S1P1 RECEPTOR AGONISTS AND USE THEREOF

1 . A compound of Formula (I):

wherein:

m is 0, 1, 2 or 3;

n is 0, 1, 2 or 3;

o is 0, 1, 2 or 3;

A is a phenyl, heterocyclyl, three to six membered cycloalkyl, or a five or six membered heteroaryl ring;

L is a saturated 3, 4, 5, 6 or 7-member ring containing 0, 1 or 2 atoms selected from N, O and S and optionally containing a double bond, the ring being substituted by 0, 1 or 2 groups selected from F, Cl, C 1-4 alkyl, C 1-4 haloalkyl, OH, —OC 1-4 alkyl, and —OC 1-4 haloalkyl;

is selected from,

R 1 is selected from F, Cl, C 1-4 alkyl, C 1-4 haloalkyl, OH, CN, —OC 1-4 alkyl, and —OC 1-4 haloalkyl;

R 2 is selected from F, Cl, C 1-4 alkyl, C 1-4 haloalkyl, OH, —OC 1-4 alkyl, and —OC 1-4 haloalkyl;

R 3 is selected from F, Cl, C 1-4 alkyl, C 1-4 haloalkyl, OH, —OC 1-4 alkyl, amino, and —OC 1-4 haloalkyl;

Z is:

(i) a cycloalkyl substituted with amino, monoalkylamino or dialkylamino group; a cycloalkylalkyl substituted with one or two carboxy groups; a monosubstituted amino, disubstituted amino, carboxyalkylamino, hydroxyalkyl, substituted hydroxyalkyl, hydroxyalkoxy, substituted hydroxyalkoxy, aminoalkyl, aminoalkoxy, carboxyalkyl, substituted carboxyalkyl, carboxyalkyloxy, substituted carboxyalkyloxy, carboxyalkylthio, substituted carboxyalkylthio, carboxyalkylsulfonyl, substituted carboxyalkylsulfonyl, carboxyalkoxyalkyl, substituted carboxyalkoxyalkyl, aminocarbonyl, acylamino, sulfonylamino, heterocycloamino, heterocycloaminoalkyl, heterocycloaminocarbonyl, heterocycloaminooxy, or heteroaralkyl group;

(ii) a group of formula (b):

where:

q is 0, 1 or 2;

R 4 is selected from H, C 1-3 haloalkyl, C 1-6 alkyl;

R 5 is selected from H, C 1-3 haloalkyl, C 1-4 alkyl; or

R 4 and R 5 together with the carbon atom to which they are attached form a 3, 4, 5, 6 or 7-member carbocyclic ring substituted by 0, 1 or 2 groups selected from F, Cl, C 1-4 alkyl, C 1-4 haloalkyl, OH, —OC 1-4 alkyl, and —OC 1-4 haloalkyl;

R 6 is a lone pair of electrons or O;

R 7 is H or C 1-6 alkyl;

R 8 is selected from H, F, Cl, C 1-4 alkyl, C 1-4 haloalkyl, OH, —OC 1-4 alkyl, and —OC 1-4 haloalkyl; or

R 7 and R 8 , when taken together, form a group that is selected from —(CR 10 R 10 )—, —(CR 10 R 10 )O—, (CR 10 R 10 )—, —(CR 10 R 10 )(CR 10 R 10 )—, and —(CR 10 R 10 ) 3 —;

R 9 is selected from H, F, C 1-3 haloalkyl, C 1-4 allyl, OH and OC 1-4 alkyl; or R 8 and R 9 together with the carbon atom to which they are attached from cycloalkyl; and

each R 10 is independently in each instance selected from H, F, Cl, C 1-4 alkyl, C 1-4 haloalkyl, OH, —OC 1-4 alkyl, and —OC 1-4 haloalkyl; or

(iii) when R 3 is on a carbon atom of the phenyl ring that is adjacent to the carbon of the phenyl ring that is bonded to Z, then R 3 and Z can combine to form —CH═CH—NR 11 , —(CH 2 ) 2 NR 11 —, —CH 2 NR 11 CH 2 —, —(CH 2 ) 2 NR 11 CH 2 —, —N═CR 11 —NH—, or —N═CH—NR 11 —, where R 11 is selected from hydrogen, hydroxyalkyl, aminoalkyl, carboxyalkyl, substituted hydroxyalkyl or substituted carboxyalkyl; or aminocarbonyl; or

a pharmaceutically acceptable thereof.

2 . The compound of claim 1 wherein

is

3 . The compound of claim 2 wherein L is a saturated 3, 4, 5, 6 or 7-member ring the ring being substituted by 0, 1 or 2 groups selected from F, Cl, C 1-4 alkyl, C 1-4 haloalkyl, OH, —OC 1-4 alkyl, and —OC 1-4 haloalkyl.

4 . The compound of claim 3 wherein A is phenyl.

5 . The compound of claim 3 wherein A is cycloalkyl.

6 . The compound of claim 3 wherein A is five or six membered heterocyclyl.

7 . The compound of claim 3 wherein A is five or six membered heteroaryl.

8 . The compound of claim 4 wherein Z is a group of formula (b).

9 . The compound of claim 4 wherein Z is 3-carboxyazetidin-1-ylmethyl.

10 . The compound of claim 4 wherein Z is carboxyalkylamino, hydroxyalkyl, substituted hydroxyalkyl, hydroxyalkoxy, substituted hydroxyalkoxy, aminoalkyl, aminoalkoxy, carboxyalkyl, substituted carboxyalkyl, carboxyalkyloxy, substituted carboxyalkyloxy, carboxyalkoxyalkyl, substituted carboxyalkoxyalkyl, aminocarbonyl, acylamino, sulfonylamino, heterocycloamino, heterocycloaminoalkyl, heterocycloaminocarbonyl, heterocycloaminooxy, or heteroaralkyl.

11 . The compound of claim 1 wherein n is 0.

12 . The compound of claim 9 wherein m is 0, o is 1 and R 3 is fluoro.

13 . A pharmaceutical composition a compound of claim 1 and a pharmaceutically acceptable excipient.

14 . A method for treating an S1P1 receptor mediated condition in a patient comprising administering to the patient a therapeutically effective amount of a compound of claim 1 wherein the condition is selected from the group consisting of acute or chronic resection of tissue grafts, systemic lupus erythematosus, multiple sclerosis, rheumatoid arthritis, inflammatory bowel diseases, atopic asthma, type I diabetes, acute respiratory distress syndrome, sepsis, ischemia-reperfusion injury, metastatic hepatocellular carcinoma, androgen-independent prostate cancer, multiple myeloma, bladder cancer, renal cancer, acute lymphoblastic leukemia, chronic lymphocytic leukemia, B-cell lymphoma, acute myeloid leukemia, mantle cell lymphoma, pancreatic cancer, breast cancer, Behcet's disease, glomerulonephritis, uveitis, psoriasis, myasthenia gravis, Hashimoto's thyroiditis, autoimmune hemolytic anemia, autoimmune thrombocytopenic purpura, hepatitis and Wegner's granuloma.

15 . The method of claim 14 wherein the disease is multiple sclerosis.

16 - 17 . (canceled)