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. wherein n is 1 or 2; m is 0, 1, 2, 3, or 4; q is 0 or 1; t is 0 or 1; R 1 is 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; one of R 3 and R 4 is hydrogen or hydroxy and the other is hydrogen; or R 3 and R 4 together are ═O; R 5 is hydrogen or alkyl having one, two, three, four or five 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
n is 1 or 2;
m is 0, 1, 2, 3, or 4;
q is 0 or 1;
t is 0 or 1;
R 1 is 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;
one of R 3 and R 4 is hydrogen or hydroxy and the other is hydrogen; or R 3 and R 4 together are ═O;
R 5 is hydrogen or alkyl having one, two, three, four or five carbon atoms;
A is 2,6-dimethylphenyl;
or a pharmaceutically acceptable salt of the compound.
2. The compound or salt of claim 1 , wherein n is 1; q is 0; t is 0; R 2 is hydrogen; R 5 is hydrogen; and m is 0, 2 or 4.
3. The compound or salt of claim 2 , wherein the compound is selected from the group consisting of 4-(3-(2,6-Dimethylbenzyloxy)phenyl)-butan-1-ol, 4-(3-(2,6-Dimethylbenzyloxy)phenyl)-4-hydroxybutan-1-ol, and 1-(3-(2,6-Dimethylbenzyloxy)phenyl)-4-hydroxybutan-1-one.
4. A pharmaceutical composition, 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 0, 1, 2, 3, or 4;
q is 0 or 1;
t is 0 or 1;
R 1 is 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;
one of R 3 and R 4 is hydrogen or hydroxy and the other is hydrogen; or R 3 and R 4 together are ═O;
R 5 is hydrogen or alkyl having one, two, three, four or five carbon atoms;
A is 2,6-dimethylphenyl;
or a pharmaceutically acceptable salt of the compound.
5. The pharmaceutical composition of claim 4 , wherein n is 1; q is 0; t is 0; R 2 is hydrogen; R 5 is hydrogen; and m is 0, 2 or 4.
6. The pharmaceutical composition of claim 5 , wherein the compound is selected from the group consisting of 4-(3-(2,6-Dimethylbenzyloxy)phenyl)-butan-1-ol, 4-(3-(2,6-Dimethylbenzyloxy)phenyl)-4-hydroxybutan-1-ol, and 1-(3-(2,6-Dimethylbenzyloxy)phenyl)-4-hydroxybutan-1-one.
7. The pharmaceutical composition of claim 4 in oral dosage form.