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

A method for treating or preventing graft versus host disease or for treating an autoimmune disease selected from the group consisting of arthritis, rheumatic diseases, autoimmune hematological disorders, systemic lupus erythematosus, polychondritis, sclerodoma, Wegener granulamatosis, dermatomyositis, chronic active hepatitis, myasthenia gravis, psoriasis, Steven-Johnson syndrome, idiopathic sprue, autoimmune inflammatory bowel disease, endocrine ophthalmopathy, Grave's disease, sarcoidosis, multiple sclerosis, primary billiary cirrhosis, juvenile diabetes, anterior uveitis, posterior uveitis, keratoconjunctivitis sicca, vernal keratoconjunctivitis, interstitial lung fibrosis, psoriatic arthritis, glomerulonephritis (with and without nephrotic syndrome), and juvenile dermatomyostis comprising administering to a person in need thereof an effective amount of 40-O-(2-hydroxyethyl)-rapamycin.

A method for treating or preventing the rejection of a transplanted organ or graft versus host disease or for treating an autoimmune disease selected from the group consisting of arthritis, rheumatic diseases, autoimmune hematological disorders, systemic lupus erythematosus, polychondritis, sclerodoma, Wegener granulamatosis, dermatomyositis, chronic active hepatitis, myasthenia gravis, psoriasis, Steven-Johnson syndrome, idiopathic sprue, autoimmune inflammatory bowel disease, endocrine ophthalmopathy, Grave's disease, sarcoidosis, multiple sclerosis, primary billiary cirrhosis, juvenile diabetes, anterior uveitis, posterior uveitis, keratoconjunctivitis sicca, vernal keratoconjunctivitis, interstitial lung fibrosis, psoriatic arthritis, glomerulonephritis (with and without nephrotic syndrome), and juvenile dermatomyostis comprising administering to a host in need thereof an effective amount of a first compound of the formula

• wherein R1 is hydroxy(C1-6)alkyl or hydroxy(C1-3)alkoxy(C1-3)alkyl
• and a second compound which is Ciclosporin, FK-506, an immunosuppressive derivative of Ciclosporin or FK-506, a corticosteroid, azathioprene, an immunosuppressive monoclonal antibody, an antiviral, or an antibiotic.

A pharmaceutical composition comprising a therapeutically effective amount of a compound of the formula

• wherein R1 is hydroxy(C1-3)alkyl
• and a pharmaceutically acceptable carrier therefor.

A pharmaceutical composition comprising a therapeutically effective amount of 40-O-(2-hydroxyethyl)-rapamycin and a pharmaceutically acceptable carrier therefor.

A pharmaceutical composition comprising a therapeutically effective amount of a first compound which is of the formula

• wherein R1 is hydroxy(C1-6)alkyl or hydroxy(C1-3)alkoxy(C1-3)alkyl
• and a second compound which is Ciclosporin, FK-506, an immunosuppressive derivative of Ciclosporin or FK-506, a corticosteroid, azathioprene, an immunosuppressive monoclonal antibody, an antiviral, or an antibiotic, and a pharmaceutically acceptable carrier therefor.