Cyclosporins

1. A compound of Formula (I):

wherein A is an amino acid of Formula (II):

wherein:

R 0 is H or CH 3 ;

X=hydrogen;

hydroxyl; or

hydroxyl group derivatized with an alkanoyl, aryloyl, alkylaminocarbonyl, arylaminocarbonyl, arylalkylaminocarbonyl, alkyloxycarbonyl, aryloxycarbonyl, or arylalkyloxycarbonyl group;

CO— in Formula II is covalently bound to an α-amino group of B in Formula I to form an amide linkage, and —N—R 0 in Formula II is covalently bound to a carboxylic acid of K to form an amide linkage;

B is an amino acid selected from the group consisting of:

α-aminobutyric acid;

alanine;

threonine;

valine;

norvaline; and

a modified α-aminobutyric acid, alanine, valine, or norvaline, wherein a carbon atom in a side chain is substituted with a hydroxyl group;

C is a sarcosine;

D is an amino acid selected from the group consisting of:

leucine;

N-methyl leucine;

valine;

γ-hydroxy-N-methyl leucine; and

γ-hydroxy leucine;

E is an amino acid selected from the group consisting of:

valine;

norvaline; and

a modified valine or norvaline, wherein a carbon atom in a side chain is substituted with a hydroxyl group;

F is an amino acid selected from the group consisting of:

leucine;

N-methyl leucine;

γ-hydroxy-N-methyl leucine; and

γ-hydroxy leucine;

G is α-aminobutyric acid or alanine;

H is D-alanine;

I and J are independently selected from the group consisting of:

leucine;

N-methyl leucine;

γ-hydroxy-N-methyl leucine; and

γ-hydroxy leucine;

K is N-methyl valine or valine;

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 , wherein the compound has the following formula:

3. A compound according to claim 1 , wherein the compound has the following formula:

4. A compound according to claim 1 , wherein the compound has the following formula:

5. A compound according to claim 1 , wherein the compound has the following formula:

6. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 and one or more pharmaceutical excipients.

7. A method of treating a mammal with a chronic inflammatory disease comprising:

administering a therapeutically effective amount of the compound of claim 1 to the mammal under conditions effective to treat the chronic inflammatory disease.

8. The method of claim 7 , wherein the chronic inflammatory disease is selected from the group consisting of asthma, rheumatoid arthritis, multiple sclerosis, psoriasis, and ulcerative colitis.