METHODS OF TREATING AUTOIMMUNE AND INFLAMMATORY DISEASES AND DISORDERS

1 . A method of treating or managing an inflammatory or autoimmune disease or disorder, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of the formula:

or a pharmaceutically acceptable salt thereof, wherein:

A is an optionally substituted heterocycle;

R 1 is hydrogen or optionally substituted lower alkyl;

R 5 is OR 5A or OC(O)R 5A ;

R 6 is OR 6A or OC(O)R 6A ;

R 7 is OR 7A or OC(O)R 7A ;

R 8 is hydrogen, CH 2 OR 8A or CH 2 OC(O)R 8A ; and

each of R 5A , R 6A , R 7A and R 8A is independently hydrogen or lower alkyl.

2 . The method of claim 1 , wherein the compound is of the formula:

or a pharmaceutically acceptable salt thereof, wherein:

X is N or NR 9 ;

Y is CR 4 , N, NR 9 , O or S;

Z is CR 4 , CHR 4 , N, NR 9 , O or S;

R 1 , is hydrogen or optionally substituted lower alkyl;

each R 4 is independently OR 4A , OC(O)R 4A , hydrogen, halogen, or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heteroalkyl, heterocycle, alkylheterocycle, or heterocyclealkyl;

R 5 is OR 5A or OC(O)R 5A ;

R 6 is OR 6A or OC(O)R 6A ;

R 7 is OR 7A or OC(O)R 7A ;

R 8 is hydrogen, CH 2 OR 8A or CH 2 OC(O)R 8A ;

each R 9 is independently hydrogen or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heteroalkyl, heterocycle, alkylheterocycle, or heterocyclealkyl; and

each of R 4A , R 5A , R 6A , R 7A and R 8A is independently hydrogen or lower alkyl.

3 . The method of claim 2 , wherein X is N.

4 . The method of claim 2 , wherein Y is NR 4 .

5 . The method of claim 2 , wherein Y is O.

6 . The method of claim 2 , wherein Z is CHR 4 .

7 . The method of claim 2 , wherein R 4 is hydrogen.

8 . (canceled)

9 . (canceled)

10 . The method of claim 2 , wherein one or more of R 5 , R 6 , R 7 , and R 8 is hydroxyl or acetate.

11 . The method of claim 10 , wherein all of R 5 , R 6 , and R 7 are hydroxyl.

12 . (canceled)

13 . The method of claim 1 , wherein the compound is of the formula:

or a pharmaceutically acceptable salt thereof, wherein:

X is CR 4 , CHR 4 , N, NR 9 , O or S;

Y is CR 4 , CHR 4 , N, NR 9 , O or S;

Z is CR 4 , CHR 4 , N, NR 9 , O or S;

R 1 is hydrogen or optionally substituted lower alkyl; and

R 3 is optionally substituted alkyl;

each R 4 is independently OR 4A , OC(O)R 4A , hydrogen, halogen, or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heteroalkyl, heterocycle, alkylheterocycle, or heterocyclealkyl;

R 5 is OR 5A or OC(O)R 5A ;

R 6 is OR 6A or OC(O)R 6A ;

R 7 is OR 7A or OC(O)R 7A ;

R 8 is hydrogen, CH 2 OR 8A or CH 2 OC(O)R 8A ;

each R 9 is independently hydrogen or optionally substituted alkyl, aryl, alkylaryl, arylalkyl, heteroalkyl, heterocycle, alkylheterocycle, or heterocyclealkyl; and

each of R 4A , R 5A , R 6A , R 7A and R 8A is independently hydrogen or lower alkyl.

14 . The method of claim 13 , wherein X is N.

15 . The method of claim 13 , wherein Y is CHR 4 .

16 . The method of claim 13 , wherein Z is S.

17 . The method of claim 13 , wherein R 4 is hydrogen.

18 . The method of claim 13 , wherein R 4 is optionally substituted lower alkyl.

19 . The method of claim 13 , wherein one or more of R 5 , R 6 , R 7 , and R 8 is hydroxyl or acetate.

20 . The method of claim 19 , wherein all of R 5 , R 6 , and R 7 are hydroxyl.

21 . (canceled)

22 . (canceled)

23 . (canceled)

24 . (canceled)

25 . The method of claim 1 , wherein the compound is:

(1R,2S,3R)-1-(2-(5-methylisoxazol-3-yl)-1H-imidazol-5-yl)butane-1,2,3,4-tetraol;

(1R,2S,3R)-1-(2-(5-ethylisoxazol-3-yl)-1H-imidazol-5-yl)butane-1,2,3,4-tetraol;

(1R,2S,3R)-1-(2-(isoxazol-3-yl)-1H-imidazol-5-yl)butane-1,2,3,4-tetraol;

(1R,2S,3R)-1-(2-(2-methylthiazol-4-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol;

(1R,2S,3R)-1-(2-(1-benzyl-1H-1,2,4-triazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol hydrochloride;

(1R,2S,3R)-1-(1H,1′H-2,2′-biimidazol-5-yl)butane-1,2,3,4-tetraol;

(1R,2S,3R)-1-(2-(5-methoxy-4,5-dihydroisoxazol-3-yl)-1H-imidazol-5-yl)butane-1,2,3,4-tetraol; or

(1R,2S,3R)-1-(2-(5-methyl-1H-pyrazol-3-yl)-1H-imidazol-5-yl)butane-1,2,3,4-tetraol;

or a pharmaceutically acceptable salt thereof.

26 . The method of claim 25 , wherein the compound is (1R,2S,3R)-1-(2-(isoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol.

27 . The method of claim 1 , wherein the disease or disorder is ankylosing spondylitis, asthma, atopic dermatitis, Behcet's disease, graft-vs-host disease, Kawasaki syndrome, lupus erythematosus, multiple sclerosis, myasthenia gravis, pollinosis, psoriasis, psoriatic arthritis, rheumatoid arthritis, scleroderma, transplant rejection, type 1 diabetes, or uveitis.

28 . The method of claim 27 , wherein the disease or disorder is multiple sclerosis.

29 . The method of claim 27 , wherein the disease or disorder is rheumatoid arthritis.

30 . A method of treating or managing multiple sclerosis, comprising administering to a patient in need thereof a therapeutically effective amount of (1R,2S,3R)-1-(2-(isoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol.

31 . A method of treating or managing rheumatoid arthritis, comprising administering to a patient in need thereof a therapeutically effective amount of (1R,2S,3R)-1-(2-(isoxazol-3-yl)-1H-imidazol-4-yl)butane-1,2,3,4-tetraol.