CH₂ CH₂ --OCH₃ ; and n=8-450; with the proviso that R¹ and R² are not both hydrogen, which is useful as an immunosuppressive, antiinflammatory, antifungal, antiproliferative, and antitumor agent.

Claims

1. A compound of the structure ##STR4## wherein R¹ and R² are each, independently, hydrogen or --COCH₂ --S--CH₂ CH₂ --O--CH₂ --(CH₂ OCH₂)_n --CH₂ --O--CH₂ CH₂ --OCH₃ ;

and n=8-450;

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

2. The compound of claim 1 wherein n=8-200.

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 31,42-diester with methoxypoly(ethylene glycol) thiol 5000.

7. The compound of claim 1 which is 42-ester with methoxypoly(ethylene glycol) thiol 5000.

8. The compound of claim 1 which is 42-ester with methoxypoly(ethylene glycol) thiol 750.

9. A pharmaceutical composition which comprises a compound of the structure ##STR5## wherein R¹ and R² are each, independently, hydrogen or --COCH₂ --S--CH₂ CH₂ --O--CH₂ --(CH₂ OCH₂)_n --CH₂ --O--CH₂ CH₂ --OCH₃ ;

and n=8-450;

with the proviso that R¹ and R² are not both hydrogen, and a pharmaceutical carrier.