Oxadiazole HDAC inhibitors

1. A compound having the formula:

wherein:

R 1 is fluoro(C 1 -C 4 )alkyl containing at least 2 fluoro atoms;

Y is a bond X 1 is O, X 2 and X 3 are N;

Q is -phenyl-C(═O)— or —(C 3 -C 6 )cycloalkyl-C(═O)—, wherein the (C 3 -C 6 )cycloalkyl, or phenyl moiety is optionally substituted by 1, 2 or 3 groups independently selected from (C 1 -C 4 )alkyl, halogen, cyano, halo(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, and halo(C 1 -C 4 )alkoxy;

is an optionally substituted, saturated 4, 5, 6 or 7 membered heterocyclic ring, optionally containing one additional nitrogen atom, where said 4, 5, 6 or 7 membered heterocyclic ring is optionally substituted by 1 or 2 groups independently selected from (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, halogen, cyano, —C(═O)OR Y , and —(C 1 -C 2 )C(═O)OR Y , where each R Y is independently selected from H and methyl;

L is a bond or methylene;

R 2 is 5-6 membered heteroaryl, phenyl, —C(O)-(5-6 membered heteroaryl), or —C(O)-phenyl,

wherein the 5-membered heteroaryl moiety of said 5-6 membered heteroaryl group or said —C(O)-(5-6 membered heteroaryl) group contains one oxygen or sulfur ring heteroatom, and optionally contains 1 additional nitrogen ring atom and the 6-membered heteroaryl moiety of said 5-6 membered heteroaryl group or said —C(O)-(5-6 membered heteroaryl) group contains 1 or 2 nitrogen ring heteroatoms,

wherein any of said 5-6 membered heteroaryl or phenyl moieties is optionally substituted by 1 or 2 groups independently selected from (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, halogen, cyano and (C 1 -C 4 )alkoxy,

or said 5-6 membered heteroaryl group is optionally substituted by an optionally substituted phenyl group, wherein said optionally substituted phenyl group is optionally substituted by 1 or 2 groups independently selected from (C 1 -C 4 )alkyl, halogen, cyano, halo(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, halo(C 1 -C 4 )alkoxy, and hydroxyl;

or a salt thereof.

2. The compound or salt according to claim 1 , wherein R 1 is CHF 2 or CF 3 .

3. The compound or salt according to claim 1 , wherein R 1 is CF 3 .

4. The compound or salt according to claim 1 , wherein A is a phenyl group optionally substituted by 1-2 groups independently selected from (C 1 -C 4 )alkyl, halogen, cyano, halo(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, and halo(C 1 -C 4 )alkoxy.

5. The compound or salt according to claim 1 , wherein:

R 1 is —CF 3 ;

Q is -phenyl-C(═O)— or —(C 3 -C 6 )cycloalkyl-C(═O)—, wherein said phenyl or (C 3 -C 6 )cycloalkyl is optionally substituted by chloro, fluoro, cyano, methoxy, methyl, or trifluoromethyl;

L is a bond;

R 2 is phenyl, pyridyl, pyrimidinyl, thiazolyl, or oxazolyl, where said phenyl, pyridyl, pyrimidinyl, thiazolyl, or oxazolyl is optionally substituted with 1 or 2 groups independently selected from (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, halogen, cyano and (C 1 -C 4 )alkoxy,

or is optionally substituted by an optionally substituted phenyl group, wherein said optionally substituted phenyl is optionally substituted by 1 or 2 groups independently selected from (C 1 -C 4 )alkyl, halogen, cyano, halo(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, and halo(C 1 -C 4 )alkoxy;

is an optionally substituted saturated 5 or 6-membered heterocyclic ring, optionally containing one additional nitrogen ring atom, where said 5 or 6-membered heterocyclic ring is optionally substituted by 1 or 2 groups independently selected from (C 1 -C 2 )alkyl, halo(C 1 -C 2 )alkyl, cyano, —C(═O)OR y , and —(C 1 -C 2 )C(═O)OR y , where each R y is independently selected from H and methyl.

6. The compound or salt according to claim 3 , wherein

Q is unsubstituted phenyl-C(═O);

X is NR X or a bond, where R X is H;

B is 1,4-diazepanyl, piperazinyl or piperidinyl, optionally substituted by 1 or 2 groups independently selected from methyl and —C(═O)OH;

L is a bond;

R 2 is phenyl, pyridyl, pyrimidinyl, thiazolyl, or oxazolyl,

wherein the phenyl, pyridyl, pyrimidinyl, thiazolyl or oxazolyl is optionally substituted with 1 or 2 groups independently selected from methyl, trifluoromethyl, fluoro, cyano, and methoxy,

or wherein the phenyl, pyridyl, pyrimidinyl, thiazolyl or oxazolyl is optionally substituted by phenyl or fluoro-phenyl.

7. A compound which is:

(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)(4-(5-(trifluoromethyl)pyridin-2-yl)-1,4-diazepan-1-yl)methanone,

6-(4-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)piperazin-1-yl)nicotinonitrile,

4-(4-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)piperazin-1-yl)benzonitrile,

6-(2-methyl-4-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)piperazin-1-yl)nicotinonitrile,

6-(3-methyl-4-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)piperazin-1-yl)nicotinonitrile,

6-(3,5-dimethyl-4-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)piperazin-1-yl)nicotinonitrile,

4-(5-cyanopyridin-2-yl)-1-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)piperazine-2-carboxylic acid,

6-(2,6-dimethyl-4-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)piperazin-1-yl)nicotinonitrile,

6-(3,3-dimethyl-4-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)piperazin-1-yl)nicotinonitrile,

6-(4-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)-1,4-diazepan-1-yl)nicotinonitrile,

(4-methyl-3-(4-phenylthiazol-2-yl)piperazin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone,

(4-(5-methoxypyridin-2-yl)piperazin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone,

(3-(4-(4-fluorophenyl)thiazol-2-yl)piperidin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone,

(3-(5-(4-fluorophenyl)oxazol-2-yl)piperidin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone,

(4-(3-methoxyphenyl)piperazin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone,

2-(4-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)piperazin-1-yl)nicotinonitrile,

3-fluoro-4-(4-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)piperazin-1-yl)benzonitrile,

(4-(pyrimidin-2-yl)piperazin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone,

(3-((4-(4-fluorophenyl)thiazol-2-yl)methyl)azetidin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone,

(4-(4-methylthiazol-2-yl)piperazin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone,

(4-((2-(4-fluorophenyl)thiazol-4-yl)methyl)piperazin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone,

(4-((2-(4-fluorophenyl)oxazol-4-yl)methyl)piperazin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone,

(2-phenylthiazol-4-yl)(4-(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoyl)piperazin-1-yl)methanone, or

((1S,4S)-5-(pyridin-2-yl)-2,5-diazabicyclo[2.2.1]heptan-2-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone,

or a pharmaceutically acceptable salt thereof.