US2014045850A1PendingUtilityA1

Inhibitors of histone deacetylase

47
Assignee: METHYLGENE INCPriority: Nov 2, 2007Filed: Mar 14, 2013Published: Feb 13, 2014
Est. expiryNov 2, 2027(~1.3 yrs left)· nominal 20-yr term from priority
A61P 43/00A61P 35/00C07D 413/04C07D 417/14C07D 333/24C07D 277/30C07D 261/18C07D 401/04C07D 231/12C07D 207/34C07D 417/04C07D 239/38C07D 403/10C07D 333/38C07D 263/34C07D 307/91C07D 307/85C07D 267/20C07D 231/14C07D 235/18C07C 311/29C07D 207/327C07D 213/64C07D 277/593C07D 317/60C07D 239/28C07D 277/64C07D 417/12C07D 213/61C07C 259/10
47
PatentIndex Score
0
Cited by
0
References
0
Claims

Abstract

This invention relates to compounds and methods for the inhibition of HDAC enzymatic activity. More particularly, the invention provides for compounds of formula (I), (I) and N-oxides, hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, and racemic and scalemic mixtures, diastereomers and enantiomers thereof, wherein L, M, n, R, W, X and Y are as defined in the specification.

Claims

exact text as granted — not AI-modified
1 .- 43 . (canceled) 
     
     
         44 . A compound of the formula (I): 
       
         
           
           
               
               
           
         
         and or an N-oxide, hydrate, solvate, pharmaceutically acceptable salt, prodrug or complex thereof, in the form of a racemic or scalemic mixture, tautomer, diastereomer or enantiomer thereof, wherein 
       
       
         
           
           
               
               
           
         
          is a five-membered heteroaryl; 
         W is N or —C═; 
         M is —C(O)N(H)OH; 
         R 1  and R 2  is independently selected from the group consisting of —H, -alkyl, -aryl, -aryl-aryl, -hetetoaryl, heteroaryl-aryl, heteroaryl-heteroaryl, alkyl-heteroaryl and -alkyl-aryl, wherein each aryl and heteroaryl moiety is optionally substituted; 
         R is selected from the group consisting of H, alkyl, halo, hydroxy, nitro, C 1 -C 4 alkyl, —NR 1 R 2 , —OR 1 , aryl, heteroaryl, alkyloxy and CF 3 ; 
         n is an integer from 0 to 1; 
         L is selected from the group consisting of aryl, heteroaryl, cycloalkyl, heterocyclyl, fused aryl, fused heterocyclyl, fused cycloalkyl, -alkenyl-aryl, -aryl-heteroaryl, -heteroaryl-aryl, -alkynyl-aryl, -alkyl-aryl, —SO 2 —N(R 1 )—C 0 -C 4 alkyl-aryl, —N(R 1 )-aryl, —CF 3 , -t-Bu, —NR 1 SO 2 -aryl, halo, —N(R 1 )C(O)-aryl and —S-aryl, wherein each aryl, heteroaryl, cycloalkyl and heterocyclyl moiety is optionally substituted with 1 to 3 independently selected substituents, and each of which is optionally fused to one or more aryl, heterocyclic or heteroaryl rings, or one or more saturated or partially unsaturated cycloalkyl or heterocyclyl rings, each of which ring is optionally substituted, 
         wherein a heteroaryl moiety in 
       
       
         
           
           
               
               
           
         
          is optionally connected to a cycloalkyl, heterocyclyl, aryl or heteroaryl in L by a bond or by a bridging substituent; and 
         Y is selected from the group consisting of halo, alkoxy, aryl, heterocyclyl, heteroaryl, —N(R 1 )—C(O)-alkyl-aryl, —C(O)—N(R 1 )-aryl-O-aryl, —N(R 1 )—SO 2 -aryl, -alkyl-aryl, -alkyl-heteroaryl, -aryl-heterocyclyl, -heterocyclyl-alkyl-aryl, heterocyclyl-alkyl-heteroaryl, -heterocyclyl-C(O)-aryl, —CH(aryl) 2 , -heterocyclyl-C(O)-alkyl, -heterocyclyl-C(O)-heterocyclyl, -heterocyclyl-C(O)—O-alkyl, -heterocyclyl-SO 2 -alkyl, -heterocyclyl-SO 2 -aryl, -heterocyclyl-alkyl-heteroaryl, -heterocyclyl-SO 2 -aryl-N(R 1 )—C(O)-alkyl, -alkyl-O-aryl, -alkyl-O—C(O)—N(R 1 )-alkyl-aryl, -alkyl-N(R 1 )-alkyl-aryl, —C(O)—N(R 1 )-aryl, —N(R 1 )—C(O)—O-alkyl-aryl, —N(R 1 )—SO 2 -alkyl-aryl, —N(R 1 )—SO 2 -aryl and —N(R 1 )—SO 2 -heteroaryl, wherein each aryl, heteroaryl and heterocyclyl moiety is optionally substituted with 1 to 3 independently selected substituents, and each of which is optionally fused to one or more aryl, heterocyclic or heteroaryl rings, or one or more saturated or partially unsaturated cycloalkyl or heterocyclyl rings, each of which ring is optionally substituted, 
       
       with the proviso that 
       
         
           
           
               
               
           
         
       
       is not isoxazol or pyrrole. 
     
     
         45 . The compound according to  claim 44 , having the Formula (Ia): 
       
         
           
           
               
               
           
         
       
     
     
         46 . The compound according to  claim 44 , wherein 
       
         
           
           
               
               
           
         
       
       is selected from the group consisting of 
       
         
           
           
               
               
           
         
         wherein A 1 , A 2 , A 3 , A 4  and A 5  form a 5-membered heteroaryl ring, wherein A 1  and A 3  are selected from the group consisting of carbon, nitrogen, —S— and —O—, A 4  is carbon and A 2  and A 5  are nitrogen or carbon, provided that at least one of A 2  and A 5  is carbon, and wherein * represents the point of attachment to group L and ** represents the point of attachment to group Y. 
       
     
     
         47 . The compound according to  claim 44 , wherein n is 0. 
     
     
         48 . The compound according to  claim 44 , wherein L is aryl or heteroaryl, each of which is optionally substituted with 1, 2 or 3 independently selected substituents. 
     
     
         49 . The compound according to  claim 44 , wherein 
       
         
           
           
               
               
           
         
       
       is 
       
         
           
           
               
               
           
         
         n is 1; 
         R is H; 
         L is aryl or N(R 1 )SO 2 -aryl, wherein said aryl moiety is optionally substituted with 1, 2 or 3 independently selected substituents; 
         Y is aryl, heteroaryl, or aryl-heterocyclyl, wherein said aryl and heteroaryl moieties are optionally substituted with 1, 2 or 3 independently selected substituents; and 
         R 1  is H; 
         wherein   represents the point of attachment to group M, * represents the point of attachment to group L and ** represents the point of attachment to group Y. 
       
     
     
         50 . The compound according to  claim 44 , wherein
 W is —═;   n is 0;   L is selected from the group consisting of aryl, —N(R 1 )C(O)-aryl, —CF 3 , heteroaryl, —N(R 1 )SO 2 -aryl, -alkynyl-aryl, -alkyl-aryl, —SO 2 —N(R 1 )—C 0 -C 4 -alkyl-aryl, —N(R 1 )-aryl, -heteroaryl-aryl, aryl-heteroaryl and fused heterocyclyl, wherein said aryl, heteroaryl and fused heterocyclyl are optionally substituted with 1, 2 or 3 independently selected substituents;   Y is selected from the group consisting of aryl, halo, heteroaryl and -heterocyclyl-C(O)-alkyl, wherein said aryl and heteroaryl are optionally substituted with 1, 2 or 3 independently selected substituents.   
     
     
         51 . The compound according to  claim 44 , wherein
 W is —C═;   n is 0;   L is selected from the group consisting of aryl, —N(R 1 )C(O)-aryl, —CF 3 , heteroaryl, —N(R 1 )SO 2 -aryl, -alkynyl-aryl, -alkyl-aryl, —SO 2 —N(R 1 )—C 0 -C 4 -alkyl-aryl, —N(R 1 )-aryl, -heteroaryl-aryl, aryl-heteroaryl and fused heterocyclyl, wherein said aryl, heteroaryl and fused heterocyclyl are optionally substituted with 1, 2 or 3 independently selected substituents;   Y is selected from the group consisting of aryl, halo, heteroaryl and -heterocyclyl-C(O)-alkyl, wherein said aryl and heteroaryl are optionally substituted with a substituent selected from the group consisting of alkyl, alkoxy and fused heterocyclyll.   
     
     
         52 . The compound according to  claim 44 , wherein
 W is —C═;   n is 0;   L is selected from the group consisting of phenyl, —N(R 1 )C(O)-aryl, —CF 3 , heteroaryl, —N(R 1 )—SO 2 -aryl, -alkynyl-aryl, -alkyl-aryl, —SO 2 —N(R 1 )—C 0 -C 4 -alkyl-aryl, —N(R 1 )-aryl, -heteroaryl-aryl, —S-aryl and fused heterocyclyl, wherein said aryl, heteroaryl and fused heterocyclyl are optionally substituted with 1, 2 or 3 independently selected substituents; and   Y is selected from the group consisting of aryl, halo, heteroaryl, —N(R 1 )—C(O)-alkyl-aryl, —C(O)—N(R 1 )-aryl-O-aryl, dibenzo[b,f][1,4]oxazepine, dibenzo[b,f][1,4]oxazepine-11-(10H)-one, —N(R 1 )—SO 2 -aryl, -alkyl-aryl, -alkyl-O-aryl, -aryl-heterocyclyl, benzo[d][1,3]dioxole, heterocyclyl, -heterocyclyl-alkyl-aryl, -heterocyclyl-C(O)-aryl, -2,3-dihydrobenzofuran, heterocyclyl-alkyl-heteroaryl, —CH-(aryl) 2 , -heterocyclyl-C(O)—O-alkyl, -heterocyclyl-SO 2 -alkyl, -heterocyclyl-SO 2 -aryl, -heterocyclyl-SO 2 -aryl-N(R 1 )—C(O)-alkyl, -alkyl-O—C(O)—N(R 1 )-alkyl-aryl, -alkyl-N(R 1 )-alkyl-aryl, —C(O)—N(R 1 )-aryl, —N(R 1 )—C(O)-alkyl-aryl, —N(R 1 )—SO 2 -aryl, —N(R 1 )—SO 2 -alkyl-aryl, —N(R 1 )—SO 2 -heteroaryl and -heterocyclyl-C(O)-alkyl, wherein said aryl and heteroaryl are optionally substituted with 1, 2 or 3 independently selected substituents.   
     
     
         53 . The compound according to  claim 44 , wherein 
       
         
           
           
               
               
           
         
          is selected from the group consisting of pyrazolyl, thiazolyl, thienyl, benzofuranyl, benzothienyl and pyrimidinyl; 
         W is —C═; 
         n is 0; 
         L is selected from the group consisting of phenyl, —N(R 1 )C(O)-aryl, —CF 3 , heteroaryl, —N(R 1 )—SO 2 -aryl, -alkynyl-aryl, -alkyl-aryl, —SO 2 —N(R 1 )—C 0 -C 4 -alkyl-aryl, —N(R 1 )-aryl, -heteroaryl-aryl, —S-aryl and fused heterocyclyl, wherein said aryl, heteroaryl and fused heterocyclyl are optionally substituted with 1, 2 or 3 independently selected substituents; and 
         Y is selected from the group consisting of aryl, halo, heteroaryl, —N(R 1 )—C(O)-alkyl-aryl, —C(O)—N(R 1 )-aryl-O-aryl, dibenzo[b,f][1,4]oxazepine, dibenzo[b,f][1,4]oxazepine-11-(10H)-one, —N(R 1 )—SO 2 -aryl, -alkyl-aryl, -alkyl-O-aryl, -aryl-heterocyclyl, benzo[d][1,3]dioxole, heterocyclyl, -heterocyclyl-alkyl-aryl, -heterocyclyl-C(O)-aryl, 2,3-dihydrobenzofuan, -heterocyclyl-alkyl-heteroaryl, —CH-(aryl) 2 , -heterocyclyl-C(O)—O-alkyl, -heterocyclyl-SO 2 -alkyl, -heterocyclyl-SO 2 -aryl, -heterocyclyl-SO 2 -aryl-N(R 1 )—C(O)-alkyl, -alkyl-O—C(O)—N(R 1 )-alkyl-aryl, -alkyl-N(R 1 )-alkyl-aryl, —C(O)—N(R 1 )-aryl, —N(R 1 )—C(O)-alkyl-aryl, —N(R 1 )—SO 2 -aryl, —N(R 1 )—SO 2 -alkyl-aryl, —N(R 1 )—SO 2 -heteroaryl and -heterocyclyl-C(O)-alkyl, wherein said aryl and heteroaryl are optionally substituted with 1, 2 or 3 independently selected substituents selected from the group consisting of alkyl, alkoxy, —CF 3 , optionally substituted phenyl, —N(R a )(R b ), —O-alkyl-morpholine and fused heterocyclyl. 
       
     
     
         54 . The compound according to  claim 44 , wherein 
       
         
           
           
               
               
           
         
          is selected from the group consisting of pyrazolyl, thiazolyl, thienyl, benzofuranyl, benzothienyl and pyrimidinyl; 
         W is —C═; 
         n is 0; 
         L is selected from the group consisting of phenyl, —N(R 1 )C(O)-phenyl, —CF 3 , benzothiazolyl, —N(R 1 )SO 2 -phenyl, -alkynyl-phenyl, thienyl, pyrrolyl, -alkyl-phenyl, pyridine, —SO 2 —N(R 1 )—C 0 -C 4 -alkyl-phenyl, —N(R 1 )-aryl, -thienyl-phenyl, —S-phenyl and fused heterocyclyl, wherein said phenyl, benzothiazolyl, thienyl, pyrrolyl, pyridine and fused heterocyclyl are optionally substituted with 1, 2 or 3 independently selected substituents; and 
         Y is selected from the group consisting of phenyl, halo, pyrrolyl, thienyl, —N(R 1 )—C(O)-alkyl-phenyl, —C(O)—N(R 1 )-phenyl-O-phenyl, dibenzo[b,f][1,4]oxazepine, dibenzo[b,f][1,4]oxazepine-11-(10H)-one, —N(R 1 )—SO 2 -phenyl, -alkyl-phenyl, -alkyl-O-phenyl, pyridinyl, -phenyl-morpholine, benzothiophene, benzo[d][1,3]dioxole, piperidinyl, -piperidine-alkyl-phenyl, -piperidine-C(O)-phenyl, 2,3-dihydrobenzofuran, -piperidine-alkyl-pyridine, —CH-(phenyl) 2 , -piperidine-C(O)—O-alkyl, -piperidine-SO 2 -alkyl, -piperidine-SO 2 -phenyl, -piperidine-alkyl-indole, -piperidine-SO 2 -phenyl-N(R 1 )—C(O)-alkyl, -alkyl-O—C(O)—N(R 1 )-alkyl-phenyl, -alkyl-N(R 1 )-alkyl-phenyl, —C(O)—N(R 1 )-phenyl, —N(R 1 )—C(O)-alkyl-phenyl, —N(R 1 )—SO 2 -phenyl, —N(R 1 )—SO 2 -alkyl-phenyl, —N(R 1 )—SO 2 -thienyl and -piperidine-C(O)-alkyl, wherein said phenyl, pyrrolyl, pyridinyl, benzothiophene, piperidinyl, indole and thienyl are optionally substituted with 1, 2 or 3 independently selected substituents. 
       
     
     
         55 . The compound according to  claim 44 , wherein 
       
         
           
           
               
               
           
         
          is selected from the group consisting of pyrazolyl, thiazolyl, thienyl, benzofuranyl, benzothienyl and pyrimidinyl; 
         W is —C═; 
         n is 0; 
         L is selected from the group consisting of phenyl, —N(R 1 )C(O)-phenyl, —CF 3 , benzothiazolyl, —N(R 1 )SO 2 -phenyl, -alkynyl-phenyl, thienyl, pyrrolyl, -alkyl-phenyl, pyridine, —SO 2 —N(R 1 )—C 0 -C 4 -alkyl-phenyl, —N(R 1 )-aryl, -thienyl-phenyl, —S-phenyl and fused heterocyclyl, wherein said phenyl, benzothiazolyl, thienyl, pyrrolyl, pyridine and fused heterocyclyl are optionally substituted with 1, 2 or 3 independently selected substituents; and 
         Y is selected from the group consisting of phenyl, halo, pyrrolyl, thienyl, —N(R 1 )—C(O)-alkyl-phenyl, —C(O)—N(R 1 )-phenyl-O-phenyl, dibenzo[b,f][1,4]oxazepine, dibenzo[b,f][1,4]oxazepine-11-(10H)-one, —N(R 1 )—SO 2 -phenyl, -alkyl-phenyl, -alkyl-O-phenyl, pyridinyl, -phenyl-morpholine, benzothiophene, benzo[d][1,3]dioxole, piperidinyl, -piperidine-alkyl-phenyl, -piperidine-C(O)-phenyl, 2,3-dihydrobenzofuan, -piperidine-alkyl-pyridine, —CH-(phenyl) 2 , -piperidine-C(O)—O-alkyl, -piperidine-SO 2 -alkyl, -piperidine-SO 2 -phenyl, -piperidine-alkyl-indole, -piperidine-SO 2 -phenyl-N(R 1 )—C(O)-alkyl, -alkyl-O—C(O)—N(R 1 )-alkyl-phenyl, -alkyl-N(R 1 )-alkyl-phenyl, —C(O)—N(R 1 )-phenyl, —N(R 1 )—C(O)-alkyl-phenyl, —N(R 1 )—SO 2 -phenyl, —N(R 1 )—SO 2 -alkyl-phenyl, —N(R 1 )—SO 2 -thienyl and -piperidine-C(O)-alkyl, wherein said phenyl, pyrrolyl, pyridinyl, benzothiophene, piperidinyl, indole and thienyl are optionally substituted with 1, 2 or 3 independently selected substituents selected from the group consisting of alkyl, alkoxy, —CF 3 , optionally substituted phenyl, —N(R a )(R b ), —O-alkyl-morpholine and fused heterocyclyl. 
       
     
     
         56 . The compound according to  claim 44 , having the Formula (In): 
       
         
           
           
               
               
           
         
         wherein 
         L is optionally substituted aryl; and 
         Y is aryl, —C 0 -C 3 alkyl-aryl or heteroaryl, wherein said aryl and heteroaryl moieties are optionally substituted with 1, 2 or 3 independently selected substituents. 
       
     
     
         57 . The compound according to  claim 44 , having the Formula (Iq): 
       
         
           
           
               
               
           
         
         wherein 
         L is optionally substituted aryl; and 
         Y is selected from the group consisting of aryl, aryl-heterocyclyl, heteroaryl, -heterocyclyl-C 0 -C 3 alkyl-aryl, —C 0 -C 3 alkyl-heterocyclyl, -heterocyclyl-C 0 -C 3 alkyl-heteroaryl, -heterocyclyl-C(O)-alkyl, and —CH(aryl) 2 , wherein each aryl, heterocyclyl and heteroaryl moiety is optionally substituted with 1 to 3 independently selected substituents, and each of which is optionally fused to one or more aryl, heterocyclic or heteroaryl rings, or one or more saturated or partially unsaturated cycloalkyl or heterocyclyl rings, each of which ring is optionally substituted with 1, 2 or 3 independently selected substituents. 
       
     
     
         58 . The compound according to  claim 44 , having the Formula (Iv): 
       
         
           
           
               
               
           
         
         wherein 
         L is optionally substituted phenyl; 
         Y is aryl, -alky-O-aryl, —C 0 -C 3 alkyl-aryl, -alkyl-O—C(O)—N(R 1 )-alkyl-aryl, -alkyl-N(R 1 )-alkyl-aryl and —C(O)—N(R 1 )-aryl, wherein each aryl moiety is optionally substituted with 1 to 3 independently selected substituents, and is optionally fused to one or more aryl, heterocyclic or heteroaryl rings, or one or more saturated or partially unsaturated cycloalkyl or heterocyclyl rings, each of which ring is optionally substituted; and 
         R 1  is selected from the group consisting of —H, -alkyl, -aryl, -aryl-aryl, -hetetoaryl, heteroaryl-aryl, heteroaryl-heteroaryl, alkyl-heteroaryl and -alkyl-aryl, wherein each aryl and heteroaryl moiety is optionally substituted. 
       
     
     
         59 . A compound of the Formula (II): 
       
         
           
           
               
               
           
         
         and N-oxides, hydrates, solvates, pharmaceutically acceptable salts, prodrugs and complexes thereof, and racemic and scalemic mixtures, tautomers, diastereomers and enantiomers thereof, wherein 
         L 2  is selected from the group consisting of
 H, —C 0 -C 3 alkyl-aryl, —C 0 -C 3 alkyl-heteroaryl, —C 1 -C 6 alkyl, in which each aryl and heteroaryl is optionally substituted with one, two or three substituents independently selected from halo, heterocyclyl, CF 3 , amino, OCH 3  and OH; and 
 
         Y is selected from the group consisting of H, halo, alkoxy, aryl, alkyl, heterocyclyl, heteroaryl, —N(R 1 )—C(O)-alkyl-aryl, —C(O)—N(R 1 )-aryl-O-aryl, —N(R 1 )—SO 2 -aryl, -alkyl-aryl, -alkyl-heteroaryl, -aryl-heterocyclyl, -heterocyclyl-alkyl-aryl, heterocyclyl-alkyl-heteroaryl, -heterocyclyl-C(O)-aryl, —CH(aryl) 2 , -heterocyclyl-C(O)-alkyl, -heterocyclyl-C(O)-heterocyclyl, -heterocyclyl-C(O)—O-alkyl, -heterocyclyl-SO 2 -alkyl, -heterocyclyl-SO 2 -aryl, -heterocyclyl-alkyl-heteroaryl, -heterocyclyl-SO 2 -aryl-N(R 1 )—C(O)-alkyl, -alkyl-O-aryl, -alkyl-O—C(O)—N(R 1 )-alkyl-aryl, -alkyl-N(R 1 )-alkyl-aryl, —C(O)—N(R 1 )-aryl, —N(R 1 )—C(O)—O-alkyl-aryl, —N(R 1 )—SO 2 -alkyl-aryl, —N(R 1 )—SO 2 -aryl and —N(R 1 )—SO 2 -heteroaryl, wherein each aryl, heteroaryl and heterocyclyl moiety is optionally substituted with 1 to 3 independently selected substituents, and each of which is optionally fused to one or more aryl, heterocyclic or heteroaryl rings, or one or more saturated or partially unsaturated cycloalkyl or heterocyclyl rings, each of which ring is optionally substituted; and 
         M is C(O)—NH—OH. 
       
     
     
         60 . A composition comprising a compound according to  claim 44  and a pharmaceutically acceptable carrier. 
     
     
         61 . A method of inhibiting HDAC activity, the method comprising contacting the HDAC or a cell comprising the HDAC with an inhibiting effective amount of a compound according to  claim 44  or a composition thereof. 
     
     
         62 . The method according to  claim 61 , wherein the HDAC is one or more of HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9 and HDAC11. 
     
     
         63 . A method of treating a disease responsive to an inhibitor of HDAC activity, comprising administering to an individual in need thereof an effective amount of a compound according to  claim 44  or a composition thereof. 
     
     
         64 . The method according to  claim 63 , wherein the disease is responsive to an inhibitor of one or more of HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9 and HDAC 11. 
     
     
         65 . A method of inhibiting HDAC activity, the method comprising contacting the HDAC or a cell comprising the HDAC with an inhibiting effective amount of a compound or an N-oxide, hydrate, solvate, pharmaceutically acceptable salt, prodrug or complex thereof, in the form of a racemic or scalemic mixture, tautomer, diastereomer or enantiomer thereof, or a composition of any of the foregoing, wherein the compound is selected from 
       
         
           
                 
                 
               
                     
                 
                   # 
                   Structure 
                 
                     
                 
                    66 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                    70 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                    71 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                    74 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                    80 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                    81 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                    86 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   106 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   108 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   109 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   110 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   111 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   112 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   113 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   114 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   117 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   120 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   122 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   125 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   130 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   132 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   133 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   139 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   140 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   142 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   144 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   145 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   147 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   148 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   150 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   151 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   152 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   153 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   156 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   158 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   164 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   180 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   181 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   182 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   183 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   201 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   202 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   203 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   204 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   205 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   206 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
                   207 
                   
                     
                       
                       
                           
                           
                       
                     
                   
                 
                     
                 
             
                
                
                
               
               
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         66 . The method according to  claim 65  wherein the HDAC is one or more of HDAC4, HDAC5, HDAC6, HDAC7, HDAC8, HDAC9 and HDAC11. 
     
     
         67 . A compound of the formula (I): 
       
         
           
           
               
               
           
         
         and or an N-oxide, hydrate, solvate, pharmaceutically acceptable salt, prodrug or complex thereof, in the form of a racemic or scalemic mixture, tautomer, diastereomer or enantiomer thereof, wherein 
       
       
         
           
           
               
               
           
         
          is pyrrole; 
         W is N or —C═; 
         M is C(O)N(H)OH; 
         R 1  and R 2  is independently selected from the group consisting of —H, -alkyl, -aryl, -aryl-aryl, -hetetoaryl, heteroaryl-aryl, heteroaryl-heteroaryl, alkyl-heteroaryl and -alkyl-aryl, wherein each aryl and heteroaryl moiety is optionally substituted; 
         R is selected from the group consisting of H, alkyl, halo, hydroxy, nitro, C 1 -C 4 alkyl, —NR′R 2 , —OR′, aryl, heteroaryl, alkyloxy and CF 3 ; 
         n is an integer from 0 to 1; 
         L is selected from the group consisting of aryl, heteroaryl, cycloalkyl, heterocyclyl, fused aryl, fused heterocyclyl, fused cycloalkyl, -alkenyl-aryl, -aryl-heteroaryl, -heteroaryl-aryl, -alkynyl-aryl, -alkyl-aryl, —SO 2 —N(R 1 )—C 0 -C 4 alkyl-aryl, —N(R 1 )-aryl, —CF 3 , -t-Bu, NR 1 SO 2 -aryl, halo, —N(R 1 )C(O)-aryl and —S-aryl, wherein each aryl, heteroaryl, cycloalkyl and heterocyclyl moiety is optionally substituted with 1 to 3 independently selected substituents, and each of which is optionally fused to one or more aryl, heterocyclic or heteroaryl rings, or one or more saturated or partially unsaturated cycloalkyl or heterocyclyl rings, each of which ring is optionally substituted, 
         wherein a heteroaryl moiety in 
       
       
         
           
           
               
               
           
         
          is optionally connected to a cycloalkyl, heterocyclyl, aryl or heteroaryl in L by a bond or by a bridging substituent; and 
         Y is selected from the group consisting of halo, alkoxy, aryl, heterocyclyl, heteroaryl, —N(R 1 )—C(O)-alkyl-aryl, —C(O)—N(R 1 )-aryl-O-aryl, —N(R 1 )—SO 2 -aryl, -alkyl-heteroaryl, -aryl-heterocyclyl, -heterocyclyl-alkyl-aryl, heterocyclyl-alkyl-heteroaryl, -heterocyclyl-C(O)-aryl, —CH(aryl) 2 , -heterocyclyl-C(O)-alkyl, -heterocyclyl-C(O)-heterocyclyl, -heterocyclyl-C(O)—O-alkyl, -heterocyclyl-SO 2 -alkyl, -heterocyclyl-SO 2 -aryl, -heterocyclyl-alkyl-heteroaryl, -heterocyclyl-SO 2 -aryl-N(R 1 )—C(O)-alkyl, -alkyl-O-aryl, -alkyl-O—C(O)—N(R 1 )-alkyl-aryl, -alkyl-N(R 1 )-alkyl-aryl, —C(O)—N(R 1 )-aryl, —N(R 1 )—C(O)—O-alkyl-aryl, —N(R 1 )—SO 2 -alkyl-aryl, —N(R 1 )—SO 2 -aryl and —N(R 1 )—SO 2 -heteroaryl, wherein each aryl, heteroaryl and heterocyclyl moiety is optionally substituted with 1 to 3 independently selected substituents, and each of which is optionally fused to one or more aryl, heterocyclic or heteroaryl rings, or one or more saturated or partially unsaturated cycloalkyl or heterocyclyl rings, each of which ring is optionally substituted.

Cited by (0)

No later patents cite this yet.

References (0)

No backward citations on record.