Vinyl phosphonate lysophosphatidic acid receptor antagonists

1. A compound having the formula

wherein Z is —CY═CH— in the trans (e) configuration;

Y is hydrogen or halogen,

each R 1 is independently halo, (C 1 -C 6 )alkyl, halo(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, —NH 2 , —NH(C 1 -C 6 )alkyl, —N((C 1 -C 6 )alkyl) 2 , or cyano; and

R 2 is hydrogen, halo, (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkoxyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, —NH 2 , —NH(C 1 -C 12 )alkyl, —N((C 1 -C 12 )alkyl) 2 , aryl, (C 1 -C 12 )alkaryl, aryl(C 1 -C 12 )alkyl, or aryl-substituted aryl(C 1 -C 12 )alkyl;

each R 3 is independently halo, (C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkyl, halo(C 1 -C 12 )alkoxyl, (C 3 -C 10 )cycloalkyl, (C 2 -C 12 )alkenyl, (C 2 -C 12 )alkynyl, —NH2, —NH(C 1 -C 12 ) alkyl, —N((C 1 -C 12 )alkyl) 2 , aryl, (C 1 -C 12 )alkaryl, aryl(C 1 -C 12 )alkyl, or aryl-substituted aryl(C 1 -C 12 )alkyl;

R 4 is (C 6 -C 24 )alkyl, halo(C 6 -C 24 )alkyl, (C 6 -C 24 )alkoxy, —NH2, —NH(C 1 -C 24 )alkyl, —N((C 1 -C 24 )alkyl) 2 , cyano, (C 3 -C 10 )cycloalkyl, (C 4 -C 15 )bicycloalkyl, (C 6 -C 24 )alkenyl, (C 6 -C 24 )alkenyl, (C 6 -C 24 )-alkynyl, aryl, (C 6 -C 24 )alkaryl, aryl(C 6 -C 24 )alkyl, or aryl-substituted aryl(C 6 -C 24 )alkyl;

wherein the alkyl, alkenyl aryl groups of R4 can be optionally substituted with halo, alkoxy or cyano; or

R 5 and R 6 are independently hydroxy, (C 1 -C 12 )alkyl-O—, (C 2 -C 12 )alkenyl-O—, (C 2 -C 12 )alkynyl-O—, (C 6 -C 10 )aryl-O—,

m is 0, 1, 2, 3, or 4; n is 0, 1, 2, or 3; or a pharmaceutically acceptable salt or ester thereof.

2. The compound of claim 1 , wherein R 2 is hydrogen, methyl, ethyl, fluoro, chloro, trifluoromethyl, trifluoromethoxy, 1,1,1-trifluoroethyl, 1,1,1-trifluoroethoxy, methoxy, ethoxy, propoxy, butoxy, pentoxy.

3. The compound of claim 1 , wherein Y is hydrogen, fluorine, chlorine or bromine.

4. The compound of claim 3 , wherein Y is hydrogen or fluorine.

5. The compound of claim 1 , wherein R 1 is fluorine, trifluoromethyl, trifluoromethoxy, 1,1,1-trifluoroethyl, 1,1,1-trifluoroethoxy, methoxy, or ethoxy.

6. The compound of claim 1 , wherein R 3 is fluorine, chlorine, bromine, trifluoro-methyl, methoxy, (C 1 -C 6 )alkyl, (C 1 -C 6 )haloalkyl, or (C 1 -C 6 )alkyl substituted with, alkoxy or cyano.

7. The compound of claim 6 , wherein R 3 is fluorine, trifluoromethyl, trifluoromethoxy, 1,1,1-trifluoroethyl, 1,1,1-trifluoroethoxy, methoxy, or ethoxy.

8. The compound of claim 1 , wherein R 2 is hydrogen, trifluoromethyl, trifluoromethoxy, 1,1,1-trifluoroethyl, or 1,1,1-trifluoroethoxy.

9. The compound of claim 8 , wherein R 2 is hydrogen, trifluoromethoxy, or 1,1,1-trifluoroethoxy.

10. The compound of claim 1 , wherein R 4 is alkyl, or alkenyl.

11. The compound of claim 10 , wherein R 4 is C 5 H 11 , C 6 H 13 , C 7 H 14 CH═CHC 8 H 17 or C 15 H 31 .

12. The compound of claim 11 , wherein R 4 is C 7 H 14 CH═CHC 8 H 17 and C 15 H 31 .

13. The compound of claim 1 , wherein R 5 and R 6 are independently hydroxy, methoxy, or ethoxy,

14. The compound of claim 13 , wherein R 5 and R 6 are independently hydroxy, methoxy, or ethoxy.

15. The compound of claim 1 , wherein having the formula:

16. A composition comprising the compound of claim 1 , and a pharmaceutically acceptable carrier.

17. A kit for administering at least one compound of claim 1 , to a patient in need thereof, said kit comprising a pharmaceutical composition comprising at least one compound, an applicator, and instructional material for the use thereof.