Compounds for prevention or treatment of neurodegenerative disorders

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is cyclopropyl, cyclobutyl, 3- or 4-membered heterocyclyl, or —CF 3 , wherein R 1 is optionally substituted with one or more groups selected from the group consisting of halo, alkyl, hydroxyalkyl, haloalkyl, and monoalkylaminoalkyl,

R 2 and R 3 are independently —H, halo, C 1 -C 3 alkyl, alkoxy, —CF 3 , or —OCF 3 ,

R 4 , R 5 , R 6 and R 7 are independently —H, halo, C 1 -C 3 alkyl, alkoxy, aryl, heteroaryl, cycloalkyl, heterocyclyl, heteroalkyl, amino, —SMe, or —CN, wherein R 4 , R 5 , R 6 and R 7 are optionally substituted with one or more groups selected from the group consisting of halo, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, trimethylsilylethoxymethyl, —NO 2 , —NR a R b , —NR a C(═O)R b , —NR a C(═O)NR a R b , —NR a C(═O)OR b , —OR a , —CN, —C(═O)R a , —C(═O)OR a , —C(═O)NR a R b , —OC(═O)R a , —OC(═O)OR a , and —OC(═O)NR a R b , and

R a and R b are independently —H, halo, amino, alkyl, or haloalkyl.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, which is a compound of Formula (II):

wherein R 8 is selected from the group consisting of H, halo, C 1 -C 3 alkyl, C 1 -C 3 hydroxyalkyl, and C 1 -C 3 haloalkyl.

3. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein

R 2 and R 3 are —H;

R 4 , R 5 , R 6 and R 7 are independently —H, halo, C 1 -C 3 alkyl, alkoxy, aryl, heteroaryl, cycloalkyl, heterocyclyl, heteroalkyl, amino, —SMe, or —CN, wherein R 4 , R 5 , R 6 and R 7 are optionally substituted with one or more groups selected from the group consisting of halo, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, trimethylsilylethoxymethyl, —NO 2 , —NR a R b , —NR a C(═O)R b , —NR a C(═O)NR a R b , —NR a C(═O)OR b , —OR a , —CN, —C(═O)R a , —C(═O)OR a , —C(═O)NR a R b , —OC(═O)R a , —OC(═O)OR a , and —OC(═O)NR a R b ; and

R a and R b are independently —H, halo, amino, alkyl, or haloalkyl.

4. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

N-(5-(4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide;

(1R,2R)-2-fluoro-N-(5-(4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl) cyclopropane-1-carboxamide;

(1R,2S)-2-fluoro-N-(5-(4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl) cyclopropane-1-carboxamide;

(1S,2R)-2-fluoro-N-(5-(4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl) cyclopropane-1-carboxamide;

N-(5-(4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)cyclopropanecarboxamide;

(1S,2R)—N-(5-(4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1R,2S)—N-(5-(4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; and

(1R,2R)—N-(5-(4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide.

5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, which is a compound of Formula (III):

wherein R 8 is selected from the group consisting of —H, halo, C 1 -C 3 alkyl, C 1 -C 3 hydroxyalkyl, and C 1 -C 3 haloalkyl.

6. The compound of claim 5 or a pharmaceutically acceptable salt thereof, wherein

R 2 and R 3 are —H;

R 4 , R 5 , R 6 and R 7 are independently —H, halo, C 1 -C 3 alkyl, alkoxy, aryl, heteroaryl, cycloalkyl, heterocyclyl, heteroalkyl, amino, —SMe, or —CN, wherein R 4 , R 5 , R 6 and R 7 are optionally substituted with one or more groups selected from the group consisting of halo, hydroxyl, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyalkyl, trimethylsilylethoxymethyl, —NO 2 , —NR a R b , —NR a C(═O)R b , —NR a C(═O)NR a R b , —NR a C(═O)OR b , —OR a , —CN, —C(═O)R a , —C(═O)OR a , —C(═O)NR a R b , —OC(═O)R a , —OC(═O)OR a , and —OC(═O)NR a R b ;

R a and R b are independently —H, halo, amino, alkyl, or haloalkyl.

7. The compound of claim 5 or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

(1S,2S)—N-(5-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)—N-(5-(4-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(5-(6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl) cyclopropane-1-carboxamide;

(1S,2S)—N-(5-(6-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(5-(4-fluoro-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl) cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(5-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl) cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(5-(3-fluoro-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl) cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(5-(2-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl) cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(5-(4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl) cyclopropane-1-carboxamide;

(1S,2S)—N-(5-(4-amino-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)—N-(5-(3-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(5-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl) cyclopropane-1-carboxamide;

(1S,2S)—N-(5-(4-ethyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(5-(4-(methylthio)-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl) cyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(5-(4-isopropyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl) cyclopropane-1-carboxamide;

(1S,2S)—N-(5-(4-cyclopropyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)—N-(5-(4-cyano-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)—N-(5-(2-chloro-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)-2-fluoro-N-(5-(3-fluoro-4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl) cyclopropane-1-carboxamide;

(1S,2S)—N-(5-(3-chloro-4-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide;

(1S,2S)—N-(5-(3,4-dichloro-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide; and

(1S,2S)—N-(5-(4-chloro-3-fluoro-1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[1,5-a]pyridin-2-yl)-2-fluorocyclopropane-1-carboxamide.

8. The compound of claim 1 , wherein the salt is hydrochloric acid salt, tartaric acid salt, phosphoric acid salt, or maleic acid salt.

9. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

10. The pharmaceutical composition of claim 9 , further comprising one or more active ingredients that are useful to treat a neurodegenerative disease.

11. A method for treating an inflammatory and autoimmune disease in a subject, comprising:

administering to the subject in need thereof a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.

12. The method of claim 11 , wherein the inflammatory and autoimmune is a neuroinflammation disease.

13. The method of claim 11 , wherein the neuroinflammation disease is α-synucleinopathy, Parkinson's disease, dementia with Lewy body, multiple system atrophy (MSA), Alzheimer's disease, or amyotrophic lateral sclerosis (ALS).

14. The method of claim 11 , wherein the subject is a human.