Triazole compounds and uses related thereto

1. A method for the treatment of diabetes, which comprises administering to a mammal an effective amount of a triazole compound of the following formula:

wherein

R 1 is an alkyl group or a cycloalkyl group wherein the alkyl group and the cycloalkyl group are optionally substituted by 1 to 5 substituents each independently selected from a halogen atom, —CF 3 , —OH, —NH 2 , an alkoxy group, a cycloalkyl group, an alkenyl group, —COOH, —CO—O-alkyl, —CO—N(R 7 )(R 8 ), —N(R 7 )—CO—R 8 , an aryl group and a heteroaryl group

wherein R 7 and R 8 are each independently a hydrogen atom or an alkyl group, and the aryl group and the heteroaryl group are optionally substituted by 1 to 3 substituents each independently selected from a halogen atom, a haloalkyl group, an alkyl group, —(CH 2 ) n —OH, —N(R 9 )(R 10 ), —CN, —NO 2 , an alkoxy group, a cycloalkyl group, an alkenyl group, —CO—R 11 , an aryl group and a heteroaryl group

wherein n is 0-3, R 9 and R 10 are each independently a hydrogen atom, an alkyl group or —CO-alkyl, and R 11 is —OH, an alkoxy group, an alkyl group or —N(R 12 )(R 13 ) wherein R 12 and R 13 are each independently a hydrogen atom or an alkyl group;

Y is a cycloalkyl group or a heterocycloalkyl group

wherein the cycloalkyl group and the heterocycloalkyl group are optionally substituted by 1 to 3 substituents each independently selected from a halogen atom, a haloalkyl group, an alkyl group, —(CH 2 ) n —OH, —N(R 9 )(R 10 ), —CN, —NO 2 , an alkoxy group, a cycloalkyl group, an alkenyl group, —CO—R 11 , an aryl group and a heteroaryl group (n, R 9 , R 10 and R 11 are as defined above);

Ar 1 is an aryl group or a heteroaryl group;

R 2 and R 3

are each independently a hydrogen atom, a halogen atom, a haloalkyl group, an alkyl group, —(CH 2 ) n —OH, —N(R 9 )(R 10 ), —CN, —NO 2 , an alkoxy group, a cycloalkyl group, an alkenyl group, —CO—R 11 , an aryl group or a heteroaryl group

wherein the aryl group and the heteroaryl group are optionally substituted by 1 to 3 substituents each independently selected from a halogen atom, a haloalkyl group, an alkyl group, —(CH 2 ) n —OH, —N(R 9 )(R 10 ), —CN, —NO 2 , an alkoxy group, a cycloalkyl group, an alkenyl group, —CO—R 11 , an aryl group and a heteroaryl group (n, R 9 , R 10 and R 11 are as defined above);

Z is —(CH(R 14 )) p —, —(CH(R 14 )) p —N(R 16 )—(CH(R 15 )) q — or

wherein Y, is a cycloalkyl group or a heterocycloalkyl group

wherein the cycloalkyl group and the heterocycloalkyl group are optionally substituted by 1 to 3 substituents each independently selected from a halogen atom, a haloalkyl group, an alkyl group, —(CH 2 ) n —OH, —N(R 9 )(R 10 ), —CN, —NO 2 , an alkoxy group, a cycloalkyl group, an alkenyl group, —CO—R 11 , an aryl group and a heteroaryl group (n, R 9 , R 10 and R 11 are as defined above),

p is 0-3, q is 0-3, R 14 and R 15 are each independently a hydrogen atom, a halogen atom, a haloalkyl group, an alkyl group, —(CH 2 ) n —OH, —N(R 9 )(R 10 ), —CN, —NO 2 , an alkoxy group, a cycloalkyl group, an alkenyl group, —CO—R 11 , an aryl group or a heteroaryl group

wherein the aryl group and the heteroaryl group are optionally substituted by 1 to 3 substituents each independently selected from a halogen atom, a haloalkyl group, an alkyl group, —(CH 2 ) n —OH, —N(R 9 )(R 10 ), —CN, —NO 2 , an alkoxy group, a cycloalkyl group, an alkenyl group, —CO—R 11 , an aryl group and a heteroaryl group (n, R 9 , R 10 and R 11 are as defined above), and

R 16 is a hydrogen atom, a haloalkyl group, an alkyl group, —(CH 2 ) n —OH, —(CH 2 ) n —CO—R 11 , a cycloalkyl group, an alkenyl group, an aryl group or a heteroaryl group

wherein the aryl group and the heteroaryl group are optionally substituted by 1 to 3 substituents each independently selected from a halogen atom, a haloalkyl group, an alkyl group, —(CH 2 ) n —OH, —N(R 9 )(R 10 ), —CN, —NO 2 , an alkoxy group, a cycloalkyl group, an alkenyl group, —CO—R 11 , an aryl group and a heteroaryl group (n, R 9 , R 10 and R 11 are as defined above);

Ar 2 is an aryl group, a heteroaryl group or

wherein X 1 is —(CH 2 ) t — wherein t is 0-2, V 1 is ═CH— or ═N—, and W 1 is —C(R 17 )(R 18 )—, —O—, —S—, —SO 2 —, —SO—, —CO— or —N(R 19 )—

wherein R 17 and R 18 are each independently a hydrogen atom, an alkyl group, an alkoxy group, a haloalkyl group, —(CH 2 ) r —OH, —CO—R 20 , —N(R 21 )(R 22 ) or -L 1 -Ar 3

wherein r is 0-3, R 20 is —OH, an alkoxy group, an alkoxyalkyl group or —N(R 29 )(R 24 )

 wherein R 23 and R 24 are each independently a hydrogen atom, an alkyl group, —(CH 2 ) n —OH, an alkoxyalkyl group, or in combination form

 wherein s is 0-3, X 2 is —O—, —(CH 2 ) t — or —N(R 25 )—

 wherein t is as defined above and R 25 is a hydrogen atom, —CO—R 26 , —SO 2 —R 26 or —(CH 2 ) u —Ar 2

 wherein R 26 is an alkyl group, an alkoxy group, —NH-alkyl or —N(-alkyl) 2 , u is 0-3, and Ar 4 is an aryl group or a heteroaryl group wherein the aryl group and the heteroaryl group are optionally substituted by 1 to 3 substituents each independently selected from a halogen atom, a haloalkyl group, an alkyl group, —(CH 2 ) n —OH, —N(R 9 )(R 10 ), —CN, —NO 2 , an alkoxy group, a cycloalkyl group, an alkenyl group, —CO—R 11 , an aryl group and a heteroaryl group (n, R 9 , R 10 and R 11 are as defined above),

L 1 is —(CH 2 ) v —, —O— or —CO—

wherein v is 0-3, and

Ar 3 is an aryl group or a heteroaryl group wherein the aryl group and the heteroaryl group are optionally substituted by 1 to 3 substituents each independently selected from a halogen atom, a haloalkyl group, an alkyl group, —(CH 2 ) n —OH, —N(R 9 )(R 10 ), —CN, —NO 2 , an alkoxy group, a cycloalkyl group, an alkenyl group, —CO—R 11 , an aryl group and a heteroaryl group (n, R 9 , R 10 and R 11 are as defined above), and

R 21 and R 22 are each independently a hydrogen atom, an alkyl group, —CO-alkyl, —CO—O-alkyl or -L 1 -Ar 3 (L 1 and Ar 3 are as defined above), and

R 19 is a hydrogen atom, —CO—R 26 , —SO 2 —R 26 or —(CH 2 ) u —Ar 4 (R 26 , u and Ar 4 are as defined above); and

R 4 and R 5

are each independently a hydrogen atom, a halogen atom, —OH, —NO 2 , —CN, an alkyl group, an alkoxy group, —CO—R 27 , —SO 2 —R 27 , —CO—N(R 28 )(R 29 ) or —N(R 30 )(R 31 )

wherein the alkyl group and the alkoxy group are optionally substituted by 1 to 5 substituents each independently selected from a halogen atom, —CF 3 , —OH, an alkoxy group, a haloalkoxy group, —N(R 9 )(R 10 ), —CN, —NO 2 , a cycloalkyl group, an alkenyl group, —CO—R 11 , an aryl group and a heteroaryl group (R 9 , R 10 and R 11 are as defined above),

wherein the aryl group and the heteroaryl group are optionally substituted by 1 to 3 substituents each independently selected from a halogen atom, a haloalkyl group, an alkyl group, —(CH 2 ) n —OH, —N(R 9 )(R 10 ), —CN, —NO 2 , an alkoxy group, a cycloalkyl group, an alkenyl group, —CO—R 11 , an aryl group and a heteroaryl group (n, R 9 , R 10 and R 11 are as defined above)

R 27 is —OH, an alkoxy group, an alkyl group, —NH 2 , —NH-alkyl or —N(-alkyl) 2 ,

R 28 and R 29 are each independently a hydrogen atom, an alkyl group or —(CH 2 ) w —R 32 ,

wherein w is 0-3 and R 32 is —OH, —CF 3 , an alkoxy group, —CONH 2 or —N(R 33 )(R 34 )

 wherein R 33 and R 34 are each independently a hydrogen atom, an alkyl group, —CO-alkyl, or in combination form

 (X 2 is as defined above)

or R 28 and R 29 in combination form

wherein X 3 is —CO—, —CH 2 — or —CH 2 —CH 2 —, X 4 is

—O—, —(CH 2 ) t —, —N(R 25 )— or

 wherein Y 2 is cycloalkyl or heterocycloalkyl and t and R 25 are as defined above, and R 35 and R 36 are each independently a hydrogen atom, a halogen atom, an alkyl group optionally substituted by —OH, —OH, —CN, —NO 2 , an alkoxy group, a cycloalkyl group, an alkenyl group, —CO—R 37 , —N(R 38 )(R 39 )

 wherein R 37 is —OH, an alkoxy group, —NH 2 ,

 —NH-alkyl, —N(-alkyl) 2 or

 (X 2 is as defined above)

 wherein the alkyl group in —NH-alkyl and —N(-alkyl) 2 and the alkoxy group are optionally substituted by 1 to 5 substituents each independently selected from a halogen atom, —CF 3 , —OH, an alkoxy group, a haloalkoxy group, —N(R 9 )(R 10 ), —CN, —NO 2 , a cycloalkyl group, an alkenyl group, —CO—R 11 , an aryl group and a heteroaryl group (R 9 , R 10 and R 11 are as defined above),

 wherein the aryl group and the heteroaryl group are optionally substituted by 1 to 3 substituents each independently selected from a halogen atom, a haloalkyl group, an alkyl group, —(CH 2 ) n —OH, —N(R 9 )(R 10 ), —CN, —NO 2 , an alkoxy group, a cycloalkyl group, an alkenyl group, —CO—R 11 , an aryl group and a heteroaryl group (n, R 9 , R 10 and R 11 are as defined above), and

R 38 and R 39 are each independently a hydrogen atom, an alkyl group, —CO-alkyl or —CO—O-alkyl, and

R 10 and R 31 are each independently a hydrogen atom, an alkyl group optionally substituted by —OH, —SO 2 —

R 40 , —(CH 2 ) x —CO—R 41 or

wherein x is 0-3, R 40 is an alkyl group or —NH 2 , R 41 is a hydrogen atom, an alkyl group optionally substituted by —OH, —OH, an alkoxy group, an alkoxyalkyl group or —(CH 2 ) s —N(R 42 )(R 43 )

 wherein s is as defined above and R 42 and R 43 are each independently a hydrogen atom, an alkyl group, —OH, an alkoxy group, or in combination form

 (X 3 , X 4 , R 35 and R 36 are as defined above),

V 2 is ═CH— or ═N— and W 2 is —C (R 44 )(R 45 )—, —O— or —N(R 46 )—

 wherein R 44 and R 45 are each independently a hydrogen atom, an alkyl group, an alkoxy group, a haloalkyl group, —(CH 2 ) r —OH, —CO—R 47 or —N(R 48 )(R 49 )

 wherein r is as defined above, R 47 is —OH, an alkoxy group, an alkoxyalkyl group, —N(R 50 )(R 51 )

 wherein R 50 and R 51 are each independently a hydrogen atom, an alkyl group, —(CH 2 ) s —OH (s is as defined above) or an alkoxyalkyl group, and

 R 48 and R 49 are each independently a hydrogen atom, an alkyl group, —CO-alkyl or —CO—O-alkyl, and

 R 46 is a hydrogen atom, —CO—R 52 or —SO 2 —R 52

wherein R 52 is an alkyl group, an alkoxy group, —NH-alkyl or —N(-alkyl) 2 or

R 30 and R 31 in combination form

 (X 3 , X 4 , R 25 and R 36 are as defined above), or

R 4 and R 5 in combination may form —O-alkylene-O—,

a prodrug thereof or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , further comprising administering a therapeutic drug of diabetes that is different from the triazole compound.

3. The method of claim 2 , wherein the therapeutic drug of diabetes is one or more pharmaceutical agents selected from the group consisting of an insulin preparation, a sulfonylurea, an insulin secretagogue, a sulfonamide, a biguanide, an α-glucosidase inhibitor and an insulin sensitizer.

4. The method of claim 3 , wherein the therapeutic drug of diabetes is one or more pharmaceutical agents selected from the group consisting of insulin, glibenclamide, tolbutamide, glyclopyramide, acetohexamide, glimepiride, tolazamide, gliclazide, nateglinide, glybuzole, metformin hydrochloride, buformine hydrochloride, voglibose, acarbose and pioglitazone hydrochloride.

5. The method of claim 1 , further comprising administering a drug of obesity that is different from the triazole compound.

6. The method of claim 5 , wherein the therapeutic drug of obesity is Mazindol.