Anilinopyrazole derivatives useful for the treatment of diabetes

1. A compound of Formula (I)

wherein

R is H or (C 1 -C 6 )alkyl;

R 1 is H,

(C 1 -C 6 )alkyl optionally substituted with one substituent selected from the group consisting of (C 1 -C 4 )alkoxy, phenyl optionally substituted with halo, and [tri(C 1 -C 4 )alkyl]silyl,

(C 3 -C 6 )alkenyl,

(C 3 -C 6 )alkynyl,

(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl, CF 3 , and halo,

(C 1 -C 3 )haloalkyl, or

phenyl optionally substituted with up to four substituents selected from the group consisting of

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

NR 8 R 8 ,

cyano, and

(C 1 -C 6 )alkylthio;

R 2 is H,

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl and halo,

(C 1 -C 3 )haloalkyl,

phenyl optionally substituted with up to four substituents selected from the group consisting of

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

hydroxy,

NR 8 R 8 ,

cyano,

(C 1 -C 6 )alkylthio,

halo,

CO 2 R 8 ,

(C 1 -C 3 )haloalkoxy,

(C 1 -C 4 )acyl, and

benzoyl, or

tetrahydronaphthyl, or indanyl, each of which may be optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 6 )alkoxy, or

(C 1 -C 6 )alkythio, halo, and (C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy;

R 3 is (C 1 -C 6 )alkyl,

(C 3 -C 6 )cycloalkyl,

benzyl optionally substituted on the aryl ring with up to four substituents selected from the group consisting of

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

halo,

(C 1 -C 3 )haloalkyl,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkoxy,

NR 8 R 8 ,

cyano,

(C 1 -C 6 )alkylthio, and

SO 2 (C 1 -C 3 )alkyl,

(C 2 -C 3 )haloalkyl, or

phenyl optionally substituted with up to four substituents selected from the group consisting of

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

halo,

(C 1 -C 3 )haloalkyl,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkoxy

NR 8 R 8 ,

cyano,

(C 1 -C 6 )alkylthio, and

SO 2 (C 1 -C 3 )alkyl;

R 4 is (C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

(C 1 -C 6 )alkylthio,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

halo,

NR 8 R 8 ,

or

phenyl optionally substituted with up to four substituents selected from the group consisting of

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

NR 8 R 8 ,

cyano, and

(C 1 -C 6 )alkylthio;

n=0, 1, 2, or 3;

X is CO 2 R 8 , or CONR 5 R 6 ;

R 5 is H,

(C 1 -C 6 )alkyl,

(C 2 -C 6 )alkyl substituted with OR 6 ,

benzyl optionally substituted on the aryl ring with up to four substituents selected from the group consisting of

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

NR 8 R 8 ,

cyano, and

(C 1 -C 6 )alkylthio,

phenyl optionally substituted with up to four substituents selected from the group consisting of

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

halo,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

NR 8 R 8 ,

cyano, and

(C 1 -C 6 )alkylthio,

or

SO 2 -phenyl said phenyl optionally substituted with up to four substituents selected from the group consisting of

halo

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

NR 8 R 8 ,

cyano, and

(C 1 -C 6 )alkylthio;

R 6 is H or (C 1 -C 6 )alkyl;

R 7 is H or methyl;

R 8 is H,

(C 1 -C 6 )alkyl,

benzyl optionally substituted on the aryl ring with up to four substituents selected from the group consisting of

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 3 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

cyano, and

(C 1 -C 6 )alkylthio,

or

phenyl optionally substituted with up to four substituents selected from the group consisting of

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

halo,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

cyano, and

(C 1 -C 6 )alkylthio;

and pharmaceutically acceptable salts thereof;

provided that when R and R 2 are H and X is CO 2 H, then R 1 is not H, methyl, or ethyl, and further provided that the Formula (I) compound is not

2. The compound of claim 1 , wherein

R 1 is phenyl optionally substituted with up to four substituents selected from the group consisting of

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

NR 8 R 8 ,

cyano, and

(C 1 -C 6 )alkylthio;

and

R, R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X, and n are as defined in claim 1 .

3. The compound of claim 1 , wherein

R 2 is

phenyl optionally substituted with up to four substituents selected from the group consisting of

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

hydroxy,

NR 8 R 8 ,

cyano,

(C 1 -C 6 )alkylthio,

halo,

CO 2 R 8 ,

(C 1 -C 3 )haloalkoxy,

(C 1 -C 4 )acyl, and

benzoyl;

and

R, R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X, and n are as defined in claim 1 .

4. The compound of claim 1 , wherein

X is CO 2 R 8 ;

and

R, R 1 , R 2 , R 3 , R 4 , R 8 , and n are as defined in claim 1 .

5. The compound of claim 1 , wherein

R 1 is phenyl optionally substituted with up to four substituents selected from the group consisting of

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

NR 8 R 8 ,

cyano, and

(C 1 -C 6 )alkylthio;

R 2 is H,

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl and halo, or

(C 1 -C 3 )haloalkyl;

and

R, R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X, and n are as defined in claim 1 .

6. The compound of claim 1 , wherein

R 1 is H,

(C 1 -C 6 )alkyl optionally substituted with one substituent selected from the group consisting of (C 1 -C 4 )alkoxy, phenyl optionally substituted with halo, and [tri(C 1 -C 4 )alkyl]silyl,

(C 3 -C 6 )alkenyl,

(C 3 -C 6 )alkynyl,

(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl, CF 3 , and halo, or

(C 1 -C 3 )haloalkyl;

R 2 is H,

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl and halo, or

(C 1 -C 3 )haloalkyl;

and

R, R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X, and n are as defined in claim 1 .

7. The compound of claim 1 , wherein

R 1 is H,

(C 1 -C 6 )alkyl optionally substituted with one substituent selected from the group consisting of (C 1 -C 4 )alkoxy, phenyl optionally substituted with halo, and [tri(C 1 -C 4 )alkyl]silyl,

(C 3 -C 6 )alkenyl,

(C 3 -C 6 )alkynyl,

(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl, CF 3 , and halo, or

(C 1 -C 3 )haloalkyl;

R 2 is

phenyl optionally substituted with up to four substituents selected from the group consisting of

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

hydroxy,

NR 8 R 8 ,

cyano,

(C 1 -C 6 )alkylthio,

halo,

CO 2 R 8 ,

(C 1 -C 3 )haloalkoxy,

(C 1 -C 4 )acyl, and

benzoyl;

and

R, R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , X, and n are as defined in claim 1 .

8. The compound of claim 1 , wherein

R 1 is phenyl optionally substituted with up to four substituents selected from the group consisting of

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

NR 8 R 8 ,

cyano, and

(C 1 -C 6 )alkylthio;

R 2 is H,

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl and halo, or

(C 1 -C 3 )haloalkyl;

X is CO 2 R 8 ;

and

R, R 3 , R 4 , R 8 , and n are as defined in claim 1 .

9. The compound of claim 1 , wherein

R 1 is H,

(C 1 -C 6 )alkyl optionally substituted with one substituent selected from the group consisting of (C 1 -C 4 )alkoxy, phenyl optionally substituted with halo, and [tri(C 1 -C 4 )alkyl]silyl,

(C 3 -C 6 )alkenyl,

(C 3 -C 6 )alkynyl,

(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl, CF 3 , and halo, or

(C 1 -C 3 )haloalkyl;

R 2 is H,

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl and halo, or

(C 1 -C 3 )haloalkyl;

X is CO 2 R 8 ;

and

R, R 3 , R 4 , R 8 , and n are as defined in claim 1 .

10. The compound of claim 1 , wherein

R 1 is H,

(C 1 -C 6 )alkyl optionally substituted with one substituent selected from the group consisting of (C 1 -C 4 )alkoxy, phenyl optionally substituted with halo, and [tri(C 1 -C 4 )alkyl]silyl,

(C 3 -C 6 )alkenyl,

(C 3 -C 6 )alkynyl,

(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl, CF 3 , and halo, or

(C 1 -C 3 )haloalkyl;

R 2 is

phenyl optionally substituted with up to four substituents selected from the group consisting of

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

hydroxy,

NR 8 R 8 ,

cyano,

(C 1 -C 6 )alkylthio,

halo,

CO 2 R 8 ,

(C 1 -C 3 )haloalkoxy,

(C 1 -C 4 )acyl, and

benzoyl;

X is CO 2 R 8 ;

and

R, R 3 , R 4 , R 8 , and n are as defined in claim 1 .

11. The compound of claim 1 , wherein

R is H;

R 1 is H,

(C 1 -C 6 )alkyl optionally substituted with one substituent selected from the group consisting of (C 1 -C 4 )alkoxy, phenyl optionally substituted with halo, and [tri(C 1 -C 4 )alkyl]silyl,

(C 3 -C 6 )cycloalkyl optionally substituted with up to two substituents selected from the group consisting of (C 1 -C 3 )alkyl, CF 3 , and halo,

(C 1 -C 3 )haloalkyl, or

phenyl optionally substituted with up to four substituents selected from the group consisting of

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

NR 8 R 8 ,

cyano, and

(C 1 -C 6 )alkylthio;

R 2 is H,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

phenyl optionally substituted with up to four substituents selected from the group consisting of

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

hydroxy,

NR 8 R 8 ,

cyano,

(C 1 -C 6 )alkylthio,

halo,

CO 2 R 8 ,

(C 1 -C 3 )haloalkoxy,

(C 1 -C 4 )acyl, and

benzoyl;

R 3 is (C 1 -C 6 )alkyl,

(C 3 -C 6 )cycloalkyl, or

phenyl optionally substituted with up to four substituents selected from the group consisting of

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

halo,

(C 1 -C 3 )haloalkyl,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkoxy

NR 8 R 8 ,

cyano,

(C 1 -C 6 )alkylthio, and

SO 2 (C 1 -C 3 )alkyl;

R 4 is (C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

halo,

phenyl optionally substituted with up to four substituents selected from the group consisting of

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

NR 8 R 8 ,

cyano, and

(C 1 -C 6 )alkylthio;

n=0, 1, 2, or 3;

X is CO 2 R 8 ; and

R 8 is H,

(C 1 -C 6 )alkyl,

benzyl optionally substituted on the aryl ring with up to four substituents selected from the group consisting of

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 3 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

cyano, and

(C 1 -C 6 )alkylthio, or

phenyl optionally substituted with up to four substituents selected from the group consisting of

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

halo,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

cyano, and

(C 1 -C 6 )alkylthio.

12. The compound of claim 1 , wherein

R is H;

R 1 is H,

(C 1 -C 6 )alkyl optionally substituted with one substituent selected from the group consisting of (C 1 -C 4 )alkoxy, phenyl optionally substituted with halo, and [tri(C 1 -C 4 )alkyl]silyl, or

phenyl optionally substituted with up to four substituents selected from the group consisting of

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

NR 8 R 8 ,

cyano, and

(C 1 -C 6 )alkylthio;

R 2 is H,

halo, or

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy;

R 3 is (C 1 -C 6 )alkyl,

or

phenyl optionally substituted with up to four substituents selected from the group consisting of

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

halo,

(C 1 -C 3 )haloalkyl,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkoxy

NR 8 R 8 ,

cyano,

(C 1 -C 6 )alkylthio, and

SO 2 (C 1 -C 3 )alkyl;

R 4 is (C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

(C 1 -C 6 )alkylthio,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

halo;

n=0, 1, 2, or 3;

X is CONR 5 R 6 ;

R 5 is H,

(C 1 -C 6 )alkyl,

(C 2 -C 6 )alkyl substituted with OR 6 ,

benzyl optionally substituted on the aryl ring with up to four substituents selected from the group consisting of

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

NR 8 R 8 ,

cyano, and

(C 1 -C 6 )alkylthio,

phenyl optionally substituted with up to four substituents selected from the group consisting of

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

halo,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

NR 8 R 8 ,

cyano, and

(C 1 -C 6 )alkylthio,

or

SO 2 -phenyl said phenyl optionally substituted with up to four substituents selected from the group consisting of

halo

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

NR 8 R 8 ,

cyano, and

(C 1 -C 6 )alkylthio;

R 6 is H or (C 1 -C 6 )alkyl;

and

R 8 is H,

(C 1 -C 6 )alkyl,

benzyl optionally substituted on the aryl ring with up to four substituents selected from the group consisting of

halo,

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

(C 1 -C 3 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

cyano, and

(C 1 -C 6 )alkylthio,

or

phenyl optionally substituted with up to four substituents selected from the group consisting of

(C 1 -C 6 )alkyl optionally substituted with one (C 1 -C 4 )alkoxy,

halo,

(C 1 -C 6 )alkoxy,

(C 1 -C 3 )haloalkyl,

(C 1 -C 3 )haloalkoxy,

cyano, and

(C 1 -C 6 )alkylthio.

13. The compound of claim 1 selected from the group consisting of

2-[(3-tert-butyl-1-methyl-1H-pyrazol-5-yl)amino]-5-methoxybenzoic acid;

2-{[3-methyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzamide;

2-{[3-(4-fluorophenyl)-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid;

2-{[3-tert-butyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid;

2-{[3-tert-butyl-1-(2-methoxyphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid;

2-[(1,3-diphenyl-1H-pyrazol-5-yl)amino]-5-methoxybenzoic acid;

2-fluoro-6-{[3-(4-fluorophenyl)-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid;

2-fluoro-6-{[1-(2-methylphenyl)-3-(4-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid;

2-{[3-tert-butyl-1-(5-fluoro-2-methylphenyl)-1H-pyrazol-5-yl]amino}-6-fluorobenzoic acid;

2-({3-tert-butyl-1-[2-(methylthio)phenyl]-1H-pyrazol-5-yl}amino)-5-methoxybenzoic acid;

2-{[3-tert-butyl-1-(2-ethoxyphenyl)-1H-pyrazol-5-yl]amino}benzoic acid;

2-{[3-tert-butyl-1-(2-ethoxyphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid;

2-{[3-(3-methoxyphenyl)-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid;

5-methoxy-2-{[3-(3-methoxyphenyl)-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid;

2-{[3-(3-methoxyphenyl)-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-5-methylbenzoic acid;

2-{[3-tert-butyl-1-(2-methoxyphenyl)-4-methyl-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid;

2-[(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)amino]-5-methoxybenzoic acid;

2-{[3-tert-butyl-1-(5-fluoro-2-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid;

2-{[3-tert-butyl-1-(2,6-dimethylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid;

2-{[3-tert-butyl-1-(2-methoxy-5-methylphenyl)-1H-pyrazol-5-yl]amino}benzoic acid;

2-{[3-tert-butyl-1-(2,3-dimethylphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid;

2-{[3-tert-butyl-1-(2-methoxy-6-methylphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid;

2-{[3-tert-butyl-1-(2,6-dimethylphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid;

2-{[1-(2,6-dimethylphenyl)-3-(1-methylcyclopropyl)-1H-pyrazol-5-yl]amino}benzoic acid;

5) 2-{[1-(2,6-dimethylphenyl)-3-(3,3,3-trifluoropropyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid;

5-methoxy-2-{[3-methyl-1-(2-methylphenyl)-4-phenyl-1H-pyrazol-5-yl]amino}benzoic acid;

5-methoxy-2-{[1-(2-methylphenyl)-4-pyridin-4-yl-3-(trifluoromethyl)-1H-pyrazol-5-yl]amino}benzoic acid;

5-methoxy-2-{[4-(4-methoxyphenyl)-1-(2-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl]amino}benzoic acid;

2-{[4-(2-fluorophenyl)-3-methyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid;

5-methoxy-2-{[1-(2-methoxyphenyl)-3-methyl-4-phenyl-1H-pyrazol-5-yl]amino}benzoic acid; and

2-{[4-(2,4-dimethoxyphenyl)-3-methyl-1-(2-methylphenyl)-1H-pyrazol-5-yl]amino}-5-methoxybenzoic acid.

14. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, in combination with a pharmaceutically acceptable carrier.

15. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable carrier and one or more pharmaceutical agents.

16. The pharmaceutical composition of claim 15 , wherein said pharmaceutical agent is selected from the group consisting of PPAR agonists, sulfonylurea drugs, non-sulfonylurea secretagogues, α-glucosidase inhibitors, insulin sensitizers, insulin secretagogues, hepatic glucose output lowering compounds, insulin, anti-obesity agents, HMG CoA reductase inhibitors, nicotinic acid, bile acid sequestrants, fibric acid derivatives, and anti-hypertensive agents.

17. A composition comprising an effective amount of a compound of claim 1 , or a salt thereof, in combination with an inert carrier.

18. A method of treating diabetes comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .

19. The method of claim 18 , wherein said diabetes is selected from the group consisting of type 1 diabetes, type 2 diabetes, maturity-onset diabetes of the young, latent autoimmune diabetes adult, and gestational diabetes.

20. A method of treating Syndrome X comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .

21. A method of treating diabetes-related disorders comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .

22. The method of claim 21 , wherein said diabetes-related disorder is selected from the group consisting of hyperglycemia, hyperinsulinemia, impaired glucose tolerance, impaired fasting glucose, dyslipidemia, hypertriglyceridemia, and insulin resistance.

23. A method of treating obesity comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .

24. A method of treating cardiovascular diseases comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .

25. A method of treating diabetes comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 in combination with one or more pharmaceutical agents.

26. The method of claim 25 , wherein said pharmaceutical agent is selected from the group consisting of PPAR agonists, sulfonylurea drugs, non-sulfonylurea secretagogues, α-glucosidase inhibitors, insulin sensitizers, insulin secretagogues, hepatic glucose output lowering compounds, insulin, and anti-obesity agents.

27. The method of claim 25 , wherein said diabetes is selected from the group consisting of type 1 diabetes, type 2 diabetes, maturity-onset diabetes of the young, latent autoimmune diabetes adult, and gestational diabetes.

28. A method of treating Syndrome X comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 in combination with one or more pharmaceutical agents.

29. The method of claim 28 , wherein said pharmaceutical agent is selected from the group consisting of PPAR agonists, sulfonylurea drugs, non-sulfonylurea secretagogues, α-glucosidase inhibitors, insulin sensitizers, insulin secretagogues, hepatic glucose output lowering compounds, insulin, and anti-obesity agents.

30. A method of treating diabetes-related disorders comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 in combination with one or more pharmaceutical agents.

31. The method of claim 30 , wherein said diabetes-related disorder is selected from the group consisting of hyperglycemia, hyperinsulinemia, impaired glucose tolerance, impaired fasting glucose, dyslipidemia, hypertriglyceridemia, and insulin resistance.

32. The method of claim 30 , wherein said pharmaceutical agent is selected from the group consisting of PPAR agonists, sulfonylurea drugs, non-sulfonylurea secretagogues, α-glucosidase inhibitors, insulin sensitizers, insulin secretagogues, hepatic glucose output lowering compounds, insulin, and anti-obesity agents.

33. A method of treating diabetes, Syndrome X, or diabetes-related disorders comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 in combination with one or more agents selected from the group consisting of HMG CoA reductase inhibitors, nicotinic acid, bile acid sequestrants, fibric acid derivatives, and anti-hypertensive agents.

34. The method of claim 33 , wherein said diabetes-related disorder is selected from the group consisting of hyperglycemia, hyperinsulinemia, impaired glucose tolerance, impaired fasting glucose, dyslipidemia, hypertriglyceridemia, and insulin resistance.

35. The method of any one of claims 25 to 34 , wherein the compound of claim 1 and one or more pharmaceutical agents are administered as a single pharmaceutical dosage formulation.

36. A method of treating or preventing secondary causes of diabetes comprising the step of administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .

37. The method of claim 36 , wherein said secondary cause is selected from the group consisting of glucocorticoid excess, growth hormone excess, pheochromocytoma, and drug-induced diabetes.

38. A method of treating or preventing secondary causes of diabetes comprising the step of administering a subject in need thereof a therapeutically effective amount of a compound of claim 1 in combination with one or more pharmaceutical agents.

39. The method of claim 38 , wherein said pharmaceutical agent is selected from the group consisting of PPAR agonists, sulfonylurea drugs, non-sulfonylurea secretagogues, α-glucosidase inhibitors, insulin sensitizers, insulin secretagogues, hepatic glucose output lowering compounds, insulin, and anti-obesity agents.

40. A method of stimulating insulin secretion in a subject in need thereof by administering to said subject a compound of claim 1 .