Compounds for the treatment of metabolic disorders
View Patent ↗Agents useful for the treatment of various metabolic disorders, such as insulin resistance syndrome, diabetes, polycystic ovary syndrome, hyperlipidemia, fatty liver disease, cachexia, obesity, atherosclerosis and arteriosclerosis are disclosed. The agent is a compound of Formula (I): wherein m is 0, 1, 2, 3, 4, 5, 6, 7 or 8; R 1 is hydrogen or alkyl having from 1 to 3 carbon atoms; and R 2 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 1 or 2 groups selected from: halo, hydroxy, alkyl having 1 or 2 carbon atoms, perfluoromethyl, alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy; 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; 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 compound of formula I by a ring carbon; Alternatively, the agent can be a pharmaceutically acceptable salt of the compound of Formula (I).
1. A compound of the formula:
wherein
m is 0, 1, 2, 3, 4, 5, 6, 7 or 8;
R 1 is hydrogen or alkyl having from 1 to 3 carbon atoms;
R 2 is hydrogen, halo, alkyl having from 1 to 3 carbon atoms, or alkoxy having from 1 to 3 carbon atoms;
A is phenyl, independently substituted at each of the 2-position and the 6-position by a substituent selected from the group consisting of: chloro, bromo, iodo, hydroxy, alkyl having 1 or 2 carbon atoms, perfluoromethyl; alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy;
or a pharmaceutically acceptable salt of the compound.
2. The compound or salt of claim 1 , wherein m is 2 or 4; R 2 is hydrogen; and
A is phenyl, independently substituted at each of the 2-position and the 6-position by a substituent selected from the group consisting of: chloro, bromo, iodo, hydroxy, alkyl having 1 or 2 carbon atoms, and perfluoromethyl.
3. The compound or salt of claim 2 , wherein A is 2,6-dimethylphenyl.
4. The compound or salt of claim 1 wherein the compound is 4-(3-(2,6-Dimethylbenzoyloxy)phenyl)-4-oxobutanoic acid.
5. 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
m is 0, 1, 2, 3, 4, 5, 6, 7 or 8;
R 1 is hydrogen or alkyl having from 1 to 3 carbon atoms;
R 2 is hydrogen, halo, alkyl having from 1 to 3 carbon atoms, or alkoxy having from 1 to 3 carbon atoms;
A is phenyl, independently substituted at each of the 2-position and the 6-position by a substituent selected from the group consisting of: chloro, bromo, iodo, hydroxy, alkyl having 1 or 2 carbon atoms, perfluoromethyl; alkoxy having 1 or 2 carbon atoms, and perfluoromethoxy;
or a pharmaceutically acceptable salt of the compound.
6. The pharmaceutical composition of claim 5 , wherein m is 2 or 4; R 2 is hydrogen; and
A is phenyl, independently substituted at each of the 2-position and the 6-position by a substituent selected from the group consisting of: chloro, bromo, iodo, hydroxy, alkyl having 1 or 2 carbon atoms, and perfluoromethyl.
7. The pharmaceutical composition of claim 6 , wherein A is 2,6-dimethylphenyl.
8. The pharmaceutical composition of claim 7 wherein the compound is 4-(3-(2,6-Dimethylbenzoyloxy)phenyl)-4-oxobutanoic acid.
9. The pharmaceutical composition of claim 5 in oral unit dosage form.
10. The pharmaceutical composition of claim 5 for use in the treatment of a condition selected from the group consisting of insulin resistance syndrome, diabetes, polycystic ovary syndrome, hyperlipidemia, fatty liver disease, cachexia, obesity, atherosclerosis, arteriosclerosis.
11. The compound or salt of claim 1 , wherein A is phenyl, independently substituted at each of the 2-position and the 6-position by a substituent selected from the group consisting of: chloro, bromo, iodo, hydroxy, alkyl having 1 or 2 carbon atoms, and perfluoromethyl.
12. The pharmaceutical composition of claim 5 , wherein A is phenyl, independently substituted at each of the 2-position and the 6-position by a substituent selected from the group consisting of: chloro, bromo, iodo, hydroxy, alkyl having 1 or 2 carbon atoms, and perfluoromethyl.