3-aryl-2H-pyrazolo[4,3-b]pyridine compounds and their use as AMPA receptor modulators

1. A compound of Formula (I):

wherein

R 1 is selected from the group consisting of: C 1-6 alkyl, C 1-6 haloalkyl, CH 2 CH 2 OCH 3 , C 3-8 cycloalkyl, CH 2 —C 3-8 cycloalkyl, phenyl and pyridyl;

R 2 is selected from the group consisting of: H, halo, and CH 3 ;

R 3 is C 1-6 haloalkyl;

is selected from the group consisting of: —CH═N—, —CH 2 —C(═O)—, —S—C(═O)—, and —NH—C(═O)—; and

R 5 is H or CHF 2 ; and

pharmaceutically acceptable salts, N-oxides, or solvates thereof.

2. The compound of claim 1 , wherein R 1 is C 1-6 alkyl, C 1-6 haloalkyl, CH 2 CH 2 OCH 3 , CH 2 cyclobutyl, cyclobutyl, cyclopentyl, phenyl, or pyridin-2-yl.

3. The compound of claim 1 , wherein R 2 is H, Cl or CH 3 .

4. The compound of claim 1 , wherein R 3 is CF 3 .

5. The compound of claim 1 , wherein R 3 is CF 2 H.

6. The compound of claim 1 , wherein

is —CH═N—.

7. The compound of claim 1 , wherein

is —CH 2 —C(═O)—.

8. The compound of claim 1 , wherein

is —NH—C(═O)—.

9. The compound of claim 1 , wherein

is —S—C(═O)—.

10. The compound of claim 1 , wherein R 5 is H.

11. The compound of claim 1 , wherein R 5 is CHF 2 .

12. The compound of claim 1 , and pharmaceutically acceptable salts, solvates, or N-oxides thereof, having the structure of Formula (IA):

wherein

R 1 is selected from the group consisting of: C 1-6 alkyl, C 1-6 haloalkyl, CH 2 CH 2 OCH 3 , C 3-8 cycloalkyl, CH 2 —C 3-8 cycloalkyl, phenyl and pyridyl; and

R 4 is selected from the group consisting of:

13. A compound selected from the group consisting of:

5-(2-Methyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one;

7-Methyl-5-(2-methyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridin-3-yl)indolin-2-one;

5-[2-(Difluoromethyl)-5-(trifluoromethyl)pyrazolo[4,3-b]pyridin-3-yl]-7-methyl-indolin-2-one;

5-(2-Ethyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one;

5-(2-Isopropyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one;

5-(2-(Cyclobutylmethyl)-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one;

5-(2-Cyclopentyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one;

2-Cyclopentyl-3-(7-methyl-1H-indazol-5-yl)-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridine;

5-(2-Phenyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridin-3-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one;

5-(2-Phenyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridin-3-yl)indolin-2-one;

3-(1H-Indazol-5-yl)-2-phenyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridine;

2-Cyclobutyl-3-(1H-indazol-5-yl)-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridine;

3-(1H-Indazol-5-yl)-2-(2-methoxyethyl)-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridine;

3-(1H-Indazol-5-yl)-2-(pyridin-2-yl)-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridine;

2-Methyl-3-(7-methyl-1H-indazol-5-yl)-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridine;

3-(7-Chloro-1H-indazol-5-yl)-2-methyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridine;

5-(2-Ethyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridin-3-yl)-7-methylindolin-2-one;

7-Chloro-5-(2-ethyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridin-3-yl)indolin-2-one;

2-Ethyl-3-(7-methyl-1H-indazol-5-yl)-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridine;

3-(7-Chloro-1H-indazol-5-yl)-2-ethyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridine;

5-(2-Isopropyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridin-3-yl)-7-methylindolin-2-one;

7-Chloro-5-(2-isopropyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridin-3-yl)indolin-2-one;

2-Isopropyl-3-(7-methyl-1H-indazol-5-yl)-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridine;

3-(7-Chloro-1H-indazol-5-yl)-2-isopropyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridine;

5-(2-Cyclobutyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridin-3-yl)-7-methylindolin-2-one;

7-Chloro-5-(2-cyclobutyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridin-3-yl)indolin-2-one;

2-Cyclobutyl-3-(7-methyl-1H-indazol-5-yl)-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridine;

3-(7-Chloro-1H-indazol-5-yl)-2-cyclobutyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridine;

7-Chloro-5-(2-(difluoromethyl)-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridin-3-yl)indolin-2-one;

2-(Difluoromethyl)-3-(7-methyl-1H-indazol-5-yl)-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridine;

3-(7-Chloro-1H-indazol-5-yl)-2-(difluoromethyl)-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridine;

5-(Difluoromethyl)-2-isopropyl-3-(7-methyl-1H-indazol-5-yl)-2H-pyrazolo[4,3-b]pyridine;

7-Chloro-5-(5-(difluoromethyl)-2-isopropyl-2H-pyrazolo[4,3-b]pyridin-3-yl)indolin-2-one;

7-(Difluoromethyl)-2-isopropyl-3-(7-methyl-1H-indazol-5-yl)pyrazolo[4,3-b]pyridine;

3-(7-Chloro-1H-indazol-5-yl)-2-isopropyl-pyrazolo[4,3-b]pyridine; and

5,7-Bis(difluoromethyl)-2-isopropyl-3-(7-methyl-1H-indazol-5-yl)pyrazolo[4,3-b]pyridine; and

pharmaceutically acceptable salts, N-oxides or solvates thereof.

14. A compound selected from the group consisting of:

6-(2-Isopropyl-5-(trifluoromethyl)-2H-pyrazolo[4,3-b]pyridin-3-yl)benzo[d]thiazol-2(3H)-one;

3-(7-Chloro-1H-indazol-5-yl)-5-(difluoromethyl)-2-isopropyl-2H-pyrazolo[4,3-b]pyridine;

5-(5-(Difluoromethyl)-2-isopropyl-2H-pyrazolo[4,3-b]pyridin-3-yl)-7-methylindolin-2-one; and

6-(5-(Difluoromethyl)-2-isopropyl-2H-pyrazolo[4,3-b]pyridin-3-yl)benzo[d]thiazol-2(3H)-one; and

pharmaceutically acceptable salts, N-oxides or solvates thereof.

15. A pharmaceutical composition comprising:

(A) an effective amount of at least one compound of Formula (I):

wherein

R 1 is selected from the group consisting of: C 1-6 alkyl, C 1-6 haloalkyl, CH 2 CH 2 OCH 3 , C 3-8 cycloalkyl, CH 2 —C 3-8 cycloalkyl, phenyl and pyridyl;

R 2 is selected from the group consisting of: H, halo, and CH 3 ;

R 3 is C 1-6 haloalkyl;

is selected from the group consisting of: —CH═N—, —CH 2 —C(═O)—, —S—C(═O)—, and —NH—C(═O)—; and

R 5 is H or CHF 2 ; and

pharmaceutically acceptable salts, N-oxides or solvates of compounds of Formula (I); and

(B) at least one pharmaceutically acceptable excipient.

16. A pharmaceutical composition comprising an effective amount of at least one compound of claim 13 and at least one pharmaceutically acceptable excipient.