D-SER!8-CYCLOSPORINE MODIFIED ON THE HYDROXYL GROUP HAVING A SWITCHABLE INHIBITING EFFECT ON PROTEIN PHOSPHATASE CALCINEURINE AND SPECIFIC MANIPULIPULATABILITY OBTAINED THEREWITH OF THE IMMUNOSUPPRESSIVE EFFECT WHILE MAINTAINING INHIBITION OF PEPTIDYL-PROLYL-CIS-TRANS-ISOMERASE (PPI) E.G. FOR THE TREATMENT OF AUTOIMMUNE D

摘要

The invention relates to novel cyclic peptides from the cyclosporine series, the ability thereof to inhibit protein phosphatase calcineurine and which can be switched in order to act immuno-suppresively. Unexpectedly, it was discovered that by modifying the hydroxyl group of [D-Ser]8-- cyclosporine by means of suitable activatable substituents, it was possible to switch off the immunosuppressive effect of said cyclosporine derivatives. Since therapeutically applied doses of cyclosporine A contain many undesirable side effects, the value of the invention lies in the fact that immunosuppressive activity of the inventive cyclosporine derivatives can be stopped. It is also possible to use the non-immunosuppressive cyclosporine derivative in a mixture with the parent substance or in an exclusively therapeutic manner. In the case of a therapeutic application of the inventive switchable cyclosporine derivatives, it is possible to influence the effect thereof during therapy.