Histone deacetylase inhibitors

1. A compound of the formula (I):

wherein

Ar/Het is selected from the group consisting of pyrazolyl, thiazolyl, oxazolyl, imidazolyl, thienyl, furanyl, isoxazolyl, isothiazolyl, thiadiazolyl, oxadiazolyl, and 1,2,4-triazolyl;

Y is bond, CR c ═CR d , O, NR e , or S(O) m ;

a is 1-3;

b is 0-3;

m is 0-2;

each occurrence of R a and R b is independently selected from H, F, OH, C1-C6 alkyl, C3-C6 cycloalkyl, NH 2 , OCO—(C1-C6 alkyl), OCO—(C3-C6 cycloalkyl), C1-C6 alkoxy, C1-C6 fluoroalkoxy, and cyano;

each of R c and R d is, independently, selected from H, F, OH, C1-C6 alkyl, C3-C5 cycloalkyl, NH 2 , OCO—(C1-C6 alkyl), OCO—(C3-C5 cycloalkyl), C1-C6 alkoxy, C1-C6 fluoroalkoxy, and cyano;

each occurrence of R e is independently selected from H, C1-C6 alkyl, —C(═O)H, —C(═O)R h , C(═O)O(C1-C6 alkyl), C(═O)N(R i ) 2 , SO 2 —R h , wherein R h is selected from C1-C6 alkyl, CH 2 -(heteroaryl having 5-10 ring atoms), CH 2 —(C6-C10 aryl), and C6-C10 aryl; and each occurrence of R i is independently selected from H, C1-C6 alkyl, CH 2 -(heteroaryl having 5-10 ring atoms), CH 2 —(C6-C10 aryl), and C6-C10 aryl and the aryl or heteroaryl portion in R h and R i can be optionally substituted with one or more independently selected substituents selected from the group consisting of F, C1-C6 alkyl, fluoro C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 fluoroalkoxy, and cyano;

each of R4 and R5 is, independently, selected from H, C1-C6 alkyl and F;

R1 is:

(i) hydrogen; or

(ii) C6-C10 aryl, which is optionally substituted with from 1-3 R o ; or

(iii) monocyclic or bicyclic heteroaryl having from 5-10 ring atoms, which is optionally substituted with from 1-3 R o ; wherein from 1-4 of the ring atoms is/are a heteroatom independently selected from O, N, N—H, N—R o , and S; or

(iv) heterocyclyl having from 4-10 ring atoms, which is optionally substituted with from 1-3 R o ; wherein from 1-4 of the ring atoms is/are a heteroatom independently selected from O, N, N—H, N—R o , and S; and

each occurrence of R o is independently selected from the group consisting of: halogen; C1-C6 alkyl; fluoro(C1-C6alkyl); hydroxyl; hydroxy(C1-C4alkyl); C1-C6 alkoxy; fluoro(C1-C6alkoxy); (C1-C6 alkyl)C(O)—; (C1-C6 alkyl)NH—; (C1-C6 alkyl) 2 N—; formyl; formyl(C1-C4alkyl); cyano; cyano(C1-C4alkyl); benzyl; benzyloxy; SO 2 —(C1-C6alkyl); SO—(C1-C6alkyl); and nitro;

R2 is selected from H, F, Cl, CF 3 , CF 2 CF 3 , CH 2 CF 3 , OCF 3 , OCHF 2 , phenyl; phenyl substituted with from 1-3 substituents independently selected from F, OH, C1-C6 alkyl, fluoro(C1-C6 alkyl) C3-C6 cycloalkyl, NH 2 , C1-C6 alkoxy, C1-C6 fluoroalkoxy, and cyano; thienyl; thiazolyl; and pyrazol-1-yl; and

R3 is H, F, or Cl;

or a pharmaceutically acceptable salt thereof.

2. The compound or salt of claim 1 , wherein each occurrence of R a and R b is independently selected from H, F, and C1-C6 alkyl.

3. The compound or salt of claim 2 , wherein each occurrence of R a and R b is H.

4. The compound or salt of claim 1 , wherein Y is CR c ═CR d , O, or NR e .

5. The compound or salt of claim 1 , wherein each of R4 and R5 is H.

6. The compound or salt of claim 1 , wherein one of the following applies: (i) R2 is F, Cl, CF 3 , CF 2 CF 3 , CH 2 CF 3 , OCF 3 , OCHF 2 , phenyl; phenyl substituted with from 1-3 substituents independently selected from F, OH, C1-C6 alkyl, fluoro(C1-C6 alkyl), C3-C6cycloalkyl, NH 2 , C1-C6alkoxy, C1-C6 fluoroalkoxy, and cyano; thienyl; thiazolyl; or pyrazol-1-yl, and R3 is hydrogen; or (ii) R2 is hydrogen, and R3 is F or Cl.

7. The compound or salt of claim 1 , wherein each of R2 and R3 is hydrogen.

8. A compound selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition comprising a compound, or pharmaceutically acceptable salt thereof, as claimed in claim 1 and a pharmaceutically acceptable carrier.

10. The compound or salt of claim 1 , wherein Y is CR c ═CR d .

11. The compound or salt of claim 1 , wherein —Y—[C(R a ) 2 ] a —[C(R b ) 2 ] b — is —CH═CH—C(R a ) 2 —C(R b ) 2 .

12. The compound or salt of claim 1 , wherein —Y—[C(R a ) 2 ] a —[C(R b ) 2 ] b — is —CH═CH—CH 2 — or —CH═CH—CH 2 —CH 2 —.

13. The compound or salt of claim 1 , wherein Y is O or NR e .

14. The compound or salt of claim 1 , wherein Ar/Het is pyrazolyl.

15. The compound or salt of claim 1 , wherein R1 is phenyl.

16. The compound or salt of claim 1 , wherein R1 is pyridyl.

17. The compound or salt of claim 1 , wherein R1 is H.

18. The compound or salt of claim 1 , wherein Ar/Het is pyrazolyl, R a and R b are H, Y is a bond, and R1 is H.

19. The compound or salt of claim 1 , wherein Ar/Het is pyrazolyl, R a and R b are H, and R1 is phenyl.

20. The compound or salt of claim 1 , wherein Ar/Het is pyrazolyl, R a and R b are H, Y is O or NR e , and R1 is phenyl.

21. The compound or salt of claim 1 , wherein Ar/Het is pyrazolyl, R a and R b are H, Y is O, and R1 is phenyl.

22. The compound or salt of claim 1 , wherein Ar/Het is pyrazolyl, R a and R b are H, Y is CR c ═CR d , and R1 is phenyl.

23. The compound or salt of claim 1 , wherein Ar/Het is pyrazolyl, R a and R b are H, Y is a bond, and R1 is phenyl.

24. The compound or salt of claim 1 , wherein Ar/Het is pyrazolyl, Y is a bond, CR c ═CR d , O, or NR e , and R1 is phenyl.

25. The compound or salt of claim 1 , wherein Ar/Het is pyrazolyl, Y is a CR c ═CR d , and R1 is phenyl.

26. The compound or salt of claim 1 , wherein Ar/Het is pyrazolyl, Y is a bond, and R1 is phenyl.