4-(phenoxyalkyl)thio)-phenoxyacetic acids and analogs

1. A method for treating or inhibiting the progression of a PPAR-delta mediated condition, said method comprising administering to a patient in need of treatment a pharmaceutically effective amount of a compound of Formula (II):

wherein

X is O;

Y is S or O;

- - - - - W - - - - - represents a group selected from —CH═, —CH 2 —, —CH 2 —CH 2 —, —CH 2 —CH═, and —CH═CH—;

Z is selected from O, CH, and CH 2 , provided when Y is O, Z is O;

R 1 and R 2 are independently selected from H, C 1-3 alkyl, C 1-3 alkoxy, halo, and NR a R b wherein R a and R b are independently H or C 1-3 alkyl;

R 3 and R 4 are independently selected from H, halo, cyano, hydroxy, acetyl, C 1-5 alkyl, C 1-4 alkoxy, and NR c R d wherein R c and R d are independently H or C 1-3 alkyl, provided that R 3 and R 4 are not both H;

n is 1 or 2;

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the PPAR-delta mediated condition is selected from the group consisting of diabetes, cardiovascular diseases, Metabolic X Syndrome, hypercholesterolemia, hypo-HDL-cholesterolemia, hyper-LDL-cholesterolemia, dyslipidemia, atherosclerosis, and obesity.

3. The method of claim 1 wherein Y is O.

4. The method of claim 1 wherein Y is S.

5. The method of claim 1 wherein Z is O.

6. The method of claim 1 wherein Z is CH or CH 2 .

7. The method of claim 1 wherein - - - W - - - represents —CH 2 — or —CH 2 —CH 2 —.

8. The method of claim 1 wherein - - - - - W - - - - - represents —CH═, —CH 2 —CH═, or —CH═CH—.

9. The method of claim 1 wherein R 3 and R 4 are independently selected from H, halo, cyano, C 1-4 alkyl, and C 1-3 alkoxy.

10. The method of claim 1 wherein R 1 and R 2 are independently selected from H, C 1-3 alkyl, C 1-3 alkoxy, F, Cl, and Br.

11. The method of claim 1 wherein R 3 and R 4 are independently selected from H, halo, cyano, hydroxy, C 2-4 acyl, C 1-4 alkyl, and C 1-3 alkoxy.

12. The method of claim 1 wherein R 3 is selected from methyl, methoxy, H, Cl, Br, I, OH, —CH(CF 3 ) 2 , CF 3 , —OCF 3 , —N(CH 3 ) 2 , —O—CH 2 COOH, and —COCH 3 , and R 4 is selected from H, Cl, and methyl.

13. The method of claim 1 wherein R 3 is selected from H, F, Cl, methyl, and methoxy, and R 4 is selected from F, Cl, methyl, fluoromethyl, difluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethyl, trifluoromethoxy, and methoxy.

14. The method of claim 1 wherein R 1 is selected from H, CF 3 , methyl, Cl, and methoxy, and R 2 is selected from H, Cl, and methyl.

15. The method of claim 1 wherein Y is O and Z is O.

16. The method of claim 1 wherein Y is S and Z is O.

17. The method of claim 1 wherein

R 1 is selected from H, CF 3 , methyl, Cl, and methoxy;

R 2 is selected from H, Cl, and methyl;

R 3 is selected from H, F, Cl, methyl, and methoxy; and

R 4 is selected from F, Cl, methyl, trifluoromethyl, trifluoromethoxy, fluoromethyl, fluoromethoxy, difluoromethyl, difluoromethoxy, and methoxy.

18. The method of claim l wherein

Y is O;

R 3 is selected from H, F, Cl, methyl, and methoxy; and

R 4 is selected from F, Cl, methyl, CF 3 , OCF 3 and methoxy.