Aryloxy-substituted benzimidazole derivatives

1. A compound of a formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

R 1 and R 2 each independently represent a hydrogen atom, a halogen atom, a lower alkyl group, a hydroxyl group, a cyano group or a lower alkoxy group;

R 3 independently represents a hydrogen atom, a halogen atom, a lower alkyl group, a lower alkoxy group, a hydroxyalkyl group, a trifluoromethyl group, a lower alkenyl group or a cyano group;

R 4 independently represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, a halogen atom, a trifluoromethyl group, a hydroxyalkyl group optionally substituted with a lower alkyl group, an aminoalkyl group optionally substituted with a lower alkyl group, an alkanoyl group, a carboxyl group, a lower alkoxycarbonyl group or a cyano group;

Q represents a carbon atom, a nitrogen atom or a sulfur atom optionally substituted with one or two oxo groups;

R 5 and R 6 each independently represent a hydrogen atom, a lower alkyl group, a halogen atom, a lower alkyl group, a lower alkylsulfonyl group, a lower alkylsulfinyl group, an alkanoyl group, a formyl group, an aryl group, a mono- or di-lower alkylcarbamoyl group or a mono- or di-lower alkylsulfamoyl group; or taken together, Q, R 5 and R 6 may form the following:

(A) a 5- or 6-membered aliphatic nitrogen-containing heterocyclic group optionally having, in the ring thereof, from 1 to 3 hetero atoms selected from the group consisting of a nitrogen atom, a sulfur atom and an oxygen atom, and having at least one nitrogen atom in addition to the hetero atoms;

said heterocyclid group may have one or two double bonds;

(B) a 5- or 6-membered aromatic nitrogen-containing heterocyclic group optionally having, in the ring thereof, from 1 to 3 hetero atoms selected from the group consisting of a nitrogen atom, a sulfur atom and an oxygen atom, and having at least one nitrogen atom in addition to the hetero atoms, or

(C) a phenyl group,

and the aliphatic nitrogen-containing heterocyclic group, the aromatic nitrogen-containing heterocyclic group or the phenyl group may have from 1 to 3 groups selected from the following substituent group a, and/or may have, as the substituent thereof, a 3- to 6-membered ring formed through bonding to each other of the bondable groups selected from the substituent group α, and/or may be condensed with a group of a formula (A):

wherein  represents a single bond or a double bond;

X 1 , X 2 , X 3 and X 4 each independently represent a carbon atom or a nitrogen atom;

Z represents an oxygen atom;

Ar represents a pyridyl group optionally substituted with from 1 to 3 groups selected from the following substituent group β;

ring A represents a pyridyl ring of a formula (III):

wherein X represents a carbon atom;

m indicates an integer of from 1 to 6;

n indicates an integer of from 0 to 3;

p indicates an integer of from 0 to 2; provided that at least two of X 1 to X 4 are hydrogen atoms;

q indicates 0 or 1;

Substituent groupα:

an oxo group, a thioxo group, a lower alkyl group, a lower alkoxy group, an alkanoyl group, a formyl group, a hydroxy group, a carboxyl group, a trifluoromethyl group, a hydroxyalkyl group optionally substituted with a lower alkyl group, a cyano group, a mono- or di-lower alkylcarbamoyl group, a lower alkylsulfinyl group, a lower alkylsulfonyl group and a halogen atom;

Substituent group β:

a lower alkyl group, a lower alkoxy group, a halogen atom, a trifluoromethyl group, a hydroxyalkyl group optionally substituted with a lower alkyl group, a lower alkylsulfonyl group, a lower alkylsulfanyl group, a lower alkylsulfinyl group, an aminoalkyl group optionally substituted with a lower alkyl group, an alkanoyl group, a carboxyl group, a mono- or di-lower alkylcarbamoyl group, a mono- or di-lower alkylsulfamoyl group, a lower alkoxycarbonyl group, a cyano group, an aryl group, and a heteroaryl group, having in the ring thereof, from 1 to 3 hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom;

said aryl group and heteroaryl group may have one or two groups selected from the following substituent group γ;

Substituent group γ:

a lower alkyl group, a lower alkoxy group, a halogen atom, a hydroxyl group, a lower alkylsulfonyl group, a lower alkylsulfinyl group, an alkanoyl group, a cyano group, a mono-or di-lower alkylcarbamoyl group.

2. The compound or a pharmaceutically acceptable salt according to claim 1 , wherein m is from 1 to 4.

3. The compound or a pharmaceutically acceptable salt according to claim 1 , wherein R 5 and R 6 each independently represent a hydrogen atom, a lower alkyl group, a halogen atom, a lower alkyl group, a lower alkylsulfonyl group, a lower alkylsulfonyl group, an alkanoyl group or a formyl group.

4. The compound or a pharmaceutically acceptable salt according to claim 1 , wherein Q is a nitrogen atom.

5. The compound or a pharmaceutically acceptable salt according to claim 1 , wherein Q is a carbon atom.

6. The compound or a pharmaceutically acceptable salt according to claim 1 , wherein the group of a formula (I-A):

in the formula (I-1) is a group of the following formula:

wherein: R 11 represents a hydrogen atom or a lower alkyl group; and the other symbols have the same meanings as above.

7. The compound or a pharmaceutically acceptable salt according to claim 1 , wherein:

Q is a nitrogen atom;

R 5 and R 6 , taken together with the nitrogen atom, form a 5- or 6-membered aliphatic nitrogen-containing heterocyclic group optionally having, in the ring thereof, from 1 to 3 hetero atoms selected from the group consisting of a nitrogen atom, a sulfur atom and an oxygen atom, and having at least one nitrogen atom in addition to the hetero atoms;

said 5- or 6- membered aliphatic nitrogen-containing heterocyclic group may have one or two double bonds, an may be mono- or di-substituted with the same or different groups selected from the following substituent group α1;

m is 1;

Z is an oxygen atom;

Ar is a pyridyl group optionally mono- or di-substituted with the same or different groups selected from the following substituent group β1;

R 1 and R 2 are independently a hydrogen atom or a lower alkyl group, Substituent group α1:

an oxo group, a thioxo group, a lower alkyl group, a lower alkoxy group, an alkanoyl group, a halogen atom, a cyano group, a mono- or di-lower alkylcarbamoyl group;

Substituent group β1:

a lower alkyl group, a lower alkoxy group, a halogen atom, a trifluoromethyl group, a hydroxyalkyl group optionally substituted with a lower alkyl group, a lower alkylsulfonyl group, an alkanoyl group, a carboxyl group, a mono- or di-lower alkylcarbamoyl group, a mono- or di-lower alkylsulfamoyl group, a lower alkoxycarbonyl group, a cyano group, an aryl group, or a heteroaryl group having, in the ring thereof, 2 or 3 hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom;

said aryl group and the heteroaryl group may have one or two groups selected from the substituent group γ.

8. The compound or its pharmaceutically-acceptable salt according to claim 1 , wherein: Q, R 5 and R 6, taken together, form a 5- or 6-membered aromatic nitrogen-containing heterocyclic group having at least one nitrogen atom, optionally having in the ring from 1 to 3 hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom in addition to that nitrogen atom, or a phenyl group;

said aromatic heterocyclic group or the phenyl group may have from 1 to 3 groups selected from the following substituent group α2;

Z is an oxygen atom;

Ar is a pyridyl group optionally mono- or di-substituted with the same or different groups selected from the following substituent group β1;

R 1 and R 2 are independently a hydrogen atom or a lower alkyl group;

Substituent group α2:

a hydroxyl group, a lower alkyl group, a lower alkoxy group, an alkanoyl group, a halogen atom, a cyano group and a mono- or di-lower alkylcarbamoyl group;

Substituent group β1:

a lower alkyl group, a lower alkoxy group, a halogen atom, a trifluoromethyl group, a hydroxyalkyl group optionally substituted with a lower alkyl group, a lower alkylsulfonyl group, an alkanoyl group, a carboxyl group, a mono- or di-lower alkylcarbamoyl group, a mono- or di-lower alkylsulfamoyl group, a lower alkoxycarbonyl group, a cyano group, an aryl group, or a heteroaryl group having, in the ring thereof, 2 or 3 hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom;

said aryl group and the heteroaryl group may have one or two groups selected from the substituent group γ.

9. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein: the formula (I) is selected from the group consisting of:

1-{[5-{[6-(ethylsulfonyl)-3-pyridinyl]oxy}-2-(2-pyridinyl)-1H-benzimidazol-6-yl]methyl}pyrrolidine-2,5-dione,

1-[(5-{[6-(5-methyl-1,2,4-oxadiazol-3-yl)-3-pyridinyl]oxy}-2-(2-pyridinyl)-1H-benzimidazol-6-yl)methyl]-2-pyrrolidinone, and

1-[(6-{[6-(ethylsulfonyl)pyridin-3-yl]oxy}-2-pyridin-2-yl-1H-benzimidazol-4-yl)methyl]pyrrolidin-2-one.

10. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the formula (I) is 1-{[5-{[6-(ethylsulfonyl)-3-pyridinyl]oxy}-2-(2-pyridinyl)-1H-benzimidazol-6-yl]methyl}pyrrolidine-2,5-dione.

11. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the formula (I) is 1-[(5-{[6-(5-methyl-1,2,4-oxadiazol-3-yl)-3-pyridinyl]oxy}-2-(2-pyridinyl)-1H-benzimidazol-6-yl)methyl]-2-pyrrolidinone.

12. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the formula (I) is 1-[(6-{[6-(ethylsulfonyl)pyridin-3-yl]oxy}-2-pyridin-2-yl-1H-benzimidazol-4-yl)methyl]pyrrolidin-2-one.

13. A pharmaceutical composition comprised of a compound in accordance with claim 1 in combination with a phamaceutically acceptable carrier.

14. A method of treating type 2 diabetes in a mammialian patient, comprising administering to said patient a compound in accordance with claim 1 in an amount effective to treating type 2 diabetes.