METHODS AND COMPOSITIONS FOR TREATMENT OF DIABETES AND DYSLIPIDEMIA
Novel compounds of Formula A1 are provided: its stereoisomers and/or pharmaceutically acceptable salts for the treatment of diabetes and diabetes-associated dyslipidemia, wherein R 7 is independently selected from a group consisting of hydroxy, alkoxy, alkyl, amine, NHR′ wherein R′ is alkyl or cycloalkyl optionally substituted by hydroxy or alkoxy, NHSO 2 R or NHCOR, wherein R is selected from alkyl or cycloalkyl. At least one of R 3 and R 4 and/or R 5 and R 6 form a cyclic ring of 3-8 carbon atoms optionally containing alkyl groups, hetero atoms, or functional groups such as O, N, SO 2 . Additionally R 3 and R 4 or R 5 and R 6 , when they do not form a cyclic ring, are independently selected from hydrogen, alkyl, branched alkyl, and cycloalkyl. L 1 is independently a linear aliphatic chain optionally containing from 6 to 16 carbon-atoms and L 1 may optionally be substituted one or more times by alkyl, branched alkyl, cycloalkyl, or aryl.
1 . A composition comprising at least one compound according to Formula A1
its stereoisomers and/or pharmaceutically acceptable salts, wherein:
R2 is selected from a group consisting of hydrogen, alkoxy, hydroxy, alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, heteroaryl, or COR 7 ; wherein R 7 is selected from a group consisting of hydroxy, alkyl, alkoxy, amine, NHR′, or NHSO 2 R.
n 1 is selected from 0, 1 or 2;
at least one of R 3 and R 4 and/or R 5 and R 6 form a cyclic ring of 3-8 carbon atoms optionally containing alkyl groups, hetero atoms, or functional groups such as O, N, SO 2 ;
R 3 and R 4 or R 5 and R 6 , when they do not form a cyclic ring, are independently selected from hydrogen, alkyl, branched alkyl, and cycloalkyl;
L 1 is a linear aliphatic chain optionally containing from 4 to 16 carbon atoms, optionally substituted one or more times by alkyl, branched alkyl, cycloalkyl, or aryl;
R 8 is an alkyl or branched containing 1-5 carbon atoms
R 9 is hydrogen or methyl group
2 . A composition according to claim 1 , wherein the compound is according to Formula A2:
its stereoisomers and/or pharmaceutically acceptable, wherein:
R 7 is independently selected from a group consisting of hydroxy, alkoxy, alkyl, amine, NHR′ wherein R′ is alkyl or cycloalkyl optionally substituted by hydroxy or alkoxy, NHSO 2 R or NHCOR, wherein R is selected from alkyl or cycloalkyl;
at least one of R 3 and R 4 and/or R 5 and R 6 form a cyclic ring of 3-8 carbon atoms optionally containing alkyl groups, hetero atoms, or functional groups such as O, N, SO 2 ;
R 3 and R 4 or R 5 and R 6 , when they do not form a cyclic ring, are independently selected from hydrogen, alkyl, branched alkyl, and cycloalkyl;
L 1 is independently a linear aliphatic chain optionally containing from 6 to 16 carbon-atoms and L 1 may optionally be substituted one or more times by alkyl, branched alkyl, cycloalkyl, or aryl.
3 . The composition according to claim 1 , wherein the compound is selected from one or more of:
their stereoisomers, pharmaceutically acceptable salts, tautomers, and mixtures thereof.
4 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound according to claim 1 .
5 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound according to claim 2 .
6 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and at least one compound according to claim 3
7 . A method for the treatment of insulin resistance, diabetes, and/or cardiovascular disease in a subject, the method comprising administering to the subject at least one compound according to Formula A1:
its stereoisomers and/or pharmaceutically acceptable salts, wherein:
R2 is selected from a group consisting of hydrogen, alkoxy, hydroxy, alkyl, haloalkyl, cycloalkyl, heterocycloalkyl, heteroaryl, or COR 7 ; wherein R 7 is selected from a group consisting of hydroxy, alkyl, alkoxy, amine, NHR′, or NHSO 2 R,
n 1 is selected from 0, 1 or 2;
at least one of R 3 and R 4 and/or R 5 and R 6 form a cyclic ring of 3-8 carbon atoms optionally containing alkyl groups, hetero atoms, or functional groups such as O, N, SO 2 ;
R 3 and R 4 or R 5 and R 6 , when they do not form a cyclic ring, are independently selected from hydrogen, alkyl, branched alkyl, and cycloalkyl;
L 1 is a linear aliphatic chain optionally containing from 4 to 16 carbon atoms, optionally substituted one or more times by alkyl, branched alkyl, cycloalkyl, or aryl;
R 8 is an alkyl or branched containing 1-5 carbon atoms
R 9 is hydrogen or methyl group
8 . The method according to claim 7 , wherein the method comprises administering to the subject a compound according to Formula A2:
its stereoisomers and/or pharmaceutically acceptable, wherein:
R 7 is independently selected from a group consisting of hydroxy, alkoxy, alkyl, amine, NHR′ wherein R′ is alkyl or cycloalkyl optionally substituted by hydroxy or alkoxy, NHSO 2 R or NHCOR, wherein R is selected from alkyl or cycloalkyl;
at least one of R 3 and R 4 and/or R 5 and R 6 form a cyclic ring of 3-8 carbon atoms optionally containing alkyl groups, hetero atoms, or functional groups such as O, N, SO 2 ;
R 3 and R 4 or R 5 and R 6 , when they do not form a cyclic ring, are independently selected from hydrogen, alkyl, branched alkyl, and cycloalkyl;
L 1 is independently a linear aliphatic chain optionally containing from 6 to 16 carbon-atoms and L 1 may optionally be substituted one or more times by alkyl, branched alkyl, cycloalkyl, or aryl.
9 . The method according to claim 7 , wherein the method comprises administering to the subject a compound selected from one or more of:
their stereoisomers, pharmaceutically acceptable salts, tautomers, and mixtures thereof.
10 . The composition according to claim 1 , wherein the compound is selected from one or more of:
their stereoisomers, pharmaceutically acceptable salts, tautomers, and mixtures thereof.
11 . The method according to claim 7 , wherein the method comprises administering to the subject a compound selected from one or more of:
their stereoisomers, pharmaceutically acceptable salts, tautomers, and mixtures thereof.