Pharmaceutical composition for treating diabetes
Provided is a compound represented by the following general formula (I), or a pharmaceutically acceptable salt thereof. This novel compound has a glycogen-synthase activation ability, but activates a receptor PPAR to a low degree and is highly safe. In the formula, Ar is an aromatic carbocyclic ring or a heterocyclic ring; and Ar 2 is represented by any one of the following rings and the like.
1. A compound of formula (I):
wherein Ar is an aromatic carbocyclic ring or a heterocyclic ring;
Ar 2 is represented by any one of the following rings
these rings may have a substituent, and
the substituent is selected from the group consisting of acetamido, aminocarbonyl, benzyl, benzyloxy, a halogen, hydroxyl-lower alkyl, lower alkyl, lower alkoxy-lower alkyl, phenoxy, phenyl, a formyl group, a cyano group, a cyanoalkyl group, a hydroxyiminomethyl group, a hydroxyamidino group, an amino group, an aminoalkyl group, an alkylaminoalkyl group, a dialkylaminoalkyl group, lower alkoxy, and trifluoro-methoxy;
R 2 and R 3 are independently selected from the group consisting of lower alkyl, lower alkoxy, trifluoromethyl, a halogen, hydroxy, a hydroxyl-lower alkyl group, amino, alkylamino, dialkylamino, cyano, and nitro;
R 4 is an amino acid residue bonded to C(O) through a nitrogen atom of the amino acid;
m is 0, 1, 2, 3, or 4;
p is 0, 1, or 2; and
s is 0, 1, or 2,
or a pharmaceutically acceptable salt thereof.
2. A compound of formula (I):
wherein Ar is an aromatic carbocyclic ring or a heterocyclic ring;
Ar 2 is represented by any one of the following rings
these rings may have a substituent, and
the substituent is selected from the group consisting of acetamido, aminocarbonyl, benzyl, benzyloxy, a halogen, hydroxyl-lower alkyl, lower alkyl, lower alkoxy-lower alkyl, phenoxy, phenyl, lower alkoxy, and trifluoro-methoxy;
R 2 and R 3 are independently selected from the croup consisting of lower alkyl, lower alkoxy, trifluoromethyl, a halogen, hydroxy, amino, alkylamino, dialkylamino, cyano, and nitro;
R 4 is an amino acid residue bonded to C(O) through a nitrogen atom of the amino acid;
m is 0, 1, 2, 3, or 4;
p is 0, 1, or 2; and
s is 0, 1, or 2,
or a pharmaceutically acceptable salt thereof.
3. The compound according to claim 2 , wherein Ar 2 in the formula (I) is represented by an one of the following rings
or a pharmaceutically acceptable salt thereof.
4. The compound according to claim 2 , wherein in the formula (I),
Ar is a phenyl group, and
R 4 represents a proline residue bonded to C(O) through a nitrogen atom of the proline,
or a pharmaceutically acceptable salt thereof.
5. The compound according to claim 2 , wherein in the formula (I),
Ar is a phenyl group,
R 4 represents a proline residue bonded to C(O) through a nitrogen atom of the proline, and
Ar 2 is represented by any one of the following rings which may have a substituent
or a pharmaceutically acceptable salt thereof.
6. The compound according to claim 5 , wherein the substituent Ar 2 in the formula (I) is a halogen,
or a pharmaceutically acceptable salt thereof.
7. The compound according to claim 6 , wherein, in the formula (I), m=0, p=0, and s=0,
or a pharmaceutically acceptable salt thereof.
8. A pharmaceutical composition, comprising:
the compound according to claim 1 or a pharmaceutically acceptable salt thereof, and
a pharmaceutically acceptable carrier.
9. A pharmaceutical composition, comprising:
the compound according to claim 2 or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable carrier.
10. A method of treating diabetes by glycogen-synthase activation, comprising:
administering an effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt thereof to a subject in need thereof.
11. A method of treating diabetes by a glycogen synthase activation, comprising:
administering an effective amount of the compound according to claim 2 or a pharmaceutically acceptable salt to a subject in need thereof.
12. A method or treating Type II diabetes, comprising:
administering an effective amount of the compound according to claim 1 or a pharmaceutically acceptable salt thereof to a subject in need thereof.
13. A method of treating Type II diabetes, comprising:
administering an effective amount of the compound according to claim 2 or a pharmaceutically acceptable salt to a subject in need thereof.