Small molecule insulin mimetics absent quinones
Compounds of Formula I are described along with pharmaceutical formulations thereof, and methods of treating disorders such as diabetes and neurodegenerative diseases with such compounds.
1. A method of treating diabetes in a subject in need thereof, comprising administering to said subject a compound of Formula I:
wherein:
n is 1, 2, 3 or 4;
R 1 is selected from the group consisting of O, S, N-alkyl, N-cycloalkyl, N-aryl, and CR 2 where each R is independently selected from the group consisting of H, alkyl, alkenyl, cycloalkyl, and aryl;
each R 2 is independently selected from the group consisting of alkyl, alkenyl, phenylalkyl, and phenylalkyloxy;
R 3 is selected from the group consisting of H and alkyl;
R 4 is selected from the group consisting of H and alkyl;
R 5 is selected from the group consisting of H, alkyl, and hydroxyalkyl; and
R 6 is selected from the group consisting of H, alkyl, and hydroxyalkyl;
or a pharmaceutically acceptable salt or prodrug thereof in an amount effective to treat said diabetes.
2. A method of claim 1 , wherein:
n is 1 or 2;
R 1 is O, S, or N-alkyl;
each R 2 is independently selected from the group consisting of alkyl and alkenyl; phenylalkyl, and phenylalkyloxy;
R 3 is selected from the group consisting of H and alkyl;
R 4 is selected from the group consisting of H and alkyl;
R 5 is selected from the group consisting of H, alkyl, and hydroxyalkyl; and
R 6 is selected from the group consisting of H, alkyl, and hydroxyalkyl;
or a pharmaceutically acceptable salt or prodrug thereof.
3. The method of claim 1 , wherein said diabetes is selected from the group consisting of type I diabetes, type II diabetes, gestational diabetes, and pre-diabetes.
4. The method of claim 1 , wherein said administering step is an oral administration step.
5. A method of treating diabetes in a subject in need thereof, comprising administering to said subject a compound of Formula Ia:
wherein:
R 1 is selected from the group consisting of O, S, N-alkyl, N-cycloalkyl, N-aryl, and CR 2 where each R is independently selected from the group consisting of H, alkyl, alkenyl, cycloalkyl, and aryl;
each R 2 is independently selected from the group consisting of alkyl, alkenyl, phenylalkyl, and phenylalkyloxy;
R 3 is selected from the group consisting of H and alkyl;
R 4 is selected from the group consisting of H and alkyl;
R 5 is selected from the group consisting of H, alkyl, and hydroxyalkyl; and
R 6 is selected from the group consisting of H, alkyl, and hydroxyalkyl;
or a pharmaceutically acceptable salt or prodrug thereof, in an amount effective to treat said diabetes.
6. The method of claim 5 , wherein:
R 1 is O or N-alkyl,
R 2 is alkenyl,
R 3 is H;
R 4 is H;
R 5 is hydroxyalkyl;
R 6 is H;
or a pharmaceutically acceptable salt or prodrug thereof.
7. A method of claim 5 , said compound selected from the group consisting of:
and pharmaceutically acceptable salts or prodrugs thereof.
8. The method of claim 5 , wherein said diabetes is selected from the group consisting of type I diabetes, type II diabetes, gestational diabetes, and pre-diabetes.
9. The method of claim 5 , wherein said administering step is an oral administration step.
10. A method of treating diabetes in a subject in need thereof, comprising orally administering to said subject a compound selected from the group consisting of:
and pharmaceutically acceptable salts or prodrugs thereof.
11. A method of treating diabetes in a subject in need thereof, comprising administering to said subject a compound of Formula I:
wherein:
n is 1, 2, 3 or 4;
R 1 is selected from the group consisting of O, S, N-alkyl, N-cycloalkyl, N-aryl, and CR 2 where each R is independently selected from the group consisting of H, alkyl, alkenyl, cycloalkyl, and aryl;
each R 2 is independently selected from the group consisting of alkyl, alkenyl, phenylalkyl, and phenylalkyloxy;
R 3 is selected from the group consisting of H and alkyl;
R 4 is selected from the group consisting of H and alkyl;
R 5 is selected from the group consisting of H, alkyl, and hydroxyalkyl; and
R 6 is selected from the group consisting of H, alkyl, and hydroxyalkyl;
or a pharmaceutically acceptable salt thereof in an amount effective to treat said diabetes, wherein said compound mimics the action of insulin.
12. A method of claim 11 , wherein:
n is 1 or 2;
R 1 is O, S, or N-alkyl;
each R 2 is independently selected from the group consisting of alkyl and alkenyl; phenylalkyl, and phenylalkyloxy;
R 3 is selected from the group consisting of H and alkyl;
R 4 is selected from the group consisting of H and alkyl;
R 5 is selected from the group consisting of H, alkyl, and hydroxyalkyl; and
R 6 is selected from the group consisting of H, alkyl, and hydroxyalkyl;
or a pharmaceutically acceptable salt thereof.
13. The method of claim 11 , wherein said diabetes is selected from the group consisting of type I diabetes, type II diabetes, gestational diabetes, and pre-diabetes.
14. The method of claim 13 , wherein said diabetes is type I diabetes.
15. The method of claim 11 , wherein said administering step is an oral administration step.
16. A method of claim 11 , wherein the compound is a compound of Formula Ia:
17. The method of claim 16 , wherein said diabetes is selected from the group consisting of type I diabetes, type II diabetes, gestational diabetes, and pre-diabetes.
18. The method of claim 17 , wherein said diabetes is type I diabetes.
19. A method of treating diabetes in a subject in need thereof, comprising orally administering to said subject a compound selected from the group consisting of:
and pharmaceutically acceptable salts thereof, wherein said compound mimics the action of insulin.
20. The method of claim 19 , wherein said diabetes is type I diabetes.