Cyclosporins for the treatment of immune disorders

1. A method of treating an inflammatory or immune disorder in a subject while 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:

wherein A is:

X is absent, —C 1 –C 6 alkyl-, or —C 3 –C 6 cycloalkyl

Y is selected from the group consisting of:

(i) C(O)—O—R 1 , where R 1 is hydrogen, C 1 –C 6 alkyl, optionally substituted with halogen, heterocyclic, aryl, C 1 –C 6 -alkoxy, C 1 –C 6 alkylthio, halogen-substituted C 1 –C 6 alkoxy, or halogen-substituted C 1 –C 6 alkylthio;

(ii) C(O)—S—R 1 , where R 1 is as previously defined;

(iii) C(O)—OCH 2 —OC(O)R 2 , where R 2 is C 1 –C 6 alkyl, optionally substituted with halogen, C 1 –C 6 alkoxy, C 1 –C 6 alkylthio, heterocyclic or aryl;

(iv) C(S)—O—R 1 , where R 1 is as previously defined, and

(v) C(S)—S—R 1 , where R 1 is as previously defined;

B is -αAbu-, -Val-, -Thr- or -Nva-; and

U is -(D)Ala-, -(D)Ser-, —[O-(2-hydroxyethyl)(D)Ser]-, —[O-acyl(D)Ser]- or —[O-(2-acyloxyethyl)(D)Ser]-.

2. The method of claim 1 , wherein said inflammatory or immune disorder is organ transplant rejection.

3. The method of claim 1 , wherein said inflammatory or immune disorder is selected from the group consisting of: rheumatoid arthritis, inflammatory bowel disease, psoriasis, atopic dermatitis, asthma, allergic rhinitis, and chronic obstructive pulmonary disease.

4. The method of claim 1 , wherein said systemically administering is accomplished orally, intraperitoneally, intravenously, intramuscularly, intrasternally, subcutaneously, or through intravenous injection or infusion.