Compounds 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;
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
R 9 is hydrogen; and
X is —CH 2 CR 12 R 13 — wherein one of R 12 and R 13 is hydrogen or ethyl and the other is methyl, Q is OR 1 and R 1 is hydrogen or alkyl having from 1 to 7 carbon atoms; or X is —CH 2 CH 2 — and Q is NR 10 R 11 wherein one of R 10 and R 11 is hydrogen, alkyl having from 1 to 3 carbon atoms or hydroxy, and the other is hydrogen or alkyl having from 1 to 3 carbon atoms; or
R 9 is halo, or alkoxy having from 1 to 3 carbon atoms; and
X is —CH 2 —, Q is —OR 1 and R 1 is ethyl; or X is —CH 2 CR 12 R 13 — or —CH 2 CH(NHAc)— wherein each of R 12 and R 13 is independently hydrogen or methyl, Q is OR 1 and R 1 is hydrogen or alkyl having from 1 to 7 carbon atoms; or X is —CH 2 CH 2 — and Q is NR 10 R 11 wherein one of R 10 and R 11 is hydrogen, alkyl having from 1 to 3 carbon atoms or hydroxy, and the other is hydrogen or alkyl having from 1 to 3 carbon atoms; and
A is cycloalkyl having from 3 to 6 ring carbon atoms wherein the cycloalkyl is unsubstituted or one or two ring carbons are independently mono-substituted by methyl or ethyl;
or when R 1 is hydrogen, a pharmaceutically acceptable salt of the compound.
2. A compound of 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;
A is cycloalkyl having from 3 to 6 ring carbon atoms wherein the cycloalkyl is unsubstituted or one or two ring carbons are independently mono-substituted by methyl or ethyl; and
X is —CH 2 — and R 1 is ethyl; or X is —CH 2 CH 2 — or —CH 2 CH(NHAc)— and R 1 is hydrogen or alkyl having from 1 to 7 carbon atoms;
or when R 1 is hydrogen, a pharmaceutically acceptable salt of the compound.
3. The compound or salt of claim 2 , wherein R 1 is hydrogen or ethyl.
4. The compound or salt of claim 2 , wherein q is 0.
5. The compound or salt of claim 2 , wherein X is —CH 2 CH 2 —.
6. The compound or salt of claim 2 , wherein the cycloalkyl is unsubstituted or one or both ring carbons adjacent to the ring carbon covalently bound to the remainder of the compound of formula I are independently mono-substituted by methyl or ethyl.
7. The compound or salt of claim 6 , wherein A is unsubstituted cyclopropyl.
8. The compound or salt of claim 2 , wherein q is 1 and R 5 is methyl.
9. The compound or salt of claim 2 , wherein the compound is 4-(3-((Cyclobutyl)-methoxy)phenyl)-4-oxobutyric acid.
10. The compound of claim 2 , represented by the formula:
wherein
R 1 is hydrogen or alkyl having from 1 to 7 carbon atoms,
or when R 1 is hydrogen, a pharmaceutically acceptable salt of the compound.
11. The compound or salt of claim 10 , wherein R 1 is hydrogen or ethyl.
12. The compound or salt of claim 11 , wherein the compound is 4-(4-((cyclopropyl)-methyoxy)phenyl)-4-oxobutyric acid.
13. The compound or salt of claim 11 , wherein the compound is 4-(3-((cyclopropyl)-methoxy)phenyl)-4-oxobutyric acid.