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, and O;
Y is S or 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, C 1-5 alkyl, hydroxy, C 2-4 acyl, 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;
R 5 and R 6 are independently selected from halo, phenyl, C 1-9 alkyl, C 1-8 alkoxy, C 2-9 alkenyl, C 2-9 alkenyloxy, C 3-7 cycloalkyl, C 3-7 cycloalkoxy, C 3-7 cycloalkyl-C 1-7 alkyl, C 3-7 cycloalkyl-C 1-7 alkoxy, C 3-7 cycloalkyloxy-C 1-8 alkyl, and C 3-7 cycloalkyloxy-C 1-7 alkoxy, or
R 5 and R 6 together form C 1-9 alkylidenyl or C 3-9 alkenylidenyl; or R 5 ,
R 6 and the carbon atom to which they are attached together form C 3-7 cycloalkyl or 5- or 6-membered heterocyclyl;
n is 0, 1 or 2; and
m is 0, 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 Y is O.
5. The compound of claim 1 wherein Y is S.
6. The compound of claim 1 wherein m is 1.
7. The compound of claim 1 wherein m is 2.
8. The compound of claim 1 wherein n is 1.
9. The compound 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.
10. The compound of claim 9 wherein R 1 and R 2 are independently selected from H, methyl, methoxy, F and Cl.
11. The compound of claim 1 wherein R 3 and R 4 are independently selected from H, halo, cyano, acetyl, C 1-2 alkyl, and C 1-2 alkoxy.
12. The compound of claim 11 wherein R 3 is independently selected from H, F, Cl, hydroxy, methyl, and methoxy.
13. The compound of claim 11 wherein R 4 is independently selected from F, Cl, methyl, methoxy, trifluoromethyl, trifluoromethoxy, difluoromethyl, difluoromethoxy, fluoromethyl, fluoromethoxy, chlorodifluoromethyl, chlorodifluoromethoxy, dichlorofluoromethyl, and dichlorofluoromethoxy.
14. 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.
15. The compound of claim 1 wherein R 5 and R 6 together form C 1-9 alkylidenyl or C 3-9 alkenylidenyl, or R 5 , R 6 and the carbon atom to which they are attached together form C 3-7 cycloalkyl.
16. The compound of claim 1 wherein R 5 and R 6 are independently selected from halo, phenyl, C 1-9 alkyl, C 1-8 alkoxy, C 2-9 alkenyl, C 2-9 alkenyloxy, C 3-7 cycloalkyl, C 3-7 cycloalkoxy, C 3-7 cycloalkyl-C 1-7 alkyl, C 3-7 cycloalkyl-C 1-7 alkoxy, C 3-7 cycloalkyloxy-C 1-6 alkyl, and C 3-7 cycloalkyloxy-C 1-7 alkoxy.
17. 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, acetyl, methyl, methoxy, trifluoromethyl, trifluoromethoxy, difluoromethyl, difluoromethoxy, fluoromethyl, fluoromethoxy, chlorodifluoromethyl, chlorodifluoromethoxy, dichlorofluoromethyl, and dichlorofluoromethoxy.
18. The compound 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.
19. The compound of claim 1 wherein X is O and Y is O.
20. The compound of claim 1 wherein X is O and Y is S.
21. The compound of claim 1 wherein X is a covalent bond and Y is S.
22. The compound of claim 1 which is [2-methyl-4-[[2-[[[4-(trifluoromethyl)phenyl]thio]methyl]-2-propenyl]thio]phenoxy]-acetic acid.