4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs
View Patent ↗The invention features 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs, compositions containing them, and methods of using them as PPAR delta modulators to treat or inhibit the progression of, for example, dyslipidemia.
1. A compound of Formula (II):
wherein
X is selected from a covalent bond, S, or 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 is 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 2 is H;
R 3 and R 4 are independently selected from H, halo, cyano, hydroxy, C 2-4 acyl, 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 compound of claim 1 wherein X is S or O.
3. The compound of claim 2 wherein X is O.
4. The compound of claim 1 wherein X is a covalent bond.
5. The compound of claim 1 wherein Y is O.
6. The compound of claim 1 wherein Y is S.
7. The compound of claim 1 wherein Z is O.
8. The compound of claim 1 wherein Z is CH or CH 2 .
9. The compound of claim 1 wherein -----W----- represents —CH 2 — or —CH 2 —CH 2 —.
10. The compound of claim 9 wherein -----W----- represents —CH 2 —.
11. The compound of claim 1 wherein -----W----- represents —CH═, —CH 2 —CH═, or —CH═CH—.
12. The compound 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.
13. The compound of claim 1 wherein R 1 is selected from H, C 1-3 alkyl, C 1-3 alkoxy, F, Cl, and Br.
14. The compound of claim 13 wherein R 1 is selected from H, methyl, methoxy, F and Cl.
15. The compound of claim 1 wherein R 3 and R 4 are independently selected from H, halo, cyano, hydroxy, acetyl, C 1-4 alkyl, and C 1-3 alkoxy.
16. The compound of claim 15 wherein R 3 is independently selected from H, F, Cl, methyl, and methoxy.
17. The compound of claim 15 wherein R 4 is independently selected from F, Cl, methyl, methoxy, trifluoromethyl, fluoromethyl, difluoromethyl, chlorodifluoromethyl, dichlorofluoromethyl, fluoromethoxy, difluoromethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy and trifluoromethoxy.
18. The compound 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.
19. The compound 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.
20. The compound of claim 1 wherein R 1 is selected from H, CF 3 , methyl, Cl, and methoxy.
21. The compound of claim 20 wherein X is a covalent bond.
22. The compound of claim 21 wherein X is covalent bond, Y is S and Z is O.
23. The compound of claim 1 wherein X is O and Y is O.
24. The compound of claim 1 which is selected from acetic acid, {4-[(2R)-2-hydroxy-3-(4-trifluoromethyl-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}; and
acetic acid, {4-[(2S)-2-hydroxy-3-(4-trifluoromethyl-phenoxy)-propylsulfanyl]-2-methyl-phenoxy}.
25. A pharmaceutical composition comprising a compound of claim 1 .
26. A compound which is {4-[2-ethoxy-3-(4-trifluoromethyl-phenoxy)-propoxy]-2-methyl-phenoxy}-acetic acid.