O-alkylated rapamycin derivatives and their use, particularly as immunosuppressants

• US 5,665,772 A
• Filed: 04/07/1995
• Issued: 09/09/1997
• Est. Priority Date: 10/09/1992
• Status: Expired due to Term

• Current Assignee: Novartis Ag
• Original Assignee: Sandoz Inc. (Novartis Ag)
• Inventors: Sedrani, Richard, Cottens, Sylvain
• Primary Examiner(s): BOND, ROBERT
• Application Number:
  US08/416,673
• Time in Patent Office: 886 Days
• Field of Search: 540/456, 514/514
• US Class Current: 514/514
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• 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 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• 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: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 498/18 Bridged systems

Abstract

Novel derivatives of rapamycin, particularly 9-deoxorapamycins, 26-dihydro-rapamycins, and 40-0-substituted and 28,40-0,0-di-substituted rapamycins, are found to have pharmaceutical utility, particularly as an immunosuppressants.

Claims

1. A compound of the formula ##STR3## wherein R¹ is hydroxy(C_1-6)alkyl or hydroxy(C_1-3)alkoxy(C_1-3)alkyl.

2. A compound according to claim 1 in which R¹ is hydroxy(C_1-3)alkyl or hydroxy(C_1-3)alkoxy(C_1-3)alkyl.

3. A compound according to claim 1 in which R¹ is hydroxy(C_1-3)alkyl.

4. A compound according to claim 1 in which R¹ is hydroxy(C_1-3)alkoxy(C_1-3)alkyl.

5. The compound according to claim 1 which is 40-O-(3-hydroxypropyl)-rapamycin.

6. The compound according to claim 1 which is 40-O-[2-(2-hydroxyethoxy)ethyl]-rapamycin.

7. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 and a pharmaceutically acceptable carrier therefor.

8. A method of inducing an immunosuppressant effect in a subject in need of immunosuppression, which comprises administering to said subject an immunosuppressant effective amount of a compound according to claim 1.

9. A method of preventing allograft rejection in a subject in need of such treatment, which comprises administering to said subject a compound according to claim 1 in an amount effective to prevent allograph rejection.

10. The compound according to claim 1 which is 40-O-(3-hydroxyethyl)-rapamycin.