Bicyclic agonists of GPR131 and uses thereof

1. A compound of formula (I)

or a derivative thereof, wherein

A is an optionally substituted aryl or heteroaryl;

D 1 and D 2 are each independently C or N; and D 3 , D 4 , and D 5 are each independently CR 2 , N, NR 8 , or O, wherein D 1 , D 2 , D 3 , D 4 , and D 5 together form Het 2 , which is an optionally substituted 5-membered heteroaryl;

E is alkyl, aryl, arylalkyl, cycloalkyl, heteroalkyl, heteroaryl, or heterocycloalkyl, each of which may be optionally substituted,

is selected from the group consisting of

and

R 2 is independently H, alkoxy, optionally substituted C 1-6 alkyl, amido, amino, cyano, halo, hydroxyl, sulfonyl, or sulfonamido; and

R 8 is H or optionally substituted C 1-6 alkyl.

2. The compound of claim 1 , wherein A is an optionally substituted phenyl or heteroaryl.

3. The compound of claim 2 , wherein A is phenyl optionally substituted with one or more substituents selected from the group consisting of alkoxy, amido, amino, an optionally substituted C 1-6 alkyl, carboxylate, cyano, halo, and hydroxyl.

4. The compound of claim 1 , wherein Het 2 is selected from the group consisting of imidazole, triazole and tetrazole.

5. The compound of claim 1 , wherein D 2 is carbon.

6. The compound of claim 1 , wherein E is an optionally substituted aryl or heteroaryl.

7. A compound represented by Formula (Ib2)

or a derivative thereof, wherein

A is an optionally substituted aryl or heteroaryl;

D 4 and D 5 are each independently CR 2 , or N, wherein D 4 and D 5 together with the two nitrogen attached thereto Het 2 , which is an optionally substituted 5-membered heteroaryl;

E is aryl, cycloalkyl, heteroalkyl, heteroaryl, or heterocycloalkyl, each of which may be optionally substituted, or E is an unsubstituted alkyl; and

R 2 is independently H, alkoxy, optionally substituted C 1-6 alkyl, amido, amino, cyano, halo, hydroxyl, sulfonyl, or sulfonamido.

8. A compound represented by Formula (Ib3)

or a derivative thereof, wherein

A is an optionally substituted aryl or heteroaryl;

D 3 and D 5 are each independently CR 2 or N, wherein D 3 and D 5 together with the two nitrogen attached thereto Het 2 , which is an optionally substituted 5-membered heteroaryl;

E is aryl, cycloalkyl, heteroalkyl, heteroaryl, or heterocycloalkyl, each of which may be optionally substituted, or E is an unsubstituted alkyl; and

R 2 is independently H, alkoxy, optionally substituted C 1-6 alkyl, amido, amino, cyano, halo, hydroxyl, sulfonyl, or sulfonamido.

9. A compound selected from the group consisting of:

2-(2-Chlorophenyl)-3-(1-(4-chlorophenyl)-1H-tetrazol-5-yl)imidazo[1,2-a]pyridine;

2-(2-Chlorophenyl)-3-(4-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

3-(4-Cyclohexyl-4H-1,2,4-triazol-3-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine;

2-(2-Chlorophenyl)-3-(1-(4-chlorophenyl)-1H-1,2,4-triazol-5-yl)imidazo[1,2-a]pyridine;

3-(1-(4-Chlorophenyl)-3-methyl-1H-1,2,4-triazol-5-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine;

3-(4-(4-Chlorophenyl)-5-methyl-4H-1,2,4-triazol-3-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine;

3-(1-(4-Chlorophenyl)-1H-imidazol-2-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine;

3-(1-(4-Chlorophenyl)-1H-imidazol-5-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine;

2-(2,5-Dichlorophenyl)-3-(4-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

2-(2,5-Dichlorophenyl)-3-(4-isopropyl-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

4-(3-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)-N,N-dimethylaniline;

4-(4-(3-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)phenyl)morpholine;

2-(2,5-Dichlorophenyl)-3-(4-(4-(methylsulfonyl)phenyl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

2-(2,5-Dichlorophenyl)-3-(4-(4-(trifluoromethyl)phenyl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

5-(3-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)-1H-indazole;

4-(3-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)benzonitrile;

6-(3-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)-1H-indazole;

6-(3-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)-1-methyl-1H-benzo[d]imidazole;

5-(3-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)benzo[d]thiazole;

5-(3-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)-1-methyl-1H-indazole;

6-(3-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)-1-methyl-1H-indazole;

5-(3-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)-1-methyl-1H-benzo[d]imidazole;

6-(3-(2-(2-Chlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)-1H-indazole;

3-(4-(1H-Indazol-6-yl)-4H-1,2,4-triazol-3-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-b]pyridazine;

3-(4-(4-Chlorophenyl)-4H-1,2,4-triazol-3-yl)-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine;

4-(4-Chlorophenyl)-3-(2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-1H-1,2,4-triazol-5 (4H)-one;

4-(4-Chlorophenyl)-3-(2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-1H-1,2,4-triazole-5 (4H)-thione;

3-(4-(4-Chlorophenyl)-5-methoxy-4H-1,2,4-triazol-3-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine;

3-(4-(4-Chlorophenyl)-5-(methylthio)-4H-1,2,4-triazol-3-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine;

2-(2,5-Dichlorophenyl)-3-(4-(4-ethylphenyl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

2-(2,5-Dichlorophenyl)-3-(4-(4-isopropylphenyl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

3-(4-([1,1′-Biphenyl]-4-yl)-4H-1,2,4-triazol-3-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine;

Ethyl 4-(3-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine-3-yl)-4H-1,2,4-triazol-4-yl)benzoate;

2-(2,5-Dichlorophenyl)-3-(4-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

2-(2,5-Dichlorophenyl)-3-(4-(2-fluorophenyl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

2-(2,5-Dichlorophenyl)-3-(4-(3-fluorophenyl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

2-(2,5-Dichlorophenyl)-3-(4-(1-methyl-1H-indol-5-yl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

2-(2,5-Dichlorophenyl)-3-(4-(4-(3-(trifluoromethyl)-1H-pyrazol-1-yl)phenyl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

4-(3-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridine-3-yl)-4H-1,2,4-triazol-4-yl)-3,5-dimethylisoxazole;

N-(4-(3-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)phenyl)-N-methylacetamide;

2-(2,5-Dichlorophenyl)-3-(4-(6-methylpyridin-3-yl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

6-(3-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)quinoline;

N-(2-Chloro-4-(3-(2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)phenyl)acetamide;

3-(4-(4-Chlorobenzyl)-4H-1,2,4-triazol-3-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine;

4-(3-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)-1H-indazole;

4-(3-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)-1-methyl-1H-indazole;

2-(2,5-Dichlorophenyl)-3-(4-(4-(4-methylpiperazin-1-yl)phenyl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

4-(3-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridine-3-yl)-4H-1,2,4-triazol-4-yl)-N,N-dimethylbenzamide;

4-(3-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridine-3-yl)-4H-1,2,4-triazol-4-yl)benzoic acid;

2-(2-Chloro-5-fluorophenyl)-3-(1-(4-chlorophenyl)-1H-tetrazol-5-yl)imidazo[1,2-a]pyrimidine;

2-(2-Chloro-5-fluorophenyl)-3-(1-(4-chlorophenyl)-1H-tetrazol-5-yl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrimidine;

5-(1-(4-Chlorophenyl)-1H-tetrazol-5-yl)-6-(2,5-dichlorophenyl)imidazo[2,1-b]oxazole;

3-(1-(4-Chlorophenyl)-1H-tetrazol-5-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine;

3-(4-(4-Chlorophenyl)-4H-1,2,4-triazol-3-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine;

3-(1-(4-Chlorophenyl)-1H-1,2,4-triazol-5-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine;

3-(1-(4-Chlorophenyl)-1H-tetrazol-5-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-b]pyridazine;

3-(1-(4-Chlorophenyl)-1H-tetrazol-5-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyrazine;

2-(2-Chlorophenyl)-3-(1-(4-chlorophenyl)-1H-imidazol-2-yl)imidazo[1,2-a]pyridine;

3-(1-(4-Chlorophenyl)-1H-tetrazol-5-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyrimidine;

3-(1-(4-Chlorophenyl)-1H-tetrazol-5-yl)-2-(2,5-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine;

3-(1-(4-Chlorophenyl)-1H-imidazol-2-yl)-2-(2,5-dichlorophenyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyridine;

3-(1-(4-Chlorophenyl)-1H-imidazol-2-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-b]pyridazine;

2-(2,5-Dichlorophenyl)-3-(1-(4-(trifluoromethyl)phenyl)-1H-tetrazol-5-yl)imidazo[1,2-a]pyridine;

2-(2,5-Dichlorophenyl)-3-(1-(4-(trifluoromethyl)phenyl)-1H-tetrazol-5-yl)imidazo[1,2-b]pyridazine;

2-(2, 5-Dichlorophenyl)-3-(1-(4-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)imidazo[1,2-a]pyridine;

2-(2, 5-Dichlorophenyl)-3-(1-(4-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)imidazo[1,2-b]pyridazine;

4-(5-(2-(2, 5-Dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-1H-tetrazol-1-yl)benzonitrile;

4-(2-(2-(2,5-Dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-1H-imidazol-1-yl)benzonitrile;

6-(3-(2-(3-Chlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)-1H-indazole;

3-(4-(4-chloro-3-(trifluoromethyl)phenyl)-4H-1,2,4-triazol-3-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine;

2-(2, 5-dichlorophenyl)-3-(4-(1-methyl-1H-indol-6-yl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

6-chloro-3-(3-(2-(2, 5-dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)-1-methyl-1H-indazole;

2-(2, 5-dichlorophenyl)-3-(4-(5-methylpyridin-2-yl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

2-(2, 5-dichlorophenyl)-3-(4-(pyrimidin-5-yl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

2-(2, 5-dichlorophenyl)-3-(4-(4-(pyrrolidin-1-yl)phenyl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

4-(2-(2-(2,5-dichlorophenyl)imidazo[1,2-b]pyridazin-3-yl)-1H-imidazol-1-yl)benzonitrile;

3-(5-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl)-2-(2, 5-dichlorophenyl)imidazo[1,2-a]pyridine;

2-(2, 5-dichlorophenyl)-3-(4-(1-methylindolin-5-yl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

5-(3-(2-(2, 5-dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)-N,N-dimethylpyridin-2-amine;

5-(3-(2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)picolinonitrile;

3-(4-(benzofuran-5-yl)-4H-1,2,4-triazol-3-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine;

2-(2,5-dichlorophenyl)-3-(4-(2,3-dihydrobenzofuran-5-yl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

4-(3-(2-(4-chlorophenyl)pyrazolo[1,5-a]pyridin-3-yl)-4H-1,2,4-triazol-4-yl)benzonitrile;

3-(3-(4-chlorophenyl)-4H-1,2,4-triazol-4-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine;

4-(3-(2-(4-chlorophenyl)pyrazolo[1,5-b]pyridazin-3-yl)-4H-1,2,4-triazol-4-yl)benzonitrile;

3-(4-(7-chloro-2-methylbenzofuran-5-yl)-4H-1,2,4-triazol-3-yl)-2-(2,5-dichlorophenyl)imidazo[1,2-a]pyridine;

2-(4-chlorophenyl)-3-(4-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl)pyrazolo[1,5-b]pyridazine;

2-(2-chlorophenyl)-3-(4-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-b]pyridazine;

3-(4-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl)-2-(2-fluoro-5-methylphenyl)imidazo[1,2-a]pyridine;

4-(3-(2-(2-chlorophenyl)imidazo[1,2-b]pyridazin-3-yl)-4H-1,2,4-triazol-4-yl)benzonitrile;

3-(4-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl)-2-(2,5-dimethylphenyl)imidazo[1,2-a]pyridine;

2-(2,5-dichlorophenyl)-3-(4-(2-methylbenzofuran-5-yl)-4H-1,2,4-triazol-3-yl)imidazo[1,2-a]pyridine;

3-(4-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl)-2-(2,5-dichlorophenyl)-4,5,6,7-tetrahydro-2H-indazole;

4-(3-(2-(2,5-dichlorophenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl)-4H-1,2,4-triazol-4-yl)benzonitrile; and

4-(3-(2-(2,5-dichlorophenyl)pyrazolo[1,5-b]pyridazin-3-yl)-4H-1,2,4-triazol-4-yl)benzonitrile,

or a salt, racemate, or a tautomer thereof.

10. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

11. The compound of claim 1 , wherein the derivative is a pharmaceutically acceptable salt or a tautomer.

12. A pharmaceutical composition comprising a compound of claim 9 and a pharmaceutically acceptable carrier.

13. The compound of claim 1 , wherein

14. The compound of claim 1 , wherein

15. The compound of claim 1 , wherein

16. The compound of claim 1 , wherein

17. The compound of claim 1 , wherein

18. The compound of claim 1 , wherein

19. A pharmaceutical composition comprising a compound of claim 7 and a pharmaceutically acceptable carrier.

20. A pharmaceutical composition comprising a compound of claim 8 and a pharmaceutically acceptable carrier.