Compound for the treatment of metabolic disorders
View Patent ↗Compounds useful for the treatment of various metabolic disorders, such as insulin resistance syndrome, diabetes, hyperlipidemia, fatty liver disease, cachexia, obesity, atherosclerosis and arteriosclerosis, are disclosed.
1. A compound of the formula:
wherein
n is 1 or 2;
q is 0 or 1;
t is 0 or 1;
R 5 is alkyl having from 1 to 3 carbon atoms;
m is 1;
X is —CH 2 — and R 1 is ethyl, and
A is phenyl, substituted by 1 or 2 groups selected from: fluoro, alkyl having 1 or 2 carbon atoms, perfluoromethyl, alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy; or
m is 0 or 1,
X is —CH 2 CH 2 — and R 1 is hydrogen or alkyl having from 1 to 7 carbon atoms, and
A is phenyl, substituted by 1 or 2 groups selected from: halo, alkyl having 1 or 2 carbon atoms, perfluoromethyl, alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy,
or when R 1 is hydrogen, a pharmaceutically acceptable salt of the compound; or
m is 0 or 1,
X is —CH 2 CH(NHAc)— and R 1 is hydrogen or alkyl having from 1 to 7 carbon atoms, and
A is phenyl, unsubstituted or substituted by 1 or 2 groups selected from: halo, alkyl having 1 or 2 carbon atoms, perfluoromethyl, alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy,
or when R 1 is hydrogen, a pharmaceutically acceptable salt of the compound.
2. The compound or salt of claim 1 , wherein R 1 is hydrogen or ethyl.
3. The compound or salt of claim 1 , wherein q is 0.
4. The compound or salt of claim 1 , wherein X is —CH 2 CH 2 —.
5. The compound or salt of claim 1 , wherein A is phenyl, unsubstituted or substituted by 1 or 2 groups selected from: halo, alkyl having 1 or 2 carbon atoms, perfluoromethyl, alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy;
wherein each halo is independently fluoro or chloro.
6. The compound or salt of claim 5 , wherein each halo substituent on phenyl ring A is fluoro.
7. The compound or salt of claim 6 , wherein phenyl ring A is substituted by 2 fluoro groups.
8. The compound or salt of claim 1 , wherein A is phenyl, unsubstituted or substituted by 1 or 2 groups selected from: halo, alkyl having 1 carbon atom, perfluoromethyl, alkoxy having 1 carbon atom, and perfluoromethoxy.
9. A compound having the formula:
wherein
n is 1 or 2;
m is 0 or 1;
q is 0 or 1;
t is 0 or 1;
R 5 is alkyl having from 1 to 3 carbon atoms; and
X is —CH 2 — and R 1 is ethyl, and
one of R 2 and R 3 is selected from fluoro, alkyl having 1 or 2 carbon atoms, perfluoromethyl, alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy, and the other is selected from hydrogen, halo, alkyl having 1 or 2 carbon atoms, perfluoromethyl, alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy; or
X is —CH 2 CH 2 — and R 1 is hydrogen or alkyl having from 1 to 7 carbon atoms, and
one of R 2 and R 3 is selected from hydrogen, halo, alkyl having 1 or 2 carbon atoms, perfluoromethyl, alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy, and the other is selected from halo, alkyl having 1 or 2 carbon atoms, perfluoromethyl, alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy,
or when R 1 is hydrogen, a pharmaceutically acceptable salt of the compound; or
X is —CH 2 CH(NHAc)— and R 1 is hydrogen or alkyl having from 1 to 7 carbon atoms, and
R 2 and R 3 are each independently selected from hydrogen, halo, alkyl having 1 or 2 carbon atoms, perfluoromethyl, alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy,
or when R 1 is hydrogen, a pharmaceutically acceptable salt of the compound.
10. The compound or salt of claim 9 , wherein R 1 is hydrogen or ethyl.
11. The compound or salt of claim 10 , wherein the compound is 4-[4-(2-(N-(2-fluorobenzyl)-N-methylamino)ethoxy)phenyl)]-4-oxobutyric acid.
12. The compound or salt of claim 10 , wherein the compound is (2RS)2-(N-acetyl)-4-(4-(2,6-difluorobenzyloxy)phenyl)-4-oxobutyric acid.
13. The compound or salt of claim 10 , wherein the compound is 4-(3-(4-trifluoromethylbenzyloxy)phenyl)-4-oxobutyric acid.
14. The compound of claim 9 , having the formula:
wherein
n is 1 or 2;
m is 0 or 1;
p is 1 and R 1 is ethyl, and
one of R 2 and R 3 is selected from fluoro, alkyl having 1 or 2 carbon atoms, perfluoromethyl, alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy, and the other is selected from hydrogen, halo, alkyl having 1 or 2 carbon atoms, perfluoromethyl, alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy; or
p is 2 and R 1 is hydrogen or alkyl having from 1 to 7 carbon atoms, and
one of R 2 and R 3 is selected from hydrogen, halo, alkyl having 1 or 2 carbon atoms, perfluoromethyl, alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy, and the other is selected from halo, alkyl having 1 or 2 carbon atoms, perfluoromethyl, alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy,
or when R 1 is hydrogen, a pharmaceutically acceptable salt of the compound.
15. The compound or salt of claim 14 , wherein R 1 is hydrogen or ethyl.
16. The compound or salt of claim 15 , wherein the compound is 4-(3-(2,6-Dimethoxybenzyloxy)phenyl)-4-oxobutyric acid.
17. The compound or salt of claim 14 , wherein one of R 2 and R 3 is hydrogen or halo and the other is halo.
18. The compound or salt of claim 17 , wherein the compound is 4-(4-(3-fluorobenzyloxy)phenyl)-4-oxobutyric acid.
19. The compound or salt of claim 17 , wherein the compound is 4-(4-(4-fluorobenzyloxy)phenyl)-4-oxobutyric acid.
20. The compound or salt of claim 17 , wherein the compound is 4-(4-(2-chlorobenzyloxy)phenyl)-4-oxobutyric acid.
21. The compound or salt of claim 17 , wherein R 2 is fluoro and R 3 is hydrogen.
22. The compound or salt of claim 21 , wherein the compound is 4-(4-(2-fluorobenzyloxy)phenyl)-4-oxobutyric acid.
23. The compound or salt of claim 21 , wherein the compound is 4-(4-(2-(2-fluorophenyl)ethoxy)phenyl)-4-oxobutyric acid.
24. The compound or salt of claim 21 , wherein the compound is ethyl 4-(4-(2-fluorobenzyloxyl)phenyl)-4-oxobutyrate.
25. The compound of claim 21 , ethyl 4-(3-(2-fluorobenzyloxyl)phenyl)-4-oxobutyrate.
26. The compound or salt of claim 15 , wherein R 2 is fluoro and R 3 is fluoro.
27. The compound or salt of claim 26 , wherein the compound is 4-(4-(2,5-difluorobenzyloxy)phenyl)-4-oxobutyric acid.
28. The compound or salt of claim 26 , wherein the compound is 4-(4-(2,4-difluorobenzyloxy)phenyl)-4-oxobutyric acid.
29. The compound of claim 26 , Ethyl 4-(4-(2,6-difluorobenzyloxy)phenyl)-3-oxobutyrate.
30. The compound or salt of claim 15 , wherein R 2 is methyl.
31. The compound or salt of claim 30 , wherein the compound is 4-(3-(2-Fluoro-6-methylbenzyloxy)phenyl)-4-oxobutyric acid.
32. The compound of claim 30 , Ethyl 4-(3-(2,6-dimethylbenzyloxyl)phenyl)-4-oxobutyrate.
33. The compound or salt of claim 30 , wherein the compound is 4-(4-(2,6-dimethylbenzyloxy)phenyl)-4-oxobutyric acid.
34. The compound of claim 26 , having the formula:
wherein
n is 1 or 2;
m is 0;
R 1 is H or alkyl having from 1 to 7 carbon atoms;
or when R 1 is hydrogen, a pharmaceutically acceptable salt of the compound.
35. The compound or salt of claim 34 , wherein the compound is 4-(4-(2,6-difluorobenzyloxy)phenyl)-4-oxobutyric acid.
36. The compound of claim 34 , Ethyl 4-(4-(2,6-difluorobenzyloxyl)phenyl)-4-oxobutyrate.
37. The compound or salt of claim 34 , wherein the compound is 4-(3-(2,6-difluorobenzyloxy)phenyl)-4-oxobutyric acid.
38. The compound or salt of claim 34 , wherein the compound is 4-(2-(2,6-difluorobenzyloxy)phenyl)-4-oxobutyric acid.