Compounds for the treatment of metabolic disorders
View Patent ↗Agents useful for the treatment of various metabolic disorders, such as insulin resistance syndrome, diabetes, hyperlipidemia, fatty liver disease, cachexia, obesity, artherosclerosis and arteriosclerosis are disclosed. Formula (I) wherein n is 1 or 2; m is 0, 1, 2, 4 or 5; q is 0 or 1; t is 0 or 1; R 2 is alkyl from 1 to 3 carbon atoms; R 3 is hydrogen, halo, alkyl having from 1 to 3 carbon atoms, or alkoxy having from 1 to 3 carbon atoms; A is phenyl, unsubstituted or substituted by or 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 cycloaldyl having from 3 to 6 ring carbon atoms wherein the cycloaldyl is unsubstitited or one or two ring carbons are independently mono-substituted by methyl or ethyl; or a 5 or 6 membered heteroaromatic ring having 1 or 2 ring heteroatoms selected from N, S and O and the heteroaromatic ring is covalently bound to the remainder of the compounds of formula (I) by a ring carbon; and R 1 is hydrogen or alkyl having 1 or 2 carbon atoms. Alternatively, when R 1 is hydrogen, the biologically active agent can be a pharmaceutically acceptable salt of the compound of Formula (I).
1. A pharmaceutical composition adapted for oral administration, comprising a pharmaceutically acceptable carrier and from one milligram to four hundred milligrams of a biologically active agent,
wherein the agent is a compound of the formula:
wherein
n is 1 or 2;
m is 1, 2, 4, or 5;
q is 0 or 1;
t is 0 or 1;
R 2 is alkyl having from 1 to 3 carbon atoms;
R 3 is hydrogen, halo, alkyl having from 1 to 3 carbon atoms, or alkoxy having from 1 to 3 carbon atoms;
A is 2,6-dimethylphenyl; or 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
R 1 is hydrogen or alkyl having 1 or 2 carbon atoms;
or when R 1 is hydrogen, a pharmaceutically acceptable salt of the compound.
2. The pharmaceutical composition of claim 1 , wherein n is 1; q is 0; t is 0; R 3 is hydrogen; and A is 2,6-dimethylphenyl.
3. The pharmaceutical composition of claim 1 in oral dosage form.
4. The pharmaceutical composition of claim 2 , wherein the biologically active agent is selected from the group consisting of:
3-(2,6-Dimethylbenzyloxy)phenylacetic acid;
6-[3-(2,6-Dimethylbenzyloxy)-phenyl]-hexanoic acid;
Ethyl 6-[3-(2,6-dimethylbenzyloxy)-phenyl]-hexanoate;
5-[3-(2,6-Dimethylbenzyloxy)-phenyl]-pentanoic acid;
Ethyl 5-[3-(2,6-dimethylbenzyloxy)-phenyl]-pentanoate;
3-[3-(2,6-dimethylbenzyloxy)phenyl]-propionic acid; and
Ethyl 3-[3-(2,6-dimethylbenzyloxy)phenyl]-propanoate.
5. The pharmaceutical composition of claim 4 , wherein the biologically active agent is 3-(2,6-Dimethylbenzyloxy)-phenylacetic acid.
6. A biologically active agent, wherein the agent is a compound of the formula:
wherein
n is 1 or 2;
m is 1, 2, 4, or 5;
q is 0 or 1;
t is 0 or 1;
R 2 is alkyl having from 1 to 3 carbon atoms;
R 3 is hydrogen, halo, alkyl having from 1 to 3 carbon atoms, or alkoxy having from 1 to 3 carbon atoms;
A is 2,6-dimethylphenyl; and
R 1 is hydrogen or alkyl having 1 or 2 carbon atoms;
or when R 1 is hydrogen, a pharmaceutically acceptable salt of the compound, wherein the agent is substantially pure.
7. The biologically active agent of claim 6 , selected from the group consisting of:
3-(2.6-Dimethylbenzyloxy)phenylacetic acid;
6-[3-(2,6-Dimethylbenzyloxy)-phenyl]-hexanoic acid;
Ethyl 6-[3-(2,6-dimethylbenzyloxy)-phenyl]-hexanoate;
5-[3-(2,6-Dimethylbenzyloxy)-phenyl]-pentanoic acid;
Ethyl 5-[3-(2,6-dimethylbenzyloxy)-phenyl]-pentanoate;
3-[3-(2,6-dimethylbenzyloxy)phenyl]-propionic acid; and
Ethyl 3-[3-(2,6-dimethylbenzyloxy)phenyl]-propanoate.
8. The biologically active agent of claim 7 , being 3-(2,6-Dimethylbenzyloxy)-phenylacetic acid.