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1. (WO2012103008) HISTONE DEACETYLASE INHIBITORS AND COMPOSITIONS AND METHODS OF USE THEREOF
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What is claimed:

1 . A compound of Formula I


or a pharmaceutically acceptable salt thereof wherein

R1 and R2 are independently chosen from optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, and optionally substituted heteroaryl;

R3 is chosen from -COOH, -C(O)NH(OH) and -N(OH)C(O)R4;

R3a is chosen from hydrogen and lower alkyl optionally substituted with halo; and

R4 is chosen from hydrogen and lower alkyl;

wherein if R1 and R2 are both phenyl and R3a is hydrogen, then R3 is -N(OH)C(O)H or -C(O)NH(OH).

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is chosen from compounds of Formula

II


3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is chosen from compounds of Formula

III


4. The compound of any one of claims 1 to 3, or a pharmaceutically

acceptable salt thereof, wherein R3a is hydrogen or methyl.

5. The compound of any one of claims 1 to 3, or a pharmaceutically

acceptable salt thereof, wherein R3a is -CF3.

6. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is chosen from compounds of Formula IV


7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound of Formula I is chosen from compounds of Formula V.


8. The compound of any one of claims 1 to 7, or a pharmaceutically

acceptable salt thereof, wherein R3 is chosen from -C(O)NH(OH) and - N(OH)C(O)R4.

9. The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein R3 is -C(O)NH(OH).

10. The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein R3 is -N(OH)C(O)R4 wherein R4 is hydrogen.

1 1 . The compound of claim 8, or a pharmaceutically acceptable salt thereof, wherein R3 is -N(OH)C(O)R4 wherein R4 is methyl.

12. The compound of any one of claims 1 to 1 1 , or a pharmaceutically

acceptable salt thereof, wherein R2 is chosen from cycloalkyl,

heterocycloalkyl, alkyl, aryl and heteroaryl, each of which is optionally substituted with one, two, or three groups independently chosen from -R21 , -OR22, halo, and -NR23SO2R21 , wherein

R21 is chosen from optionally substituted C1-C6 alkyl, optionally

substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocycloalkyl, and optionally substituted heteroaryl;

R22 is chosen from H, optionally substituted C1-C6 alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; and

R23 is chosen from hydrogen and optionally substituted C1-C4 alkyl.

13. The compound of claim 12, or a pharmaceutically acceptable salt thereof, wherein R2 is chosen from cyclohexyl, thiophen-2-yl, thiazol-5-yl, and phenyl, each of which is optionally substituted with one, two, or three groups independently chosen from -R21 , -OR22, and halo.

14. The compound of claim 13, or a pharmaceutically acceptable salt thereof, wherein R2 is thiophen-2-yl or phenyl, each of which is optionally

substituted with one, two, or three groups independently chosen from lower alkyl, lower alkoxy, trifluoromethyl, and halo.

15. The compound of claim 14, or a pharmaceutically acceptable salt thereof, wherein R2 is chosen from phenyl, 2-chlorophenyl, 2-fluorophenyl, 2- methylphenyl, 2-trifluoromethylphenyl, 3-fluorophenyl, 3-methylphenyl, 3- trifluoromethylphenyl, 4-fluorophenyl, 5-methylthiophen-2-yl, 3-fluoro-5- methylthiophen-2-yl, 5-methyl-3-(trifluoromethyl)thiophen-2-yl, and 5- (trifluoromethyl)thiophen-2-yl.

16. The compound of claim 15, or a pharmaceutically acceptable salt thereof, wherein R2 is chosen from phenyl, 2-fluorophenyl, 3-fluorophenyl, and 4- fluorophenyl.

17. The compound of claim 16, or a pharmaceutically acceptable salt thereof, wherein R2 is phenyl.

18. The compound of any one of claims 1 to 17, or a pharmaceutically

acceptable salt thereof, wherein R1 is chosen from alkyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl, each of which is optionally substituted with one, two, or three groups independently chosen from -R11 , -O R12, halo, -NR12 R13, -C(O)R12, -C(O)OR12, -C(O)N R12R13, -OC(O)R12,

-OC(O)O R11 , -OC(O)NR12R13, -NR13C(O) R12, -NR13C(O)OR11 ,

-NR13C(O)NR12R13, -S(O) R11 , -SO2R11 , -SO2NR12R13, and -NR13SO2R11 , wherein

R11 is chosen from optionally substituted C1-C6 alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkenyl, optionally substituted aryl, optionally substituted

heterocycloalkyl, optionally substituted heterocycloalkenyl, and optionally substituted heteroaryl;

R12 is chosen from H, optionally substituted C1-C6 alkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl; and

R1 3 is chosen from hydrogen and optionally substituted C1-C4 alkyl.

19. The compound of claim 18, or a pharmaceutically acceptable salt thereof, wherein R1 is phenyl optionally substituted with one, two, or three groups independently chosen from -R11 , -O R12, halo, -C(O) R12, -N R12R13, and -NR13SO2R11.

20. The compound of claim 19, or a pharmaceutically acceptable salt thereof, wherein R1 is phenyl optionally substituted with one, two or three groups independently selected from

halo,

lower alkyl,

aryl optionally substituted with one or two groups independently

chosen from lower alkyl, trifluoromethyl,cycloalkyl, phenyl, and benzyloxy,

heteroaryl optionally substituted with one or two groups independently chosen from lower alkyl, trifluoromethyl, cycloalkyl, and phenyl,

(cycloalkyl)sulfonamido, and

heterocycloalkyl optionally substituted with one or two groups

independently chosen from halo, lower alkyl, trifluoromethyl, cycloalkyl, heterocycloalkyl, and phenyl.

21 . The compound of claim 20, or a pharmaceutically acceptable salt thereof, wherein R1 is phenyl optionally substituted with one, two or three groups independently selected from halo, lower alkyl, oxazol-2-yl, oxazol-5-yl, pyrimidin-2-yl, pyrimidin-5-yl, pyridazin-3-yl, pyridazin-4-yl, 1 H-pyrazol-1 -yl, (cycloalkyl)sulfonamido, 1 H-imidazol-1 -yl, imidazol-2-yl, 1 ,2,3,6- tetrahydropyridin-4-yl, azetidin-1 -yl, pyrrolidin-1 -yl, 2-oxa-6- azaspiro[3.3]heptan-6-yl, phenyl, hexahydropyrrolo[1 ,2-a]pyrazin-2(1 H)-yl, piperidin-1 -yl, piperazin-1 -yl, and 6,7-dihydropyrazolo[1 ,5-a]pyrimidin-

4(5H)-yl, each of which is optionally substituted with one or two groups independently chosen from halo, lower alkyl, trifluoromethyl, phenyl, cycloalkyl, benzyl, benzyloxy, and pyrrolidin-1 -yl.

22. The compound of claim 21 , or a pharmaceutically acceptable salt thereof, wherein R1 is chosen from phenyl, 2-methylphenyl, 3-methylphenyl, 4- methylphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2- bromophenyl, 3-bromophenyl, 4-bromophenyl, 4-(1 -benzyl-1 ,2,3,6- tetrahydropyridin-4-yl)phenyl, 4-(pyrimidin-2-yl)phenyl, 4-(pyrimidin-5- yl)phenyl, 4-(5-methylpyrimidin-2-yl)phenyl,3-(5-fluoropyrimidin-2- yl)phenyl, 4-(5-chloropyrimidin-2-yl)phenyl, 4-(5-fluoropyrimidin-2- yl)phenyl, 4-(4-(trifluoromethyl)pyrimidin-2-yl)phenyl, 4-(5- trifluoromethylpyrimidin-2-yl)phenyl, 4-(5-cyclopropylpyrimidin-2-yl)phenyl, 4-(pyridazin-3-yl)phenyl, 4-(pyridazin-4-yl)phenyl, 4-(1 H-imidazol-1 - yl)phenyl, 4-(1 -methyl-1 H-imidazol-2-yl)phenyl, 4-(5-methyl-1 H-imidazol-2- yl)phenyl), 4-(1 H-pyrazol-1 -yl)phenyl, 4-(3-methyl-1 H-pyrazol-1 -yl)phenyl, 4-(3-(trifluoromethyl)-1 H-pyrazol-1 -yl)phenyl, 3-(oxazol-5-yl)phenyl, 4- (oxazol-2-yl)phenyl, 4-(oxazol-5-yl)phenyl, 4-(2-methyloxazol-5- yl)phenyl,4-(2-cyclopropyloxazol-5-yl)phenyl, 4-(2-phenyloxazol-5- yl)phenyl, 4-(cyclopropanesulfonamido)phenyl, 4-(3,3-dimethylazetidin-1 - yl)phenyl, 4-(3,3-difluoropyrrolidin-1 -yl)phenyl, 4-(2-oxa-6- azaspiro[3.3]heptan-6-yl)phenyl, 3'-(benzyloxy)biphenyl-4-yl, 3- (hexahydropyrrolo[1 ,2-a]pyrazin-2(1 H)-yl)phenyl, 3-(4-(pyrrolidin-1 - yl)piperidin-1 -yl)phenyl, 4-(4-methylpiperazin-1 -yl)phenyl, 4-(4- isopropylpiperazin-1 -yl)phenyl, and 3-(6,7-dihydropyrazolo[1 ,5-a]pyrimidin- 4(5H)-yl)phenyl.

23. The compound of claim 22, or a pharmaceutically acceptable salt thereof, wherein R1 is chosen from 4-(1 -benzyl-1 ,2,3,6-tetrahydropyridin-4- yl)phenyl, 4-(pyrimidin-2-yl)phenyl, 4-(5-methylpyrimidin-2-yl)phenyl, 4-(5- chloropyrimidin-2-yl)phenyl, 4-(5-fluoropyrimidin-2-yl)phenyl, 4-(4- (trifluoromethyl)pyrimidin-2-yl)phenyl, 4-(5-cyclopropylpyrimidin-2- yl)phenyl, 4-(pyridazin-3-yl)phenyl, 4-(pyridazin-4-yl)phenyl, 4-(5-methyl- 1 H-imidazol-2-yl)phenyl), 4-(5-(trifluoromethyl)-1 H-imidazol-2-yl)phenyl, 3- chloro-4-(5-methyl-1 H-imidazol-2-yl)phenyl, 3-fluoro-4-(5-methyl-1 H- imidazol-2-yl)phenyl, 4-(1 H-pyrazol-1 -yl)phenyl, 3-(oxazol-5-yl)phenyl, 4- (oxazol-2-yl)phenyl, 4-(oxazol-5-yl)phenyl, 4-(2-cyclopropyloxazol-5- yl)phenyl, 4-(4-isopropylpiperazin-1 -yl)phenyl, and 3-(6,7- dihydropyrazolo[1 ,5-a]pyhmidin-4(5H)-yl)phenyl.

24. The compound of claim 18, or a pharmaceutically acceptable salt thereof, wherein R1 is chosen from 1 ,2,3,4-tetrahydroquinolin-6-yl, 2,3,4,5- tetrahydrobenzo[f][1 ,4]oxazepin-7-yl, 1 ,2,3,4-tetrahydropyrrolo[1 ,2- a]pyrazin-7-yl, imidazo[1 ,2-a]pyridin-7-yl, imidazo[1 ,2-a]pyridin-3-yl, pyrrolo[1 ,2-a]pyrimidin-4-yl, 1 ,5-naphthyridin-4-yl, 2,3- dihydrobenzo[b][1 ,4]dioxin-6-yl, benzo[d][1 ,3]dioxol-5-yl, and 1 -oxo- isoindolin-5-yl, each of which is optionally substituted with one or two groups independently chosen from halo and lower alkyl optionally substituted with one, two, or three halo groups.

25. The compound of claim 18, or a pharmaceutically acceptable salt thereof, wherein R1 is heteroaryl optionally substituted with one, two, or three groups independently chosen from -R11 , -O R12, halo, and -NR13SO2R11.

26. The compound of claim 25, or a pharmaceutically acceptable salt thereof, wherein R1 is chosen from pyridin-3-yl, pyridin-4-yl, 1 H-pyrazol-4-yl, pyrimidin-5-yl, pyridazin-4-yl, benzo[d]isoxazol-3-yl, benzo[d]oxazol-6-yl, and thiazol-5-yl, each of which is optionally substituted with one, two, or three groups independently chosen from -R11 , -O R12, halo, and

-NR13SO2R11.

27. The compound of claim 26, or a pharmaceutically acceptable salt thereof, wherein R1 is chosen from pyridin-3-yl, pyridin-4-yl, 1 H-pyrazol-4-yl, pyrimidin-5-yl, pyridazin-4-yl, benzo[d]isoxazol-3-yl, benzo[d]oxazol-6-yl, and thiazol-5-yl, each of which is optionally substituted with one or two groups independently chosen from halo, lower alkyl, 2,2,2-

trifluoroethylamino, trifluoromethyl, 2,2,2-trifluoroethyl, cycloalkyl, cyclopropylmethyl, 1 H-pyrazol-1 -yl optionally substituted with lower alkyl, pyrimidin-2-yl optionally substituted with lower alkyl or halo, oxazol-5-yl optionally substituted with lower alkyl, piperazin-1 -yl optionally substituted with lower alkyl, piperidin-4-yl optionally substituted with 2,2,2- trifluoroethyl, and pyridin-2-yl optionally substituted with lower alkyl or trifluoromethyl.

28. The compound of claim 27, or a pharmaceutically acceptable salt thereof, wherein R1 is chosen from 2-cyclopropylpyridin-4-yl, 6- (trifluoromethyl)pyridin-3-yl, 2-(trifluoromethyl)pyridin-4-yl, 5- (trifluoromethyl)pyridin-3-yl, 2-(2,2,2-trifluoroethylamino)pyridin-4-yl, 6- (2,2,2-trifluoroethylamino)pyridin-3-yl, 6-(3-methyl-1 H-pyrazol-1 -yl)pyridin- 3-yl, 6-(5-methylpyrimidin-2-yl)pyridin-3-yl, 6-(2-methyloxazol-5-yl)pyridin- 3-yl, 6-(5-chloropyrimidin-2-yl)pyridin-3-y1, 6-(4-isopropylpiperazin-1 - yl)pyridin-3-yl, 2,6-dicyclopropylpyridin-4-yl, 6-(5-fluoropyrimidin-2- yl)pyridin-3-yl, 2-(5-chloropyrimidin-2-yl)-6-cyclopropylpyridin-4-yl, 1 - methyl-1 H-pyrazol-4-yl, 1 -(2,2,2-trifluoroethyl)-1 H-pyrazol-4-yl, 1 - (cyclopropylmethyl)-1 H-pyrazol-4-yl, 1 -cyclopropyl-1 H-pyrazol-4-yl, 1 ,3- dimethyl-1 H-pyrazol-4-yl, 1 -(1 -(2,2,2-trifluoroethyl)piperidin-4-yl)-1 H- pyrazol-4-yl, 1 -(5-(trifluoromethyl)pyridin-2-yl)-1 H-pyrazol-4-yl, 1 -(5- (trifluoromethyl)pyridin-2-yl)-1 H-pyrazol-4-yl, pyrimidin-5-yl, 2- cyclopropylpyrimid-5-yl, 3-cyclopropylpyrimid-5-yl, pyridazin-4-yl, 6- cyclopropylpyridazin-4-yl, benzo[d]isoxazol-3-yl, 2- isopropylbenzo[d]oxazol-6-yl, and 2-methylthiazol-5-yl.

29. A compound chosen from

frans-N-Hydroxy-2,3-diphenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-2-Cyclohexyl-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-N-Hydroxy-2-(2-isopropoxyphenyl)-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-2-(2-Fluorophenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 S*,2R*,3R*)-2-(2-Fluorophenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-2-(2-Bromophenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-2-(3-Bromophenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-2-(4-Bromophenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-N-Hydroxy-2-phenyl-3-o-tolylcyclopropanecarboxamide; (1 R*,2R*,3R*)-N-Hydroxy-2-phenyl-3-m-tolylcyclopropanecarboxamide; (1 R*,2R*,3R*)-N-Hydroxy-2-phenyl-3-p-tolylcyclopropanecarboxamide; (1 R*,2R*,3R*)-2-(4-(cyclopropanesulfonannido)phenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 S*,2R*,3R*)-2-Cyclopentyl-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-N-Hydroxy-2-(1 -methyl-1 H-pyrazol-4-yl)-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-N-Hydroxy-2-phenyl-3-(pyrimidin-5- yl)cyclopropanecarboxamide;

(1 R,2R,3R)-2-(2,3-Dihydrobenzo[b][1 ,4]dioxin-6-yl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-2-(8-Chloro-2,3-dihydrobenzo[b][1 ,4]dioxin-6-yl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 S,2R,3R)-2-(8-Chloro-2,3-dihydrobenzo[b][1 ,4]dioxin-6-yl)-3-(2- fluorophenyl)-N-hydroxycyclopropanecarboxamide;

(1 R*,2R*,3R*)-N-Hydroxy-2-phenyl-3-(pyridazin-4- yl)cyclopropanecarboxamide;

(1 R,2R,3R)-2-(2-Cyclopropylpyridin-4-yl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 S,2R,3R)-2-(2-Cyclopropylpyridin-4-yl)-3-(2-fluorophenyl)-N- hydroxycyclopropanecarboxamide;

(1 R,2R,3R)-2-(2-Cyclopropylpyridin-4-yl)-3-(4-fluorophenyl)-N- hydroxycyclopropanecarboxamide;

(1 R,2R,3R)-2-(2,2-Difluorobenzo[d][1 ,3]dioxol-5-yl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-N-Hydroxy-2-phenyl-3-(6-(trifluoromethyl)pyridin-3- yl)cyclopropanecarboxamide;

(1 R,2R,3R)-N-Hydroxy-2-phenyl-3-(2-(trifluoromethyl)pyridin-4- yl)cyclopropanecarboxamide;

(1 R,2R,3R)-N-Hydroxy-2-(1 -oxo-2-(2,2,2-trifluoroethyl)isoindolin-5-yl)-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-N-hydroxy-2-(2-isopropylbenzo[d]oxazol-6-yl)-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-N-Hydroxy-2-(3-(oxazol-5-yl)phenyl)-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-N-Hydroxy-2-(4-(oxazol-5-yl)phenyl)-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-2-(4-(1 H-imidazol-1 -yl)phenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-2-(4-(2-Cyclopropyloxazol-5-yl)phenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-N-Hydroxy-2-phenyl-3-(4-(2-phenyloxazol-5- yl)phenyl)cyclopropanecarboxamide;

(1 R*,2R*,3R*)-2-(4-(5-Fluoropyrimidin-2-yl)phenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-2-(3-(5-Fluoropyrimidin-2-yl)phenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-2-(4-(5-Cyclopropylpyrimidin-2-yl)phenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-2-(4-(4-Trifluoromethylpyrimidin-2-yl)phenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-2-(4-(5-Trifluoromethylpyrimidin-2-yl)phenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-N-Hydroxy-2-phenyl-3-(4-(pyridazin-3- yl)phenyl)cyclopropanecarboxamide;

(1 R*,2R*,3R*)-N -Hydroxy-2-phenyl-3-(4-(pyridazin-4- yl)phenyl)cyclopropanecarboxamide;

(1 R*,2R*,3R*)-N-Hydroxy-2-phenyl-3-(4-(pyrimidin-2- yl)phenyl)cyclopropanecarboxamide;

(1 R*,2R*,3R*)-N-Hydroxy-2-phenyl-3-(4-(pyrimidin-5- yl)phenyl)cyclopropanecarboxamide;

(1 R,2R,3R)-2-(4-(5-Chloropyrimidin-2-yl)phenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-N-Hydroxy-2-(4-(5-methylpyrimidin-2-yl)phenyl)-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-N-Hydroxy-2-(4-(5-methyl-1 H-imidazol-2-yl)phenyl)-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-2-(4-(2-cyclopropylisoindolin-5-yl)phenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-2-(3'-(Benzyloxy)-[1 ,1 '-biphenyl]-4-yl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-2-(4'-(9H-carbazol-9-yl)-[1 ,1 '-biphenyl]-4-yl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-N-hydroxy-2-(4-(4-methyl-3,4-dihydro-2H-benzo[b][1 ,4]oxazin- 7-yl)phenyl)-3-phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-N-Hydroxy-2-(4-(4-isopropylpiperazin-1 -yl)phenyl)-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-N-Hydroxy-2-(3-(4-isopropylpiperazin-1 -yl)phenyl)-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-N-Hydroxy-2-(4-(3,3-difluoropyrrolidin-1 -yl)phenyl)-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-2-(4-(3,3-Dimethylazetidin-1 -yl)phenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-2-(4-(2-Oxa-6-azaspiro[3.3]heptan-6-yl)phenyl)-N-hydroxy- 3-phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-2-(3-(Hexahydropyrrolo[1 ,2-a]pyrazin-2(1 H)-yl)phenyl)-N- hydroxy-3-phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-N-Hydroxy-2-phenyl-3-(3-(4-(pyrrolidin-1 -yl)piperidin-1 - yl)phenyl)cyclopropanecarboxamide;

(1 R,2R,3R)-2-(3-(6,7-Dihydropyrazolo[1 ,5-a]pyrimidin-4(5H)-yl)phenyl)-N- hydroxy-3-phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-N-Hydroxy-2-(4-(4-methylpiperazin-1 -yl)phenyl)-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*j-N-Hydroxy-2-(4-(oxazol-2-yl)phenyl)-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-N -Hydroxy-2-(4-(1 -methyl-1 H-imidazol-2-yl)phenyl)-3- phenylcyclopropanecarboxamide;

(1 R*,2S*,3S*)-2-(4-(5-Fluoropyrimidin-2-yl)phenyl)-N-hydroxy-1 -methyl-3- phenylcyclopropanecarboxamide;

(1 R*,2R*,3R*)-2-(4-(1 H-pyrazol-1 -yl)phenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-N-Hydroxy-2-phenyl-3-(5-(trifluoromethyl)pyridin-3- yl)cyclopropanecarboxamide;

(1 R,2R,3R)-2-(4-(1 -Benzyl-1 ,2,3,6-tetrahydropyridin-4-yl)phenyl)-N- hydroxy-3-phenylcyclopropanecarboxamide;

(1 S,2R,3R)-2-(2-fluorophenyl)-N-hydroxy-3-(4-(2-methyloxazol-5- yl)phenyl)cyclopropanecarboxamide;

(1 S,2R,3S)-2-(2-fluorophenyl)-N-hydroxy-1 -methyl-3-(4-(2-methyloxazol-5- yl)phenyl)cyclopropanecarboxamide;

(1 S,2R,3R)-2-(2-fluorophenyl)-N-hydroxy-3-(4-(3-methyl-1 H-pyrazol-1 - yl)phenyl)cyclopropanecarboxamide;

(1 S,2R,3R)-2-(2-fluorophenyl)-N-hydroxy-3-(4-(3-(trifluoromethyl)-1 H- pyrazol-1 -yl)phenyl)cyclopropanecarboxamide;

(1 S,2R,3R)-2-(2-fluorophenyl)-N-hydroxy-3-(4-(isopropyl(2- morpholinoethyl)amino)phenyl)cyclopropanecarboxamide;

(1 R,2R,3R)-2-(2-cyclopropylpyrimidin-5-yl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-2-(benzo[d]isoxazol-3-yl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-2-(6-cyclopropylpyridazin-4-yl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 S,2R,3R)-2-(2-fluorophenyl)-N-hydroxy-3-(6-(3-methyl-1 H-pyrazol-1 - yl)pyridin-3-yl)cyclopropanecarboxamide;

(1 S,2R3R)-2-(6-(5-chloropyrimidin-2-yl)pyridin-3-yl)-3-(2-fluorophenyl)-N- hydroxycyclopropanecarboxamide;

(1 R,2R,3R)-2-(5-chloro-6-(4-isopropylpiperazin-1 -yl)pyridin-3-yl)-N- hydroxy-3-phenylcyclopropanecarboxamide;

(1 S,2R,3R)-2-(2-fluorophenyl)-3-(6-(5-fluoropyrimidin-2-yl)pyridin-3-yl)-N- hydroxycyclopropanecarboxamide;

(1 S,2R,3R)-2-(2-fluorophenyl)-N-hydroxy-3-(6-(5-methylpyrimidin-2- yl)pyridin-3-yl)cyclopropanecarboxamide;

(1 R,2R,3R)-N-hydroxy-2-(6-(2-methyloxazol-5-yl)pyridin-3-yl)-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-2-(5-chloro-6-(2-methyloxazol-5-yl)pyridin-3-yl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 S,2R3R)-2-(2-fluorophenyl)-N-hydroxy-3-(2-(2,2,2- trifluoroethylamino)pyridin-4-yl)cyclopropanecarboxamide;

(1 R,2R,3R)-N-hydroxy-2-phenyl-3-(1 -(2,2,2-trifluoroethyl)-1 H-pyrazol-4- yl)cyclopropanecarboxamide;

(1 R,2R,3R)-2-(1 -cyclopropyl-1 H-pyrazol-4-yl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-N-hydroxy-2-phenyl-3-(1 -(1 -(2,2,2-trifluoroethyl)pipendin-4-yl)- 1 H-pyrazol-4-yl)cyclopropanecarboxamide;

(1 R,2R,3R)-2-(1 ,3-dimethyl-1 H-pyrazol-4-yl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R,2R,3S)-N-hydroxy-2-(2-methylthiazol-5-yl)-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-2-(8-chloro-1 ,2,3,4-tetrahydroquinolin-6-yl)-N-hydroxy-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-N-hydroxy-2-phenyl-3-(4-(2,2,2-trifluoroethyl)-2,3,4,5- tetrahydrobenzo[f][1 ,4]oxazepin-7-yl)cyclopropanecarboxamide; (1 R,2R,3R)-N-hydroxy-2-(1 -methyl-2-(2,2,2-trifluoroethyl)-1 ,2,3,4- tetrahydropyrrolo[1 ,2-a]pyrazin-7-yl)-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-2-(1 -fluoro-2-(2,2,2-trifluoroethyl)-1 ,2,3,4-tetrahydropyrrolo[1 ,2- a]pyrazin-7-yl)-N-hydroxy-3-phenylcyclopropanecarboxamide;

(1 R,2R,3R)-N-hydroxy-2-phenyl-3-(2-(2,2,2-trifluoroethyl)-1 ,2,3,4- tetrahydropyrrolo[1 ,2-a]pyrazin-7-yl)cyclopropanecarboxamide; (1 R,2R,3R)-N-hydroxy-2-phenyl-3-(7-(2,2,2-trifluoroethyl)-5,6,7,8- tetrahydroimidazo[1 ,2-a]pyrazin-2-yl)cyclopropanecarboxamide; (1 R,2R,3R)-N-hydroxy-2-phenyl-3-(2-(trifluoromethyl)imidazo[1 ,2-a]pyridin- 7-yl)cyclopropanecarboxamide

(1 R,2R,3R)-N-hydroxy-2-(imidazo[1 ,2-a]pyridin-3-yl)-3- phenylcyclopropanecarboxamide;

(1 R,2R,3R)-N-hydroxy-2-phenyl-3-(pyrrolo[1 ,2-a]pyrimidin-4- yl)cyclopropanecarboxamide;

(1 R,2R,3R)-N-hydroxy-2-(1 ,5-naphthyridin-4-yl)-3- phenylcyclopropanecarboxamide;

(1 S,2S,3R)-2-(2-cyclopropylpyridin-4-yl)-N-hydroxy-3-(2-methylthiazol-5- yl)cyclopropanecarboxamide;

(1 S,2S,3R)-2-(2-cyclopropylpyridin-4-yl)-N-hydroxy-3-(5- (trifluoromethyl)thiophen-2-yl)cyclopropanecarboxamide;

(1 R,2R,3R)-2-(1 -((5-fluoropyridin-2-yl)methyl)-1 H;pyrazol-4-yl)-N-hydroxy- 3-phenylcyclopropanecarboxamide

(1 S,2R,3S)-2-(3-fluoro-5-methylthiophen-2-yl)-N-hydroxy-3-(1 -methyl-1 H- pyrazol-4-yl)cyclopropanecarboxamide;

(1 S,2S,3R)-N-hydroxy-2-(1 -methyl-1 H-pyrazol-4-yl)-3-(5-methyl-3- (trifluoromethyl)thiophen-2-yl)cyclopropanecarboxamide;

(1 S,2S,3R)-N-hydroxy-2-(1 -methyl-1 H-pyrazol-4-yl)-3-(5-methylthiophen-2- yl)cyclopropanecarboxamide;

(1 R,2R,3R)-N-hydroxy-2-(1 -methyl-1 H-pyrazol-4-yl)-3-o- tolylcyclopropanecarboxamide;

(1 R,2R,3R)-N-hydroxy-2-(1 -methyl-1 H-pyrazol-4-yl)-3-(2- (trifluoronnethyl)phenyl)cyclopropanecarboxamide;

(1 S,2R,3R)-2-(2-chlorophenyl)-N-hydroxy-3-(1 -methyl-1 H-pyrazol-4- yl)cyclopropanecarboxamide;

(1 R,2R,3R)-2-(3-fluorophenyl)-N-hydroxy-3-(1 -methyl-1 H-pyrazol-4- yl)cyclopropanecarboxamide;

(1 R,2R,3R)-N-hydroxy-2-(1 -methyl-1 H-pyrazol-4-yl)-3-m- tolylcyclopropanecarboxamide;

(1 R,2R,3R)-N-hydroxy-2-(1 -methyl-1 H-pyrazol-4-yl)-3-(3- (trifluoromethyl)phenyl)cyclopropanecarboxamide;

(1 R,2R,3R)-2-(3-chlorophenyl)-N-hydroxy-3-(1 -methyl-1 H-pyrazol-4- yl)cyclopropanecarboxamide;

(1 S,2S,3R)-2-(2-cyclopropylpyridin-4-yl)-3-(3-fluoro-5-methylthiophen-2-yl)- N-hydroxycyclopropanecarboxamide;

(1 S,2S,3R)-2-(2-cyclopropylpyridin-4-yl)-N-hydroxy-3-(5-methyl-3- (trifluoromethyl)thiophen-2-yl)cyclopropanecarboxamide; (1 S,2S,3R)-2-(2-cyclopropylpyridin-4-yl)-N-hydroxy-3-(5-methylthiophen-2- yl)cyclopropanecarboxamide;

(1 R,2R,3R)-N-hydroxy-2-phenyl-3-(4-(5-(trifluoromethyl)-1 H-imidazol-2- yl)phenyl)cyclopropanecarboxamide;

(1 R,2R,3R)-2-(3-chloro-4-(5-methyl-1 H-imidazol-2-yl)phenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide; and

(1 R,2R,3R)-2-(3-fluoro-4-(5-methyl-1 H-imidazol-2-yl)phenyl)-N-hydroxy-3- phenylcyclopropanecarboxamide,

or a pharmaceutically acceptable salt thereof.

30. A pharmaceutical composition comprising a compound of any one of

claims 1 to 29, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

31 . A method of treating a condition or disorder mediated by at least one

histone deacetylase in a subject in need of such a treatment which method comprises administering to the subject a therapeutically effective amount of a compound of any one of claims 1 to 29, or a pharmaceutically acceptable salt thereof.

32. The method of claim 31 wherein the at least one histone deacetylase is HDAC-4.

33. The method of claim 31 wherein said condition or disorder involves a neurodegenerative pathology.

34. The method of claim 33 wherein the condition or disorder is Huntington's disease.