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. wherein n is 1 or 2; m is 0, 1, 2, 3, 4 or 5; 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; R 3 is hydrogen or —(CH 2 ) g OH wherein g is 0, 1 or 2; R 4 is hydrogen, methyl or ethyl; 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 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; or a pharmaceutically acceptable salt of the compound.
1. A compound of the formula:
wherein
n is 1 or 2;
m is 1, 2, 3, 4 or 5;
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, or alkyl having from 1 to 3 carbon atoms;
R 3 is hydrogen or —(CH 2 ) g OH wherein g is 0, 1 or 2;
R 4 is hydrogen, methyl or ethyl;
A is 2,6-dimethylphenyl;
or a pharmaceutically acceptable salt of the compound.
2. The compound or salt of claim 1 , wherein the compound is represented by the formula
wherein A, R 1 , R 2 , R 3 , R 4 , t, q, n, and m have the values set forth in claim 1 .
3. The compound or salt of claim 2 , wherein m is 1; n is 1; q is 0; t is 0; R 2 is hydrogen; and R 4 is hydrogen.
4. The compound or salt of claim 3 , wherein the compound is N-Hydroxy-2-[3-(2,6-dimethylbenzyloxy)phenyl]acetamide.
5. The compound or salt of claim 3 , wherein the compound is 2-[3-(2,6-Dimethylbenzyloxy)phenyl]acetamide.
6. The compound or salt of claim 3 , wherein the compound is N-(2-Hydroxyethyl)-2-[3-(2,6-dimethylbenzyloxy)phenyl]acetamide.
7. A method for treating a mammalian subject with a condition selected from the group consisting of insulin resistance syndrome and diabetes, comprising administering to the subject an amount of a compound of the formula:
wherein
n is 1 or 2;
m is 0, 1, 2, 3, 4 or 5;
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;
R 3 is hydrogen or —(CH 2 ) g OH wherein g is 0, 1 or 2;
R 4 is hydrogen, methyl or ethyl;
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
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 pharmaceutically acceptable salt of the compound.
8. The method of claim 7 , wherein the compound is represented by the formula
wherein A, R 1 , R 2 , R 3 , R 4 , t, q, n, and m have the values set forth in claim 7 .
9. The method of claim 8 , wherein m is 1; n is 1; q is 0; t is 0; R 2 is hydrogen; R 4 is hydrogen; 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.
10. The method of claim 9 , wherein A is 2,6-dimethylphenyl.
11. The method of claim 10 , wherein the compound is N-Hydroxy-2-[3-(2,6-dimethylbenzyloxy)phenyl]acetamide.
12. The method of claim 10 , wherein the compound is 2-[3-(2,6-Dimethylbenzyloxy)phenyl]acetamide.
13. The method of claim 10 , wherein the compound is N-(2-Hydroxyethyl)-2-[3-(2,6-dimethylbenzyloxy)phenyl]acetamide.
14. The method of claim 7 , wherein the subject is a human.
15. The method of claim 14 , wherein the compound or salt is administered orally in an amount from one milligram to four hundred milligrams per day.
16. The method of claim 7 , wherein the condition is insulin resistance syndrome or Type II Diabetes.
17. A pharmaceutical composition adapted for oral administration, comprising a pharmaceutically acceptable carrier and from one milligram to four hundred milligrams of a compound of the formula:
wherein
n is 1 or 2;
m is 1, 2, 3, 4 or 5;
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;
R 3 is hydrogen or —(CH 2 ) g OH wherein g is 0, 1 or 2;
R 4 is hydrogen, methyl or ethyl;
A is 2,6-dimethylphenyl;
or a pharmaceutically acceptable salt of the compound.
18. The pharmaceutical composition of claim 17 , wherein the compound is represented by the formula
wherein A, R 1 , R 2 , R 3 , R 4 , t, q, n, and m have the values set forth in claim 17 .
19. The pharmaceutical composition of claim 18 , wherein m is 1; n is 1; q is 0; t is 0; R 2 is hydrogen; and R 4 is hydrogen.
20. The pharmaceutical composition of claim 19 , wherein the compound is N-Hydroxy-2-[3-(2,6-dimethylbenzyloxy)phenyl]acetamide.
21. The pharmaceutical composition of claim 19 , wherein the compound is 2-[3-(2,6-Dimethylbenzyloxy)phenyl]acetamide.
22. The pharmaceutical composition of claim 19 , wherein the compound is N-(2-Hydroxyethyl)-2-[3-(2,6-dimethylbenzyloxy)phenyl]acetamide.
23. The pharmaceutical composition of claim 17 in oral dosage form.