1,2,4-oxadiazole derivatives as histone deacetylase 6 inhibitors

Abstract

The invention relates to compounds of Formula (I) as described herein, useful as histone deacetylase 6 (HDAC6) inhibitors. The invention also relates to pharmaceutical compositions comprising these compounds and to their use in therapy.

1 . A compound of Formula (I) or a salt thereof: 
       
         
           
           
               
               
           
         
         wherein 
         m is 0, 1 or 2; 
         each R 1  is independently selected from halo, methyl and trifluoromethyl; 
         A is selected from:
 i) a 5- or 6-membered monocyclic or 9- or 10-membered bicyclic heteroaryl ring that is fully aromatic, and 
 ii) a 9- or 10-membered bicyclic heteroaryl ring consisting of a 5- or 6-membered monocyclic heteroaryl ring fused to a saturated or partially unsaturated carbocyclic or heterocyclic ring, wherein the 9- or 10-membered bicyclic heterocyclic ring is linked to the rest of the molecule through the 5- or 6-membered monocyclic heteroaryl ring, 
 
         wherein A contains one ring N atom at a position adjacent to the ring atom through which ring A is attached to the rest of the molecule, wherein A optionally contains from 1 to 3 additional ring heteroatoms selected independently from N, O and S, and 
         wherein A is optionally substituted with one or two R 2  and in addition A is optionally substituted with one R 3 ; 
         each R 2  is independently selected from halo, C 1-6  alkyl, C 1-6  haloalkyl, C 3-7  cycloalkyl and —(C 1-6  alkylene)-OR 4 ; 
         R 3  is selected from -L 1 -R 5 , -L 2 -OR 6 , -L 3 -NR 7 R 8 , -L 4 -CONR 9 R 10 , -L 5 -NR 11 COR 12 , —Y-L 6 -OR 6  and —Y-L 7 - NR 7 R 8 ; 
         L 1 , L 2 , L 3 , L 4  and L 5  are each independently selected from a bond and C 1-6  alkylene; 
         L 6  and L 1  are each independently selected from C 2-6  alkylene; 
         each Y is independently selected from —O—, —NR 13 —, —CONR 14 — and —NR 15 CO—; 
         each R 4  is independently selected from hydrogen, C 1-6  alkyl, C 1-6  haloalkyl, C 3-7  cycloalkyl and C 3-7  cycloalkyl-C 1-6  alkyl; 
         each R 5  is independently selected from carbocyclyl, aryl, heterocyclyl and heteroaryl, wherein the carbocyclyl, the aryl, the heterocyclyl and the heteroaryl are each optionally substituted with one or more R 16 ; 
         R 6  and R 12  are each independently selected from hydrogen, C 1-6  alkyl, C 1-6  haloalkyl and -L 1 -R 5 ; 
         R 7  and R 8  are each independently selected from hydrogen, C 1-6  alkyl, C 1-6  haloalkyl, —(C 1-6  alkylene)-OR 4  and -L 1 -R 5 ; 
         R 9  and R 10  are each independently selected from hydrogen, C 1-6  alkyl, C 1-6  haloalkyl, —(C 1-6  alkylene)-OR 4  and -L 1 -R 5 , or R 9  and R 10  taken together with the N atom to which they are attached form a saturated 4- to 12-membered heterocyclic ring optionally containing one additional heteroatom selected from N, O and S, wherein said heterocyclic ring is optionally substituted with one or more R 16 ; 
         R 11 , R 13 , R 14  and R 15  are each independently selected from hydrogen, C 1-6  alkyl, C 1-6  haloalkyl, C 3-7  cycloalkyl, C 3-7  cycloalkyl-C 1-6  alkyl and —(C 1-6  alkylene)-OR 4 ; 
         each R 16  is independently selected from C 1-6  alkyl, C 1-6  haloalkyl, halo, C 1-6  alkoxy, C 1-6  haloalkoxy, —OH, —NR 17 R 18 , —COR 19 , —CN, -L 8 -carbocyclyl, -L 8 -aryl, -L 8 -heterocyclyl and -L 8 -heteroaryl, wherein the carbocyclyl in -L 8 -carbocyclyl, the aryl in -L 8 -aryl, the heterocyclyl in -L 8 -heterocyclyl and the heteroaryl in -L 8 -heteroaryl are each optionally substituted with one or more R 20 ; 
         each L 8  is independently selected from a bond and C 1-6  alkylene; 
         R 17  and R 18  are each independently selected from hydrogen, C 1-6  alkyl, C 1-6  haloalkyl, C 3-7  cycloalkyl and C 3-7  cycloalkyl-C 1-6  alkyl; 
         R 19  is selected from hydrogen, C 1-6  alkyl and C 1-6  haloalkyl; and 
         each R 20  is independently selected from C 1-6  alkyl, C 1-6  haloalkyl, halo, C 1-6  alkoxy, C 1-6  haloalkoxy, —OH, —NR 17 R 18 , —COR 19  and —CN. 
       
     
     
         2 . The compound of  claim 1 , wherein A is selected from:
 i) a 5- or 6-membered monocyclic or 9- or 10-membered bicyclic heteroaryl ring that is fully aromatic, and   ii) a 9- or 10-membered bicyclic heteroaryl ring consisting of a 5- or 6-membered monocyclic heteroaryl ring fused to a saturated or partially unsaturated carbocyclic or heterocyclic ring, wherein the 9- or 10-membered bicyclic heterocyclic ring is linked to the rest of the molecule through the 5- or 6-membered monocyclic heteroaryl ring,   
       wherein A contains one ring N atom at a position adjacent to the ring atom through which ring A is attached to the rest of the molecule, wherein A optionally contains from 1 to 3 additional ring N atoms, and wherein A is optionally substituted with one or two R 2  and in addition A is optionally substituted with one R 3 . 
     
     
         3 . The compound of  claim 1 , wherein A is a 5- or 6-membered monocyclic or 9- or 10-membered bicyclic heteroaryl ring that is fully aromatic, wherein A contains one ring N atom at a position adjacent to the ring atom through which ring A is attached to the rest of the molecule, wherein A optionally contains from 1 to 3 additional ring N atoms, and wherein A is optionally substituted with one or two R 2  and in addition A is optionally substituted with one R 3 . 
     
     
         4 . The compound of  claim 1 , wherein A is selected from the cyclic groups listed below: 
       
         
           
           
               
               
           
         
         wherein A is optionally substituted with one or two R 2  and in addition A is optionally substituted with one R 3 . 
       
     
     
         5 . The compound of  claim 1 , wherein A is selected from the cyclic groups listed below: 
       
         
           
           
               
               
           
         
         wherein A is optionally substituted with one or two R 2  and in addition A is optionally substituted with one R 3 . 
       
     
     
         6 . The compound of  claim 1 , wherein the compound has formula (IIa) or (IIb), or a salt thereof 
       
         
           
           
               
               
           
         
         wherein one of Z 1 , Z 2  and Z 3  is H and the others are independently selected from H and R 2 . 
       
     
     
         7 . The compound of  claim 1 , wherein the compound has formula (IIIa) or (IIIb), or a salt thereof 
       
         
           
           
               
               
           
         
         wherein one of Z 1 , Z 2  and Z 3  is R 3  or H, and the others are independently selected from H and R 2 . 
       
     
     
         8 . The compound of  claim 1 , wherein the compound has formula (IVa), or a salt thereof 
       
         
           
           
               
               
           
         
         wherein one of Z 1 , Z 2 , Z 3  and Z 4  is selected from R 2 , R 3  and H, and the others are independently selected from H and R 2 , with the proviso that only up to two of Z 1 , Z 2 , Z 3  and Z 4  are R 2 . 
       
     
     
         9 . The compound of  claim 1 , wherein the compound has formula (IVb), or a salt thereof 
       
         
           
           
               
               
           
         
         wherein one of Z 1 , Z 2 , Z 3  and Z 4  is selected from R 2 , R 3  and H, and the others are independently selected from H and R 2 , with the proviso that only up to two of Z 1 , Z 2 , Z 3  and Z 4  are R 2 . 
       
     
     
         10 . The compound of any one of  claims 1  to  9 , wherein m is 0. 
     
     
         11 . The compound of any one of  claims 1  to  10 , wherein R 3  is selected from -L 1 -R 5 , -L 2 -OR 6 , -L 3 -NR 7 R 8 , —CONR 9 R 10 , —NR 11 COR 12  and —Y-L 7 -NR 7 R 8 . 
     
     
         12 . The compound of any one of  claims 1  to  11 , wherein R 3  is -L 1 -R 5 . 
     
     
         13 . The compound of any one of  claims 1  to  11 , wherein R 3  is —CONR 9 R 10  or —NR 11 COR 12 . 
     
     
         14 . The compound of any one of  claims 1  to  11 , wherein R 3  is —Y-L 7 -NR 7 R 8 , and Y is selected from —O— and —NR 13 —. 
     
     
         15 . The compound of any one of  claims 1  to  11 , wherein R 3  is —OR 6 , wherein R 6  is -L 1 -R 5 , or R 3  is —NR 7 R 8 , wherein one of R 7  or R 8  is -L 1 -R 5 . 
     
     
         16 . The compound of any one of  claims 1  to  11 , wherein R 3  is -L 2 -OR 6  or -L 3 -NR 7 R 8 , wherein L 2  and L 3  are each independently selected from C 1-6  alkylene. 
     
     
         17 . The compound of any one of  claims 1  to  16 , wherein each R 2  is independently selected from C 1-4  alkyl, C 1-4  haloalkyl and —(C 1-4  alkylene)-OR 4 . 
     
     
         18 . The compound of  claim 1 , which is a compound selected from
 3-(2-(1-Butyl-1H-pyrrolo[2,3-c]pyridin-5-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   3-(2-(1-Propyl-1H-pyrrolo[2,3-c]pyridin-5-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   1-Butyl-N,N-dimethyl-5-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-yl)-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,   N,N-Diethyl-3-((4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-5-yl)oxy)propan-1-amine,   1-Butyl-N-ethyl-5-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-yl)-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,   4-(3-((4′-(5-(Trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-5-yl)oxy)propyl)morpholine,   3-(5′-(3-(4,4-Difluoropiperidin-1-yl)propoxy)-[2,2′-bipyridin]-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   3-(2-(3-(Piperidin-1-ylmethyl)-1-propyl-1H-pyrrolo[2,3-c]pyridin-5-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   4-((1-Propyl-5-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)methyl)morpholine,   N-Butyl-3-methoxy-N-(4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-5-yl)propanamide,   N-(Cyclopropylmethyl)-N-methyl-4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-5-amine,   N1,N1-Diethyl-N3-(4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-5-yl)propane-1,3-diamine,   N-(3-(4,4-Difluoropiperidin-1-yl)propyl)-N-methyl-4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-5-amine,   N,N-Diethyl-3-(2-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-yl)pyrimidin-5-yloxy)propan-1-amine,   N1,N1-Diethyl-N3-methyl-N3-(4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-2,2′-bipyridin-5-yl)propane-1,3-diamine,   3-(2-(1-(Tetrahydro-2H-pyran-4-yl)-1H-pyrrolo[3,2-c]pyridin-6-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   N-Ethyl-N-phenethyl-3-((4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-5-yl)oxy)propan-1-amine,   2-Phenyl-N-(4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-5-yl)acetamide,   3-(2-(1-((Tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrrolo[3,2-c]pyridin-6-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   3-(4′-(2-(4,4-Difluoropiperidin-1-yl)ethoxy)-[2,2′-bipyridin]-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   4-(2-((4′-(5-(Trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-4-yl)oxy)ethyl)morpholine,   N,N,1-Trimethyl-5-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-yl)-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,   3-(2-(1-Propyl-3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   1-Butyl-N,N-diethyl-5-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-yl)-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,   3-(2-(1-(2-Methoxyethyl)-1H-pyrrolo[2,3-c]pyridin-5-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   2-(4,4-Difluoropiperidin-1-yl)-N-(4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-4-yl)acetamide,   N-(2-(4,4-Difluoropiperidin-1-yl)ethyl)-4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-4 amine,   3-(2-(3-(Piperidin-1-ylmethyl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   3-(2-(1-(2-(4,4-Difluoropiperidin-1-yl)ethyl)-1H-pyrrolo[3,2-c]pyridin-6-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   1-Methyl-N-(4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-5-yl)piperidine-4-carboxamide,   3-Phenyl-N-(4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-4-yl)propanamide,   2-Cyclobutyl-N-(4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-4-yl)acetamide,   N-(Piperidin-3-yl)-4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridine]-4-carboxamide,   3-(5′-(3-(1H-Pyrazol-1-yl)propoxy)-[2,2′-bipyridin]-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   (1-Propyl-5-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)methanol,   3-(2-(3-(Methoxymethyl)-1-propyl-1H-pyrrolo[2,3-c]pyridin-5-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   4-((1-Propyl-5-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)methyl)morpholine,   3-(2-(1H-Pyrrolo[3,2-c]pyridin-6-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   3-(2-(1-(Pyridin-4-ylmethyl)-1H-pyrrolo[3,2-c]pyridin-6-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   N-((1-Methylpiperidin-4-yl)methyl)-4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridine]-4-carboxamide,   N-((1-Methylpiperidin-4-yl)methyl)-4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridine]-5-carboxamide,   3-(2-(1-(1-(2,2,2-Trifluoroethyl)piperidin-4-yl)-1H-pyrrolo[3,2-c]pyridin-6-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   3-(2-(1-Methyl-3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   3-(2-(1-Butyl-3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   N-Methyl-3-(4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-2,2′-bipyridin-5-yloxy) propan-1-amine,   1-(1-Butyl-5-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)-N,N-dimethylmethanamine,   3-(2-(1H-Pyrazolo[4,3-b]pyridin-3-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   N-(4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-4-yl)piperidine-3-carboxamide,   1-(2-Methoxyethyl)-N,N-dimethyl-5-(4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)pyridin-2-yl)-1H-pyrrolo[2,3-c]pyridine-2-carboxamide,   3-(2-(1-(2-Methoxyethyl)-3-(1H-pyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridin-5-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   3-(2-(1-Methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   3-(2-(1-(2-Methoxyethyl)-1H-pyrrolo[3,2-c]pyridin-6-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   3-(2-(1-(Pyridin-3-ylmethyl)-1H-pyrrolo[3,2-c]pyridin-6-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   3-(2-(1-(Pyridin-2-ylmethyl)-1H-pyrrolo[3,2-c]pyridin-6-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   2-(Methyl(3-((4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-5-yl)oxy)propyl)amino)ethan-1-ol,   3-(2-(1-(2-Methoxyethyl)-1H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   3-(2-(2-(2-Methoxyethyl)-2H-pyrazolo[3,4-c]pyridin-5-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   3-(2-(1H-Pyrazolo[3,4-b]pyridin-1-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   N,N-Dimethyl-3-((4′-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)-[2,2′-bipyridin]-5-yl)oxy)propan-1-amine,   3-(2-(1-Methyl-1H-pyrazolo[4,3-b]pyridin-3-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   3-(2-(1-(2-Methoxyethyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   3-(2-(1-Ethyl-1H-pyrazolo[4,3-b]pyridin-3-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   3-(2-(1-(2-(1-Methyl-1H-imidazol-2-yl)ethyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole, and   3-(2-(1-((1-Methyl-1H-pyrazol-4-yl)methyl)-1H-pyrrolo[3,2-c]pyridin-6-yl)pyridin-4-yl)-5-(trifluoromethyl)-1,2,4-oxadiazole,   or a salt thereof.   
     
     
         19 . A pharmaceutical composition which comprises a compound of any one of  claims 1  to  18  or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
     
     
         20 . A compound of any one of  claims 1  to  18 , or a pharmaceutically acceptable salt thereof, for use as a medicament. 
     
     
         21 . A compound of any one of  claims 1  to  18 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of  claim 19 , for use in the treatment of a disease associated with HDAC6. 
     
     
         22 . A compound of any one of  claims 1  to  18 , or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of  claim 19 , for use in the treatment of a disease selected from cancer, an autoimmune or inflammatory disease, transplant rejection, a ciliopathy, a disease of the nervous system, a mental or behavioral disorder, an infectious disease, a cardiovascular disease, muscle atrophy and cachexia. 
     
     
         23 . A method for treating a disease associated with HDAC6, comprising administering a therapeutically effective amount of a compound of any one of  claims 1  to  18 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof. 
     
     
         24 . A method for treating a disease selected from cancer, an autoimmune or inflammatory disease, transplant rejection, a ciliopathy, a disease of the nervous system, a mental or behavioral disorder, an infectious disease, a cardiovascular disease, muscle atrophy and cachexia, comprising administering a therapeutically effective amount of a compound of any one of  claims 1  to  18 , or a pharmaceutically acceptable salt thereof, to a patient in need thereof. 
     
     
         25 . Use of a compound of any one of  claims 1  to  18 , or pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment of a disease associated with HDAC6. 
     
     
         26 . Use of a compound of any one of  claims 1  to  18 , or pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment of a disease selected from cancer, an autoimmune or inflammatory disease, transplant rejection, a ciliopathy, a disease of the nervous system, a mental or behavioral disorder, an infectious disease, a cardiovascular disease, muscle atrophy and cachexia. 
     
     
         27 . Use of a compound of any one of  claims 1  to  18 , or pharmaceutically acceptable salt thereof, for treating a disease associated with HDAC6. 
     
     
         28 . Use of a compound of any one of  claims 1  to  18 , or pharmaceutically acceptable salt thereof, for treating a disease selected from cancer, an autoimmune or inflammatory disease, transplant rejection, a ciliopathy, a disease of the nervous system, a mental or behavioral disorder, an infectious disease, a cardiovascular disease, muscle atrophy and cachexia. 
     
     
         29 . The compound for use according to any one of  claims 20  to  22 , or the pharmaceutical composition for use according to  claim 21  or  22 , or the method of  claim 23  or  24 , or the use of any one of  claims 25  to  28 , wherein the patient to be treated is a human. 
     
     
         30 . In vitro method of inhibiting HDAC6, the method comprising applying a compound of any one of  claims 1  to  18 , or a pharmaceutically acceptable salt thereof, to a sample. 
     
     
         31 . In vitro use of a compound of any one of  claims 1  to  18 , or a pharmaceutically acceptable salt thereof, as an HDAC6 inhibitor.