Oxotetrahydrofuran-2-yl-benzimidazole derivative
The present invention relates to compounds, which are useful for treatment and/or prevention of diabetes mellitus, diabetes mellitus complications or obesity, since the compounds have glucokinase-activating effects, and are presented in Formula (I): wherein R1 represents a carbamoyl group; R2 represents a lower alkyl group; both of X1 and X2 represent CH, or any one of X1 and X2 represents a nitrogen atom and the other represents CH; a group of represents a group selected from the group consisting of a pyridinyl, a pyrazinyl, a pyrazolyl, a thiadiazolyl, a triazolyl, an isoxazolyl and a thiazolyl group; and k is zero or 1, or relates to pharmaceutically acceptable salts thereof.
1. A compound of formula (I), or a pharmaceutically acceptable salt thereof:
wherein R 1 is Formula (II):
wherein R 12 and R 13 independently represent a hydrogen atom or a lower alkyl group;
R 14 represents a lower alkyl group optionally having 1 to 4, the same or different hydroxy groups, lower alkoxy groups or halogen atoms;
m represents zero or 1;
n represents zero or 1; and
both of X 1 and X 2 represent CH; and
a group of Formula (IV):
which represents a pyridinyl group;
R 2 represents a lower alkyl group optionally substituted with a hydroxy group, a lower alkoxy group, or a hydroxy group; and
k represents zero or 1.
2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is a group of Formula (II-2):
wherein each symbol has the meaning provided in claim 1 .
3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is a group of (II-3):
—R 14 (II-3)
wherein each symbol has the meaning provided in claim 1 .
4. The compound of claim for a pharmaceutically acceptable salt thereof, wherein R 1 is a methoxymethyl group.
5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is a dimethylcarbamoylmethyl group or a methylcarbamoylmethyl group.
6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein m is 1.
7. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein k is zero.
8. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound of Formula (I) is selected from the group consisting of:
N,N-dimethyl-2-(4-{[6-(5-oxotetrahydrofuran-2-yl)-2-pyridin-2-yl-1H-benzimidazol-5-yl]oxy}phenyl)acetamide, and
N-methyl-2-(4-{[6-(5-oxotetrahydrofuran-2-yl)-2-pyridin-2-yl-1H-benzimidazol-5-yl]oxy}phenyl)acetamide.
9. A method for treating diabetes mellitus comprising administering a compound of claim 1 or a pharmaceutically acceptable salt thereof in an amount effective for the treatment of diabetes mellitus, and a pharmaceutically acceptable carrier.
10. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.