Bis-heteroaryl derivatives as modulators of protein aggregation

1. A compound of Formula (I):

wherein

B is a 9- or 10-membered heteroaryl, or a 5- or 6-membered heterocycloalkyl, each unsubstituted or substituted with —(R 1 ) m ;

wherein m is 0, 1, or 2; and

each R 1 is independently C 1-4 alkyl (optionally substituted with one or more halogen or —O—C 1-4 alkyl groups), halogen, —OH, or —O—C 1-4 alkyl,

R 2 is H, C 1-5 alkyl (unsubstituted or substituted with one or more halo substituents), —OC 1-4 alkyl, or —S—C 1-4 alkyl, or an aryl, monocyclic cycloalkyl, or C 1-4 alkyl-(monocyclic cycloalkyl) group, wherein each aryl or cycloalkyl is unsubstituted or substituted with halo, C 1-4 alkyl, or halo-C 1-4 alkyl;

R 3 is H or C 1-4 alkyl;

A is a 5-membered heteroaryl ring; and

Ar is a phenyl or a 5 or 6-membered aromatic heterocycle, optionally substituted with (R 4 ) n ,

wherein n is 0, 1, 2, or 3; each R 4 is independently C 1-4 alkyl (optionally substituted with one or more halogen or OC 1-4 alkyl groups), halo, —OH, —CN, CF 3 , CHF 2 , CH 2 F, C 1-4 alkyl, C 1-4 branched alkyl or —OC 1-4 alkyl,

or a pharmaceutically acceptable salt thereof;

provided the compound of formula (I) is not any one of the group consisting of:

and pharmaceutically acceptable salts of any of the foregoing.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein m is 0.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein B is optionally substituted indole, benzofuran, benzothiophene, indazole, benzimidazole, benzoxazole, benzisoxazole, imidazopyridine, or pyrrolopyridine.

4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein B is optionally substituted indole.

5. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is a methyl, ethyl, propyl, tert-butyl or n-butyl, pentyl or hexyl group.

6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 2 is n-butyl.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein A is pyrrole, furan, thiophene, pyrazole, imidazole, oxazole, isoxazole, thiazole, triazole, oxadiazole, thiadiazole, or tetrazole.

8. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein A is a thiazole.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ar is a phenyl, pyridine, pyrimidine, pyridazine, pyrazine, pyrazole, imidazole, or triazole, each optionally substituted with (R 4 ) n , wherein each R 4 is independently C l-4 alkyl (optionally substituted with one or more halogen or OC 1-4 alkyl groups), halogen, —OH, —CN, CF 3 , CHF 2 , CH 2 F, C 1-4 alkyl, C 1-4 branched alkyl, or —OC 1-4 alkyl.

10. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein —(R 4 ) n is a C l-4 alkyl.

11. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Ar is a pyridine, pyrimidine, pyridazine, pyrazine, or pyrazole.

12. A compound of claim 1 , selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

13. A pharmaceutical composition comprising at least one compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

14. A method of treating Parkinson's Disease, comprising administering to a subject in need of such treatment an effective amount of at least one compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

15. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein B is an optionally substituted 3-indole.