Cyclosporins for the treatment of immune disorders

Abstract

The present invention relates to methods of treating or preventing an inflammatory or immune disorder in a subject while eliminating or reducing the toxicity associated with the administration of cyclosporin A, comprising systemically administering to said subject a pharmaceutical composition comprising a therapeutically effective amount of at least one compound of Formula I or a pharmaceutically acceptable salt, ester or prodrug thereof, in combination with a pharmaceutically-acceptable carrier or excipient: 1 in Formula I, the Formula for residue A is: 2 where X is absent, —C1-C6 alkyl-, or —C3-C6 cycloalkyl-; Y is selected from the groups: —C(O)—O—R1 where R1 is hydrogen, C1-C6 alkyl optionally substituted with halogen, heterocyclics, aryl, C1-C6 alkoxy or C1-C6 alkylthio, halogen substituted C1-C6 alkoxy or halogen substituted C1-C6 alkylthio; —C(O)—S—R1 where R1 is hydrogen, C1-C6 alkyl optionally substituted with halogen, heterocyclics, aryl, C1-C6 alkoxy or C1-C6 alkylthio, halogen substituted C1-C6 alkoxy or halogen substituted C1-C6 alkylthio; —C(O)—OCH2—OC(O)R2 where R2 is C1-C6 alkyl optionally substituted with halogen, C1-C6 alkoxy, C1-C6 alkylthio, heterocyclics, or aryl; —C(S)—O—R1 where R1 is hydrogen, C1-C6 alkyl optionally substituted with halogen, heterocyclics, aryl, C1-C6 alkoxy or C1-C6 alkylthio, halogen substituted C1-C6 alkoxy or halogen substituted C1-C6 alkylthio; and —C(S)—S—R1 where R1 is hydrogen, C1-C6 alkyl optionally substituted with halogen, heterocyclics, aryl, C1-C6 alkoxy or C1-C6 alkylthio, halogen substituted C1-C6 alkoxy, halogen substituted C1-C6 alkylthio; B is -αAbu-, -Val-, -Thr- or -Nva-; and U is -(D)Ala-, -(D)Ser- or —[O-(2-hydroxyethyl)(D)Ser]-, or —[O-acyl(D)Ser]- or —[O-(2-acyloxyethyl)(D)Ser]-.

Dependencies are inferred from the claim text.