Bicyclic aryl sphingosine 1-phosphate analogs

1. A method for treatment of a pathological condition or symptom in a mammal, wherein the activity of sphingosine 1-phosphate receptors is implicated and agonism of such activity is desired, comprising administering to said mammal an effective amount of a compound of formula (I):

wherein:

X 1 is hydrogen, halo, hydroxy, nitro, cyano, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, acyl, aminoacyl, —NR f R g , —N(R f )SO 2 R g , —SO 2 R f , —SO 2 NR f R g , —CO 2 R f , trialkylamino, aryl, or heteroaryl;

X 2 is hydrogen, halo, hydroxy, nitro, cyano, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, acyl, aminoacyl, —NR f R g , —N(R f )SO 2 R g , —SO 2 R f , —SO 2 NR f R g , —CO 2 R f , trialkylamino, aryl, or heteroaryl;

X 3 is hydrogen, halo, hydroxy, nitro, cyano, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, acyl, aminoacyl, —NR f R g , —N(R f )SO 2 R g , —SO 2 R f , —SO 2 NR f R g , —CO 2 R f , trialkylamino, aryl, or heteroaryl;

X 4 is hydrogen, halo, hydroxy, nitro, cyano, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, acyl, aminoacyl, —NR f R g , —N(R f )SO 2 R g , —SO 2 R f , —SO 2 NR f R g , —CO 2 R f , trialkylamino, aryl, or heteroaryl;

X 5 is hydrogen, halo, hydroxy, nitro, cyano, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, acyl, aminoacyl, —NR f R g , —N(R f )SO 2 R g , —SO 2 R f , —SO 2 NR f R g , —CO 2 R f , trialkylamino, aryl, or heteroaryl;

X 6 is hydrogen, halo, hydroxy, nitro, cyano, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, acyl, aminoacyl, —NR f R g , —N(R f )SO 2 R g , —SO 2 R f , —SO 2 NR f R g , —CO 2 R f , trialkylamino, aryl, or heteroaryl;

Y is —OR f , —(CR f R g )OR f , —(CR f R g ) 2 OR f , —O—P(O)(OR f )OR g , —OC(O)R c , —C(O)OR c , —(CR f R g )—P(O)(OR f )OR g , —(C(OH)R f )—P(O)(OR f )OR g , —S—P(O)(OR f )OR g , tetrazole, —SO 2 NHR f , —SO 3 , —CONHR f , —Si(OH) 2 , or —B(OH) 2 ;

W is —CR f R g —, —NR f —, —O—, —S—, —SO—, or —SO 2 —;

Cy has the formula:

wherein

Z 1 is a bond, —[C(R d R e )] x —, —CR d ═CR e —, —O—, —NR f —;

Z 2 is a bond, —[C(R d R e )] y —, —CR d ═CR e —, —O—, —NR f —;

Z 3 is a bond, —[C(R d R e )] z —, —CR d ═CR e —, —O—, —NR f —;

each of x, y, and z, independently, is 1 to 3;

each R d , independently, is H, halo, hydroxy, alkyl, haloalkyl, alkenyl, alkoxy, cycloalkyl, —C(O)NR f R g , —NR f R g , —NR f C(O)R g , or —SO 2 NR f R g ;

each R e , independently, is H, halo, hydroxy, alkyl, haloalkyl, alkenyl, alkoxy, or cycloalkyl, —C(O)NR f R g , —NR f R g , —NR f C(O)R g , or —SO 2 NR f R g ;

R 1a and R 1b , independently, are hydrogen, halo, hydroxy, nitro, cyano, —NR f R g , alkyl, haloalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, alkoxy, cycloalkylalkoxy, cycloalkenylalkoxy, heterocyclylalkoxy, arylalkoxy, heteroarylalkoxy, acyl, cycloalkylacyl, cycloalkenylacyl, heterocyclylacyl, arylacyl, heteroarylacyl, thioalkyl, alkenyl, alkynyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl;

or R 1a and R 1b , when taken together, are C 2 -C 5 alkylene optionally terminated by or interrupted by 1 or 2 oxygen atoms, or C 2 -C 5 alkenylene optionally terminated by or interrupted by 1 or 2 oxygen atoms;

R 2a and R 2b , independently, are hydrogen, halo, hydroxy, nitro, cyano, —NR f R g , alkyl, haloalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, alkoxy, cycloalkylalkoxy, cycloalkenylalkoxy, heterocyclylalkoxy, arylalkoxy, heteroarylalkoxy, acyl, cycloalkylacyl, cycloalkenylacyl, heterocyclylacyl, arylacyl, heteroarylacyl, thioalkyl, alkenyl, alkynyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl;

or R 1a and R 2a , when taken together, are C 1 -C 5 alkylene optionally terminated by or interrupted by 1 or 2 oxygen atoms, or C 2 -C 5 alkenylene optionally terminated by or interrupted by 1 or 2 oxygen atoms;

wherein R 1a , R 1b , R 2a , and R 2b are each, independently, substituted with 0-5 substituents selected from halo, hydroxy, nitro, cyano, —NR f R g , or —CO 2 R f ;

L 1 is —CH 2 —, —CHF—, or —CF 2 —;

Z 4 is hydrogen, halo, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, or —OR f ;

or Z 4 is —CH 2 — bound to the carbon atom to which Y is bound;

or L 1 , Z 4 , Y, and the atoms to which they are bound form a 4-7 membered cycloalkyl group or a 4-7 membered heterocyclyl group having 1 or 2 heteroatoms selected from O and N;

R a is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl; wherein each of alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocycle are optionally substituted with 1 to 5 substituents independently selected from the group consisting of halo, oxo, —CN, —CHO, —CF 3 , —OH, —NO 2 , alkyl, —OCF 3 , alkoxy, cycloalkoxy, cycloalkenoxy, amino, alkylamino, dialkylamino, acylamino, aminoacyl, alkylsulfonyl, alkylaminosulfonyl, and dialkylaminosulfonyl;

R b is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl; wherein each of alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocycle are optionally substituted with 1 to 5 substituents independently selected from the group consisting of halo, oxo, —CN, —CHO, —CF 3 , —OH, —NO 2 , alkyl, —OCF 3 , alkoxy, cycloalkoxy, cycloalkenoxy, amino, alkylamino, dialkylamino, acylamino, aminoacyl, alkylsulfonyl, alkylaminosulfonyl, and dialkylaminosulfonyl;

or R b and Z 4 are taken to together to form —C(O)O— or ═C(R f )O—;

R c is alkyl, aryl, trifluoromethyl, methylsulfonyl, trifluoromethylsulfonyl, p-tolylsulfonyl, or a group selected such that —OCOR c is a leaving group;

each R f , independently, is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl; wherein each of alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocycle are optionally substituted with 1 to 5 substituents independently selected from the group consisting of halo, oxo, —CN, —CHO, —CF 3 , —OH, —NO 2 , alkyl, —OCF 3 , alkoxy, cycloalkoxy, cycloalkenoxy, amino, alkylamino, dialkylamino, acylamino, aminoacyl, alkylsulfonyl, alkylaminosulfonyl, and dialkylaminosulfonyl;

each R g , independently, is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl; wherein each of alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocycle are optionally substituted with 1 to 5 substituents independently selected from the group consisting of halo, oxo, —CN, —CHO, —CF 3 , —OH, —NO 2 , alkyl, —OCF 3 , alkoxy, cycloalkoxy, cycloalkenoxy, amino, alkylamino, dialkylamino, acylamino, aminoacyl, alkylsulfonyl, alkylaminosulfonyl, and dialkylaminosulfonyl;

or a pharmaceutically acceptable salt or prodrug thereof.

2. The method of claim 1 , wherein the pathological condition is neuropathic pain.

3. The method of claim 1 , wherein the pathological condition is an autoimmune disease.

4. The method of claim 3 , further comprising administering to said mammal an effective amount of a drug selected from the group consisting of: a corticosteroid, a bronchodilator, an antiasthmatic, an antiinflammatory, an antirheumatic, an immunosuppressant, an antimetabolite, an immunomodulator, an antipsoriatic, and an antidiabetic.

5. The method of claim 3 , wherein the autoimmune disease is uveitis, type I diabetes, rheumatoid arthritis, inflammatory bowel diseases, lupus, asthma, psoriasis, or multiple sclerosis.

6. The method of claim 4 , wherein the autoimmune disease is multiple sclerosis.

7. The method of claim 1 , wherein the prevention or treatment of the pathological condition is altering lymphocyte trafficking.

8. The method of claim 7 , wherein altering lymphocyte trafficking provides prolonged allograft survival.

9. The method of claim 8 , wherein the allograft is for transplantation.

10. The method of claim 1 , wherein W is —O—.

11. The method of claim 1 , wherein R a and R b , independently, are each H or alkyl.

12. The method of claim 1 , wherein Y is —OR f .

13. The method of claim 1 , wherein Y is —OH or —O—P(O)(OR f )OR g .

14. The method of claim 13 , wherein X 6 is H, halo, alkyl, cycloalkyl, or haloalkyl.

15. The method of claim 1 , wherein R 1a and R 2a are both hydrogen.

16. The method of claim 1 , wherein Z 1 is —CH 2 CH 2 —.

17. The method of claim 16 , wherein Z 2 is —CH 2 —.

18. The method of claim 17 , wherein Z 3 is a bond.

19. The method of claim 15 , wherein R 1b is fluoro, chloro, bromo, iodo, methyl, difluoromethyl, trifluoromethyl, ethyl, 1,1-difluoroethyl, propyl, isopropyl, n-butyl, i-butyl, t-butyl, n-pentyl, isopentyl, 1,1-dimethylpropyl, neopentyl, cyclopentyl, n-hexyl, cyclohexyl, methoxy, trifluoromethoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, t-butoxy, n-pentyloxy, i-pentyloxy, 1,1-dimethylpropoxy, neopentyloxy, cyclopentyloxy, n-hexyloxy, or cyclohexyloxy.

20. A method for treatment of a pathological condition or symptom in a mammal, wherein the activity of sphingosine 1-phosphate receptors is implicated and agonism of such activity is desired, comprising administering to said mammal an effective amount of a compound of formula (II):

wherein

X 1 is hydrogen, halo, hydroxy, nitro, cyano, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, acyl, aminoacyl, —NR f R g , —N(R f )SO 2 R g , —SO 2 R f , —SO 2 NR f R g , —CO 2 R f , trialkylamino, aryl, or heteroaryl;

X 2 is hydrogen, halo, hydroxy, nitro, cyano, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, acyl, aminoacyl, —NR f R g , —N(R f )SO 2 R g , —SO 2 R f , —SO 2 NR f R g , —CO 2 R f , trialkylamino, aryl, or heteroaryl;

X 3 is hydrogen, halo, hydroxy, nitro, cyano, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, acyl, aminoacyl, —NR f R g , —N(R f )SO 2 R g , —SO 2 R f , —SO 2 NR f R g , —CO 2 R f , trialkylamino, aryl, or heteroaryl;

X 4 is hydrogen, halo, hydroxy, nitro, cyano, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, acyl, aminoacyl, —NR f R g , —N(R f )SO 2 R g , —SO 2 R f , —SO 2 NR f R g , —CO 2 R f , trialkylamino, aryl, or heteroaryl;

X 5 is hydrogen, halo, hydroxy, nitro, cyano, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, acyl, aminoacyl, —NR f R g , —N(R f )SO 2 R g , —SO 2 R f , —SO 2 NR f R g , —CO 2 R f , trialkylamino, aryl, or heteroaryl;

X 6 is hydrogen, halo, hydroxy, nitro, cyano, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, acyl, aminoacyl, —NR f R g , —N(R f )SO 2 R g , —SO 2 R f , —SO 2 NR f R g , —CO 2 R f , trialkylamino, aryl, or heteroaryl;

Y is —OR f , —(CR f R g )OR f , —(CR f R g ) 2 OR f , —O—P(O)(OR f )OR g , —OC(O)R c , —C(O)OR c , —(CR f R g )—P(O)(OR f )OR g , —(C(OH)R f )—P(O)(OR f )OR g , —S—P(O)(OR f )OR g , tetrazole, —SO 2 NHR f , —SO 3 , —CONHR f , —Si(OH) 2 , or —B(OH) 2 ;

W is —CR f R g —, —NR f —, —O—, —S—, —SO—, or —SO 2 —;

Z 4 is hydrogen, halo, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, or —OR f ;

or Z 4 is —CH 2 — bound to the carbon atom to which Y is bound;

or Z 4 , Y, and the atoms to which they are bound form a 4-7 membered cycloalkyl group or a 4-7 membered heterocyclyl group having 1 or 2 heteroatoms selected from O and N;

R c is alkyl, aryl, trifluoromethyl, methylsulfonyl, trifluoromethylsulfonyl, p-tolylsulfonyl, or a group selected such that —OCOR c is a leaving group;

each R f , independently, is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl; wherein each of alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocycle are optionally substituted with 1 to 5 substituents independently selected from the group consisting of halo, oxo, —CN, —CHO, —CF 3 , —OH, —NO 2 , alkyl, —OCF 3 , alkoxy, cycloalkoxy, cycloalkenoxy, amino, alkylamino, dialkylamino, acylamino, aminoacyl, alkylsulfonyl, alkylaminosulfonyl, and dialkylaminosulfonyl;

each R g , independently, is hydrogen, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl; wherein each of alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocycle are optionally substituted with 1 to 5 substituents independently selected from the group consisting of halo, oxo, —CN, —CHO, —CF 3 , —OH, —NO 2 , alkyl, —OCF 3 , alkoxy, cycloalkoxy, cycloalkenoxy, amino, alkylamino, dialkylamino, acylamino, aminoacyl, alkylsulfonyl, alkylaminosulfonyl, and dialkylaminosulfonyl;

R 1a is hydrogen, halo, hydroxy, nitro, cyano, —NR f R g , alkyl, haloalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, alkoxy, cycloalkylalkoxy, cycloalkenylalkoxy, heterocyclylalkoxy, arylalkoxy, heteroarylalkoxy, acyl, cycloalkylacyl, cycloalkenylacyl, heterocyclylacyl, arylacyl, heteroarylacyl, thioalkyl, alkenyl, alkynyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl;

Z 1 is a bond, —[C(R d R e )] x —, or —CR d ═CR e —;

Z 2 is a bond, —[C(R d R e )] y —, or —CR d ═CR e —;

each of x and y independently, is 1 to 3;

each R d , independently, is hydrogen, halo, hydroxy, alkyl, alkenyl, alkoxy, or cycloalkyl;

each R e , independently, is hydrogen, halo, hydroxy, alkyl, alkenyl, alkoxy, or cycloalkyl;

or a pharmaceutically acceptable salt or prodrug thereof.

21. The method of claim 20 , wherein Y is —OR f .

22. The method of claim 21 , wherein Y is —OH or —O—P(O)(OR f )OR g .

23. The method of claim 22 , wherein X 6 is H, halo, alkyl, cycloalkyl, or haloalkyl.

24. The method of claim 23 , wherein Z 1 is —CH 2 CH 2 —.

25. The method of claim 24 , wherein Z 2 is —CH 2 CH 2 —.

26. The method of claim 25 , wherein R 1a is hydrogen, halo, hydroxy, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, arylalkyl, alkoxy, cycloalkylalkoxy, arylalkoxy, or aryl.

27. The compound of claim 20 , wherein Y is —OH or —OP(O)(OH) 2 ; Z 4 is H or —OH; X 1 , X 2 , X 3 , X 4 , and X 5 are each H; and X 6 is H, halo, alkyl, cycloalkyl, or haloalkyl.

28. The method of claim 20 , wherein Z 1 is —(CH 2 ) x — and Z 2 is —(CH 2 ) y —.

29. The method of claim 28 , wherein R 1a is alkyl, haloalkyl, cycloalkyl, aryl, or arylalkoxy.

30. The method of claim 20 , wherein the compound has the formula:

31. A method for treatment of a pathological condition or symptom in a mammal, wherein the activity of sphingosine 1-phosphate receptors is implicated and agonism of such activity is desired, comprising administering to said mammal an effective amount of a compound selected from the group consisting of: (R)-2-amino-2-(6-(cis-4-butylcyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(4-butylcyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-butylcyclohexyloxy)naphthalen-2-yl)propan-1-ol; 2-amino-2-(6-(cis-4-butylcyclohexyloxy)naphthalen-2-yl)propane-1,3-diol; (R)-2-amino-2-(6-(cis-4-butylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(cis-4-butylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)propan-1-phosphoric acid; (R)-2-amino-2-(6-(cis-4-butylcyclohexyloxy)naphthalen-2-yl)propyl dihydrogen phosphate; (R)-2-amino-2-(6-(trans-4-butylcyclohexyloxy)naphthalen-2-yl)propyl dihydrogen phosphate; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)propyl dihydrogen phosphate; (R)-2-amino-2-(6-(cis-4-(4-(pentan-3-yloxy)phenyl)cyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(cis-4-(4-isopropoxyphenyl)cyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(cis-4-(4-methoxyphenyl)cyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(cis-4-phenylcyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(cis-4-phenylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-{6-[trans-4-(1,1-dimethyl-propyl)-cyclohexyloxy]-5-trifluoromethyl-naphthalen-2-yl}-propan-1-ol; (R)-2-amino-2-(6-(4-pentylcyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(4-propylcyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(cis-4-methylcyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(cis-4-ethylcyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(4-(trifluoromethyl)cyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(4,4-dimethylcyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)propan-1-ol; 2-amino-2-[6-(cis-4-butylcyclohexyloxy)-5-trifluoromethyl-naphthalen-2-yl]-propane-1,3-diol; 2-amino-2-[6-(cis-4-butylcyclohexyloxy)-5-iodo-naphthalen-2-yl]-propane-1,3-diol; 2-amino-2-[6-(trans-4-tert-butylcyclohexyloxy)-5-trifluoromethyl-naphthalen-2-yl]-propane-1,3-diol; 2-amino-2-[6-(trans-4-tert-butyl-cyclohexyloxy)-naphthalen-2-yl]-propane-1,3-diol; 2-amino-2-[6-(trans-4-tert-butyl-cyclohexyloxy)-5-iodo-naphthalen-2-yl]-propane-1,3-diol; 2-amino-2-(6-trans-[3-(benzyloxymethyl)cyclobutoxy)]naphthalen-2-yl)propane-1,3-diol; 2-amino-2-(6-cis-[3-(benzyloxymethyl)cyclobutoxy)]naphthalen-2-yl)propane-1,3-diol; 2-amino-2-[6-(3-trans-benzyloxymethylcyclobutoxy)-5-(trifluoromethyl)naphthalen-2-yl)]propane-1,3-diol; 2-amino-2-[6-(3-cis-benzyloxymethylcyclobutoxy)-5-(trifluoromethyl)naphthalen-2-yl)]propane-1,3-diol; (R)-2-amino-2-[6-(3-trans-benzyloxymethylcyclobutoxy)naphthalen-2-yl)]propan-1-ol; (R)-2-amino-2-[6-(3-cis-benzyloxymethylcyclobutoxy)naphthalen-2-yl)]propan-1-ol; (R)-2-amino-2-[6-(4-trans-tert-pentylcyclohexyloxy)naphthalen-2-yl]propan-1-ol; (R)-2-amino-2-[6-(4-cis-tert-pentylcyclohexyloxy)naphthalen-2-yl]propan-1-ol; (R)-2-amino-2-[6-(3-cis-benzyloxymethylcyclobutoxy)-5-trifluoromethylnaphthalen-2-yl)]propan-1-ol; 2-amino-2-[6-(3-cis-(benzyloxymethylcyclobutoxy)naphthalen-2-yl]-3-hydroxypropyl dihydrogen phosphate; (R)-2-amino-2-{6-[trans-4-(1,1-dimethyl-propyl)-cyclohexyloxy]naphthalen-2-yl}-propan-1-ol; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)-5-methoxynaphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-butyl-cyclohexyloxy)-5-trifluoromethylnaphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-butyl-cyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-trifluoromethylcyclohexyloxy)-5-fluoronaphthalen-2-yl)propan-1-ol; (R)-2-Amino-2-[6-(decahydro-naphthalen-2-yloxy)-naphthalen-2-yl]-propan-1-ol; (R)-2-Amino-2-[6-(bicyclohexyl-4-yloxy)-naphthalen-2-yl]-propan-1-ol; (R)-2-Amino-2-[6-(4-isopropyl-cyclohexyloxy)-naphthalen-2-yl]-propan-1-ol; (R)-2-Amino-2-[6-(4-cyclopentyl-cyclohexyloxy)-naphthalen-2-yl]-propan-1-ol; (R)-2-Amino-2-[6-(4-sec-butyl-cyclohexyloxy)-naphthalen-2-yl]-propan-1-ol; (R)-2-Amino-2-[6-(cis-4-cyclopentyl-cyclohexyloxy)-5-trifluoromethyl-naphthalen-2-yl]-propan-1-ol; (R)-2-Amino-2-[6-(trans-4-cyclopentyl-cyclohexyloxy)-5-trifluoromethyl-naphthalen-2-yl]-propan-1-ol; Phosphoric acid mono-{(R)-2-amino-2-[6-(4-cyclopentyl-cyclohexyloxy)-5-trifluoromethyl-naphthalen-2-yl]-propyl}ester; 2-Amino-2-[5-trifluoromethyl-6-(4-trifluoromethyl-cyclohexyloxy)-naphthalen-2-yl]-propane-1,3-diol; (R)-2-[6-(4-tert-butyl-cyclohexyloxy)-naphthalen-2-yl]-2-methylamino-propan-1-ol; phosphoric acid mono-{(R)-2-amino-2-{6-[4-(1,1-dimethylpropyl)-cyclohexyloxy)-5-trifluoromethyl-naphthalen-2-yl]-propyl}Ester; phosphoric acid mono-{(R)-2-amino-2-[6-(4-tert-butyl-cyclohexyloxy)-5-trifluoromethyl-naphthalen-2-yl]-propyl}Ester; (S)-2-amino-2-[6-(4-trans-tert-butyl-cyclohexyloxy)-5-trifluoromethyl-naphthalen-2-yl]-propan-1-ol; (S)-4-[6-(4-cis-tert-butyl-cyclohexyloxy)-naphthalen-2-yl]-4-methyl-oxazolidin-2-one; (S)-4-[6-(4-cis-tert-butyl-cyclohexyloxy)-5-trifluoromethyl-naphthalen-2-yl]-4-methyl-oxazolidin-2-one; (S)-2-amino-2-[6-(4-cis-tert-butyl-cyclohexyloxy)-5-trifluoromethyl-naphthalen-2-yl]-propan-1-ol; (R)-4-(6-hydroxy-5-(trifluoromethyl)naphthalen-2-yl)-4-methyloxazolidin-2-one; (R)-4-(6-(trans-4-tert-butylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)-4-methyloxazolidin-2-one; (R)-2-amino-2-(6-((4-tert-butylcyclohexyl)methyl)naphthalen-2-yl)propan-1-ol; 3-(6-(trans-4-tert-Butylcyclohexyloxy)naphthalen-2-yl)oxetan-3-amine; 3-(6-(trans-4-tert-butylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)oxetan-3-amine; (R)-2-Amino-2-(6-(cis-4-cyclohexylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)propan-1-ol; (R)-2-Amino-2-(6-(trans-4-cyclohexylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-cyclohexylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)propyl dihydrogen phosphate; (R)-2-Amino-2-(6-(cis-4-isopropylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)propan-1-ol; (R)-2-Amino-2-(6-(trans-4-isopropylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)propan-1-ol; (R)-2-Amino-2-(6-(trans-4-(1,1-difluoroethyl)cyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)propyl dihydrogen phosphate; 4 amino-4-(6-(trans-4-tert-butylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)pentanoic acid; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)-5-cyclopropylnaphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)-5-methylnaphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)-5-vinylnaphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)-5-(4-(trifluoromethoxy)phenyl)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)-5-(4-(methylsulfonyl)phenyl)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)-5-(pyrimidin-5-yl)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)-5-(4-ethoxyphenyl)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)-5-phenylnaphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)-5-(3-chlorophenyl)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)-5-(4-chlorophenyl)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)-5-chloronaphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(5-bromo-6-(trans-4-tert-butylcyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)-5,7,8-trichloronaphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-tert-butylcyclohexyloxy)-5-fluoronaphthalen-2-yl)propan-1-ol; 2-amino-2-(6-trans-4-tert-butylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)-3-hydroxypropyl dihydrogen phosphate Enantiomer 1; 2-amino-2-(6-trans-4-tert-butylcyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)-3-hydroxypropyl dihydrogen phosphate Enantiomer 2; (R)-4-Methyl-4-[6-(4-trifluoromethyl-cyclohexyloxy)-naphthalen-2-yl]-oxazolidin-2-one; (R)-4-Methyl-4-[6-(cis-4-trifluoromethyl-cyclohexyloxy)-naphthalen-2-yl]-oxazolidin-2-one; (R)-4-Methyl-4-[6-(trans-4-trifluoromethyl-cyclohexyloxy)-naphthalen-2-yl]-oxazolidin-2-one; (R)-2-Amino-2-[6-(cis-4-trifluoromethyl-cyclohexyloxy)-naphthalen-2-yl]-propan-1-ol; (R)-2-Amino-2-[6-(trans-4-trifluoromethyl-cyclohexyloxy)-naphthalen-2-yl]-propan-1-ol; Phosphoric acid mono-{(R)-2-amino-2-[6-(trans-4-trifluoromethyl-cyclohexyloxy)-naphthalen-2-yl]-propyl}Ester; (R)-2-Amino-2-[5-trifluoromethyl-6-(trans-4-trifluoromethyl-cyclohexyloxy)-naphthalen-2-yl]-propan-1-ol; Phosphoric acid mono-{(R)-2-amino-2-[5-trifluoromethyl-6-(trans-4-trifluoromethyl-cyclohexyloxy)-naphthalen-2-yl]-propyl}Ester; (R)-2-Amino-2-[6-(4-pentyl-cyclohexyloxy)-naphthalen-2-yl]-propan-1-ol; (R)-2-Amino-2-[6-(cis-4-pentyl-cyclohexyloxy)-naphthalen-2-yl]-propan-1-ol; (R)-2-Amino-2-[6-(trans-4-pentyl-cyclohexyloxy)-naphthalen-2-yl]-propan-1-ol; 2-[6-(trans-4-tert-Butyl-cyclohexyloxy)-5-trifluoromethyl-naphthalen-2-yl]-propan-1-ol; 2-Amino-2-[6-(trans-4-tert-butyl-cyclohexyloxy)-5-trifluoromethyl-naphthalen-2-yl]-propan-1-ol; 4-Amino-4-[6-(trans-4-trifluoromethyl-cyclohexyloxy)-naphthalen-2-yl]-pentanoic acid; 4-Amino-4-[6-(cis-4-trifluoromethyl-cyclohexyloxy)-naphthalen-2-yl]-pentanoic acid; 4-Amino-4-[5-trifluoromethyl-6-(trans-4-trifluoromethyl-cyclohexyloxy)-naphthalen-2-yl]-pentanoic acid; 4-Amino-4-[5-trifluoromethyl-6-(cis-4-trifluoromethyl-cyclohexyloxy)-naphthalen-2-yl]-pentanoic acid; (R)-2-amino-2-(6-(trans-4-(1,1-difluoroethyl)cyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-(1,1-difluoropropyl)cyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-(1,1-difluorobutyl)cyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(cis-4-(1,1-difluoroethyl)cyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(cis-4-(1,1-difluoropropyl)cyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(cis-4-(1,1-difluorobutyl)cyclohexyloxy)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-(1,1-difluoroethyl)cyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(trans-4-(1,1-difluoropropyl)cyclohexyloxy)-5-(trifluoromethyl)naphthalen-2-yl)propan-1-ol; (R)-2-amino-2-(6-(cis-4-tert-butylcyclohexyloxy)naphthalen-2-yl)propan-1-ol;

or a pharmaceutically acceptable salt or prodrug thereof.