Compositions for binding sphingosine-1-phosphate receptor 1 (S1P1), imaging of S1P1, and methods of use thereof

1. A compound having a structure of Formula (I) or (II), or a pharmaceutically acceptable salt thereof:

wherein

R 1 is halo-substituted C 1 -C 6 alkoxy;

R 2 is C 1 -C 4 haloalkyl or cyano;

R 3 , R 9 and R 10 are each independently hydrogen, halo, hydroxy, amino, C 1 -C 6 alkyl, C 1 -C 6 alkoxy,

 wherein at least one of R 3 , R 9 and R 10 is not hydrogen;

R 4 is hydrogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, or halo-substituted C 1 -C 6 alkoxy; and

R 5 , R 6 , R 7 and R 8 are each independently hydrogen, halo, hydroxy, C 1 -C 6 alkyl, or C 1 -C 6 alkoxy, and wherein R 3 is not —CH 2 OH when R 1 is —OCH 2 CH 2 F and R 2 is —CF 3 .

2. The compound of claim 1 wherein R 1 is —OCH 2 CH 2 F.

3. The compound of claim 1 wherein R 4 is hydrogen.

4. The compound of claim 1 wherein R 2 is —CF 3 .

5. The compound of claim 1 wherein at least one of R 3 , R 9 or R 10 is C 1 -C 6 alkyl or C 1 -C 6 alkoxy.

6. The compound of claim 1 wherein R 9 and R 10 are each hydrogen.

7. The compound of claim 1 wherein R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 are each hydrogen.

8. The compound of claim 1 wherein R 3 is

or —CH(OH)CH 2 OH.

9. The compound of claim 1 wherein R 9 and R 10 are each independently hydrogen, halo, hydroxy, C 1 -C 6 alkyl, or C 1 -C 6 alkoxy.

10. The compound of claim 1 having a structure selected from the group consisting of:

pharmaceutically acceptable salts thereof, and mixtures thereof.

11. The compound of claim 1 wherein the compound comprises an atom that is a synthetic radioactive isotope.

12. The compound of claim 11 wherein the synthetic radioactive isotope is selected from the group consisting of 11 C, 13 N, 15 O, 18 F, 76 Br, 123 I, and 125 I.

13. The compound of claim 11 having a structure selected from the group consisting of:

pharmaceutically acceptable salts thereof, and mixtures thereof.

14. A pharmaceutical composition comprising at least one compound of claim 13 and at least one pharmaceutically acceptable excipient.

15. A pharmaceutical composition comprising at least one compound of claim 11 and at least one pharmaceutically acceptable excipient.

16. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound of claim 11 wherein the composition comprises from about 0.001 mg to about 10 g of the compound.

17. A method of diagnosing or monitoring an S1P1 associated disease, disorder or condition in a mammal comprising administering a composition comprising a compound of claim 11 to the mammal; and detecting the compound in the mammal, wherein the S1P1 associated disease disorder or condition is selected from the group consisting of an inflammatory disease, a neuroinflammatory disease, an autoimmune disease, a pulmonary infection disease, a vascular injury disease, a neurological disease, a psychological disorder, a cardiovascular disease, atherosclerosis, multiple sclerosis, rheumatoid arthritis, and cancer.

18. The method of claim 17 wherein the S1P1 associated disease, disorder or condition is multiple sclerosis.

19. A method of quantifying S1P1 expression in a mammalian brain or central nervous system comprising administering a composition comprising a compound of claim 11 to the mammal; and detecting the compound in the mammal.

20. A method of diagnosing or monitoring an S1P1 associated disease, disorder or condition in a mammal comprising administering a composition of comprising a compound of claim 13 to the mammal; and detecting the compound in the mammal, wherein the S1P1 associated disease disorder or condition is selected from the group consisting of an inflammatory disease, a neuroinflammatory disease, an autoimmune disease, a pulmonary infection disease, a vascular injury disease, a neurological disease, a psychological disorder, a cardiovascular disease, atherosclerosis, multiple sclerosis, rheumatoid arthritis, and cancer.