Hydroxamic and carboxylic acid derivatives

Abstract

The invention relates to hydroxamic and carboxylic acid derivatives. Compounds of the formula: are disclosed. These compounds are useful for the treatment of diseases mediated by inhibitors of matrix metalloproteinase, ADAM, ADAM-TS enzymes, and/or TNFα-mediated diseases including degenerative diseases and certain cancers.

We claim:  
     
         1 . A compound of formula (I)  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is the OH or NHOH;  
 R 2  is H, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclo or heterocycloalkyl (any of which may be optionally substituted with one or more substituents selected from R 6 , W and WR 6 ); and  
 R 3  is H or alkyl;  
 or R 2 , R 3  and the carbon atom to which they are attached together represent a carbocyclic or heterocyclic ring (either of which may be substituted with one or more substituents selected from R 6 , W and WR 6 );  
 R 4  is alkyl, cycloalkyl, OR 9 , CO 2 R 14 , COR 10 , S(O) q R 10  where q is 0, 1 or 2, CONR 7 R 8 , CN or S(O) q NR 7 R 8 , two R 4  substituents may be attached to the same carbon atom to form C(R 4 ) 2 , where each R 4  is the same or different, or C(R 4 ) 2  may represent C═O;  
 R 5  is alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, CF 3 , OR 9 , CO 2 R 10 , S(O) q R 10 , CO 2 R 14 , CONR 7 R 8 , S(O) q NR 7 R 8 , halogen, NR 10 R 11  or CN, or two adjacent R 5  substituents may be combined to form a heterocyclic ring;  
 R 6  is OR 9 , COR 10 , CO 2 R 15 , CONR 7 R 8 , NR 10 R 11 , S(O) q R 10 , S(O) q NR 7 R 8 , ═O, ═NOR 10 , succinimido or the group  
                     
 R 7  and R 8 , which may the same or different, are each H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl, or R 7  and R 8  and the nitrogen to which they are attached together represent a heterocyclic ring;  
 R 9  is H, alkyl, CF 3 , CHF 2 , CH 2 F, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;  
 R 10  is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl; and  
 R 11  is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl, cycloalkylalkyl, COR 12 , CONR 7 R 8 , S(O) q R 12  or S(O) q NR 7 R 8 ;  
 or R 10  and R 11  and the nitrogen to which they are attached together represent a heterocyclic ring;  
 R 12  is OR 9  or R 13 ;  
 R 13  is alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;  
 R 14  is H, alkyl or cycloalkyl;  
 R 15  is H, alkyl, cycloalkyl, arylalkyl or heteroarylalkyl;  
 X is a bond (i.e. is absent), —O—, —C(O)—, —S(O) q —, —N(R 11 )—, —N(R 11 )C(R 16 ) 2 —, —S(O) q C(R 16 ) 2 —, —C(R 6 ) 2 N(R 1  I)_, C(R 16 ) 2 S(O) q —, —C(R 16 )═N—, —N═C(R 16 )—, —N(R 11 )SO 2 —, —SO 2 N(R 11 )—, —N(R 11 )CO— or —CON(R 11 )—; and the R 16  groups in C(R 16 ) 2  may be the same or different;  
 Y is a bond (i.e. is absent), —O—, —C(O)—, —S(O) q —, —N(R 11 )—, —N(R 11 )C(R 16 ) 2 —, —S(O) q C(R 16 ) 2 —, —C(R 16 ) 2 N(R 11 )—, C(R 16 ) 2 S(O) q —, —C(R 16 )═N—, —N═C(R 16 )_, N(R 11   1 )SO 2 —, SO 2 N(R 11 )—, —N(R 11 )CO— or —CON(R 11 )—; and the R 16  groups in C(R 16 ) 2  may be the same or different;  
 R 16  is H, alkyl, cycloalkyl, OR 9 , CO 2 R 14 , COR 10 , S(O) q R 10 , CONR 7 R 8 , CN or S(O) q NR 7 R 8 ;  
 R 17  is H or alkyl;  
 W is alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclo or heterocycloalkyl;  
   represents a single or double bond;  
 each k and m is independently 0, 1, 2 or 3;  
 n is 0, 1 or 2; and  
 p is 0, 1 or 2, provided that n+p does not exceed 3;  
 or a salt, solvate, hydrate, N-oxide, protected amino, protected carboxy or protected hydroxamic acid thereof.  
 
     
     
         2 . The compound of  claim 1 , wherein R 1  is NHOH.  
     
     
         3 . The compound of  claim 1 , wherein p is 1; R 4  is alkyl, cycloalkyl, OR 9 , CO 2 R 14 , COR 10 , S(O) q R 10 , CONR 7 R 8 , CN or, S(O) q NR 7 R 8 , or C(R 4 ) 2  may represent C═O; R 6  is not succinimido or the said group; when R 6  is CO 2 R 15 , R 15  is H, alkyl or cycloalkyl; and n is 1 or 2.  
     
     
         4 . The compound of  claim 1 , which is selected from 
 3-methyl-2-(1,3,4,9-tetrahydro-β-carboline-2-sulfonylmethyl)butyric acid, 2-(6-methoxy-1,3,4,9-tetrahydro-β-carboline-2-sulfonylmethyl)-3-methylbutyric acid, 2-(3,4-dihydro-1H-benzo[4,5]furo[2,3-c]pyridine-2-sulfonylmethyl)-3-methylbutyric acid, N-hydroxy-3-methyl-2-(1,3,4,9-tetrahydro-β-carboline-2-sulfonylmethyl)-butyramide, 2-(3,4-dihydro-1H-benzo[4,5]furo[2,3-c]pyridine-2-sulfonylmethyl-N-hydroxy-3-methylbutyramide, and N-hydroxy-2-(6-methoxy-1,3,4,9-tetrahydro-β-carboline-2-sulfonylmethyl)-3-methylbutyramide.    
     
     
         5 . The compound of  claim 1 , which is selected from 2-[2-(1-benzyloxycarbonylpiperidin-4-yl)-2-carboxyethanesulfonyl]-1,2,3,4-tetrahydro-β-carboline-9-carboxylic acid 2,2,2-trichloroethyl ester, 4-(1,3,4,9-tetrahydro-β-carboline-2-sulfonylmethyl)-tetrahydropyran-4-carboxylic acid, 2-(R)-(3,4-dihydro-1H-benzo [4,5]thieno [2,3-c]pyridine-2-sulfonylmethyl-3-methylbutyric acid, 4-(3,4-dihydro-1H-benzo[4,5]thieno[2,3-c]pyridine-2-sulfonylmethyl)-tetrahydropyran-4-carboxylic acid, 2-[2-(1-benzyloxycarbonyl-piperidin-4-yl)-2-hydroxy carbamoylethanesulfonyl]-1,2,3,4-tetrahydro-β-carboline-9-carboxylic acid 2,2,2-trichloroethyl ester, (1,3,4,9-tetrahydro-β-carboline-2-sulfonyhnethyl)tetrahydropyran-4-carboxylic acid hydroxamide, 2-(R)-(3,4-dihydro-1H-benzo[4,5]thieno[2,3-c]pyridine-2-sulfonyhnethyl-N-hydroxy-3-methylbutyramide, 4-(3,4-dihydro-1H-benzo[4,5]thieno[2,3-c]pyridine-2-sulfonylmethyl)-tetrahydropyran-4-carboxylic acid hydroxamide, and 4-[1-hydroxycarbamoyl-2-(1,3,4,9-tetrahydro-β-carboline-2-sulfonyl)ethyl]-piperidine-1-carboxylic acid benzyl ester.  
     
     
         6 . A pharmaceutical composition for use in therapy, comprising a compound of formula (I)  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is the OH or NHOH;  
 R 2  is H, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclo or heterocycloalkyl (any of which may be optionally substituted with one or more substituents selected from R 6 , W and WR6); and  
 R 3  is H or alkyl;  
 or R 2 , R 3  and the carbon atom to which they are attached together represent a carbocyclic or heterocyclic ring (either of which may be substituted with one or more substituents selected from R 6 , W and WR6);  
 R 4  is alkyl, cycloalkyl, OR 9 , CO 2 R 14 , COR 10 , S(O) q R 10  where q is 0, 1 or 2, CONR 7 R 8 , CN or S(O) q NR 7 R 8 ; two R 4  substituents may be attached to the same carbon atom to form C(R 4 ) 2 , where each R 4  is the same or different, or C(R 4 ) 2  may represent C═O;  
 R 5  is alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, CF 3 , OR 9 , COR 10 , S(O) q R 10 , CO 2 R 4 , CONR 7 R 8 , S(O) q NR 7 R 8 , halogen, NR 10 R 11  or CN, or two adjacent R 5  substituents may be combined to form a heterocyclic ring;  
 R 6  is OR 9 , COR10, CO 2 R 15 , CONR 7 R 8 , NR 10 R 11 , S(O) q R 10 , S(O) q NR 7 R 8 , ═O, ═NOR 10 , succinimido or the group  
                     
 R 7  and R 8 , which may the same or different, are each H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl, or R 7  and R 8  and the nitrogen to which they are attached together represent a heterocyclic ring;  
 R 9  is H, alkyl, CF 3 , CHF 2 , CH 2 F, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;  
 R 9  is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl; and  
 R 11  is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl, cycloalkylalkyl, COR 12 , CONR 7 R 8 , S(O) q R 12  or S(O) q NR 7 R 8 ;  
 or R 10  and R 11  and the nitrogen to which they are attached together represent a heterocyclic ring;  
 R 12  is OR 9  or R 13 ;  
 R 13  is alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;  
 R 14  is H, alkyl or cycloalkyl;  
 R 15  is H, alkyl, cycloalkyl, arylalkyl or heteroarylalkyl;  
 X is a bond (i.e. is absent), —O—, —C(O)—, —S(O) q —, —N(R 11 )—, —N(R 1 )C(R 16 ) 2 —, —S(O) q C(R 16 ) 2 —, C(R 16 ) 2 N(R 11 )—, C(R 16 ) 2 S(O) q —, —C(R 6 )═N—, —N═C(R 16 )—, —N(R 11 )SO 2 —, —SO 2 N(R 11 )—, —N(R 11 )CO— or —CON(R 11 )—; and the R 16  groups in C(R 16 ) 2  may be the same or different;  
 Y is a bond (i.e. is absent), —O—, —C(O)—, —S(O) q —, —N(R 11 )—, —N(R 11 )C(R 16 ) 2 —, —S(O) q C(R 16 ) 2 —, —C(R 16 ) 2 N(R 11 )—, —C(R 16 ) 2 S(O) q —, —C(R 116 )═N—, —N═C(R 16 )—, N(R 11 )SO 2 —, SO 2 N(R 11 )—, —N(R 11 )CO— or —CON(R 11 )—; and the R 16  groups in C(R 16 ) 2  may be the same or different;  
 R 16  is H, alkyl, cycloalkyl, OR 9 , CO 2 R 14 , COR10, S(O) q R 10 , CONR 7 R 8 , CN or S(O) q NR 7 R 8 ;  
 R 17  is H or alkyl;  
 W is alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclo or heterocycloalkyl; =represents a single or double bond;  
 each k and m is independently 0, 1, 2 or 3;  
 n is 0, 1 or 2; and  
 p is 0, 1 or 2, provided that n+p does not exceed 3;  
 or a salt, solvate, hydrate, N-oxide, protected amino, protected carboxy or protected hydroxamic acid thereof; and a pharmaceutically-acceptable diluent or carrier.  
 
     
     
         7 . The composition of  claim 6 , wherein wherein R 1  is NHOH.  
     
     
         8 . The composition of  claim 6 , wherein p is 1; R 4  is alkyl, cycloalkyl, OR 9 , CO 2 R 14 , COR10, S(O) q R 10 , CONR 7 R 8 , CN or, S(O) q NR 7 R 8 , or C(R 4 ) 2  may represent C═O; R 6  is not succinimido or the said group; when R 6  is CO 2 R 15 , R 15  is H, alkyl or cycloalkyl; and n is 1 or 2.  
     
     
         9 . The composition of  claim 6 , wherein said compound is selected from 3-methyl-2-(1,3,4,9-tetrahydro-β-carboline-2-sulfonylmethyl)butyric acid, 2-(6-methoxy-1,3,4,9-tetrahydro-β-carboline-2sulfonylmethyl)-3-methylbutyric acid, 2-(3,4-dihydro-1H-benzo[4,5]furo[2,3-c]pyridine-2-sulfonylmethyl)-3-methylbutyric acid, N-hydroxy-3-methyl-2-(1,3,4,9-tetrahydro-β-carboline-2-sulfonylmethyl)-butyramide, 2-(3,4-dihydro-1H-benzo[4,5] furo[2,3-c]pyridine-2-sulfonylmethyl-N-hydroxy-3-methylbutyramide, and N-hydroxy-2-(6-methoxy-1,3,4,9-tetrahydro-β-carboline-2-sulfonylmethyl)-3-methylbutyramide.  
     
     
         10 . The composition of  claim 6 , wherein said compound is selected from 2-[2-(1-benzyloxycarbonylpiperidin-4-yl)-2-carboxyethanesulfonyl]-1,2,3,4-tetrahydro-β-carboline-9-carboxylic acid 2,2,2-trichloroethyl ester, 4-(1,3,4,9-tetrahydro-β-carboline-2-sulfonylmethyl)-tetrahydropyran-4-carboxylic acid, 2-(R)-(3,4-dihydro-1H-benzo[4,5]thieno[2,3-c]pyridine-2-sulfonylmethyl-3-methylbutyric acid, 4-(3,4-dihydro-1H-benzo[4,5]thieno[2,3-c]pyridine-2-sulfonylmethyl)-tetrahydropyran-4-carboxylic acid, 2-[2-(1-benzyloxycarbonyl-piperidin-4-yl)-2-hydroxy carbamoylethanesulfonyl]-1,2,3,4-tetrahydro-β-carboline-9-carboxylic acid 2,2,2-trichloroethyl ester, (1,3,4,9-tetrahydro-β-carboline-2-sulfonylmethyl)tetrahydropyran-4-carboxylic acid hydroxamide, 2-(R)-(3,4-dihydro-1H-benzo[4,5]thieno[2,3-c]pyridine-2-sulfonylmethyl-N-hydroxy-3-methylbutyramide, 4-(3,4-dihydro-1H-benzo[4,5]thieno[2,3-c]pyridine-2-sulfonylmethyl)-tetrahydropyran-4-carboxylic acid hydroxamide, and 4-[1-hydroxycarbamoyl-2-(1,3,4,9-tetrahydro-β-carboline-2-sulfonyl)ethyl]-piperidine-1-carboxylic acid benzyl ester.  
     
     
         11 . A method for the treatment of cancer; inflamation; or an autoimmune, infectious or ocular disease; wherein said method comprises administering to a patient in need of such treatment an effective amount of a compound of formula (I)  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is the OH or NHOH;  
 R 2  is H, alkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl, heterocyclo or heterocycloalkyl (any of which may be optionally substituted with one or more substituents selected from R 6 , W and WR6); and  
 R 3  is H or alkyl;  
 or R 2 , R 3  and the carbon atom to which they are attached together represent a carbocyclic or, heterocyclic ring (either of which may be substituted with one or more substituents selected from R 6 , W and WR6);  
 R 4  is alkyl, cycloalkyl, OR 9 , CO 2 R 14 , COR 11 , S(O) q R 10  where q is 0, 1 or 2, CONR 7 R 8 , CN or S(O) q NR 7 R 8 ; two R 4  substituents may be attached to the same carbon atom to form C(R 4 ) 2 , where each R 4  is the same or different, or C(R 4 ) 2  may represent C═O;  
 R 5  is alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, CF 3 , OR 9 , COR10, S(O) q R 11 , CO 2 R 14 , CONR 7 R 8 , S(O) q NR 7 R 8 , halogen, NR 10 R 11  or CN, or two adjacent R 5  substituents may be combined to form a heterocyclic ring;  
 R 6  is OR 9 , COR10, CO 2 R 15 , CONR 7 R 8 , NRIOR 11 , S(O) q R 10 , S(O) q NR 7 R 8 , ═O, ═NOR 10 , succinimido or the group  
                     
 R 7  and R 8 , which may the same or different, are each H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl, or R 7  and R 8  and the nitrogen to which they are attached together represent a heterocyclic ring;  
 R 9  is H, alkyl, CF 3 , CHF 2 , CH 2 F, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;  
 R 10  is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl; and  
 R 11  is H, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl, cycloalkylalkyl, COR 12 , CONR 7 R 8 , S(O) q R 12  or S(O) q NR 7 R 8 ;  
 or R 10  and R 11  and the nitrogen to which they are attached together represent a heterocyclic ring;  
 R 12  is OR 9  or R 13 ;  
 R 13  is alkyl, cycloalkyl, aryl, heteroaryl, heterocyclo, arylalkyl, heteroarylalkyl, heterocycloalkyl or cycloalkylalkyl;  
 R 14  is H, alkyl or cycloalkyl;  
 R 15  is H, alkyl, cycloalkyl, arylalkyl or heteroarylalkyl;  
 X is a bond (i.e. is absent), —O—, —C(O)—, —S(O) q —, —N(R 11 )—, —N(R 11 )C(R 16 ) 2 —, —S(O) q C(R 16 ) 2 —, —C(R 16 ) 2 N(R 11 )—, C(R 16 ) 2 S(O) q —, —C(R 16 )═N—, —N═C(R 16 )_, —N(R 11 )SO 2 —, —SO 2 N(R 11 )—, —N(R 11 )CO— or —CON(R 11 )—; and the R 16  groups in C(R 16 ) 2  may be the same or different;  
 Y is a bond (i.e. is absent), —O—, —C(O)—, —S(O) q —, —N(R 11 )—, —N(R 11 )C(R 16 ) 2 —, —S(O) q C(R 16 ) 2 —, —C(R   16 ) 2 N(R 11 )—, —C(R 16 ) 2 S(O) q —, —C(R 16 )═N—, —N═C(R 16 )—, N(R 11 )SO 2 —,  
 SO 2 N(R 11 )—, —N(R 11 )CO— or —CON(R 11 )—; and the R 16  groups in C(R 16 ) 2  may be the same or different;  
 R 16  is H, alkyl, cycloalkyl, OR 9 , CO 2 R 14 , COR10, S(O) q R 10 , CONR 7 R 8 , CN or S(O) q NR 7 R 8 ;  
 R 17  is H or alkyl;  
 W is alkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclo or heterocycloalkyl;  
   represents a single or double bond;  
 each k and m is independently 0, 1, 2 or 3;  
 n is 0, 1 or 2; and  
 p is 0, 1 or 2, provided that n+p does not exceed 3;  
 or a salt, solvate, hydrate, N-oxide, protected amino, protected carboxy or protected hydroxamic acid thereof.  
 
     
     
         12 . The method of  claim 11 , wherein wherein R 1  is NHOH.  
     
     
         13 . The method of  claim 11 , wherein p is 1; R 4  is alkyl, cycloalkyl, OR 9 , CO 2 R 14 , COR 10 , S(O) q R 10 , CONR 7 R 8 , CN or, S(O) q NR 7 R 8 , or C(R 4 ) 2  may represent C═O; R 6  is not succinimido or the said group; when R 6  is CO 2 R 15 , R 15  is H, alkyl or cycloalkyl; and n is 1 or 2.  
     
     
         14 . The method of  claim 11 , wherein said compound is selected from 3-methyl-2-(1,3,4,9-tetrahydro-β-carboline-2-sulfonylmethyl)butyric acid, 2-(6-methoxy-1,3,4,9-tetrahydro-β-carboline-2-sulfonylmethyl)-3-methylbutyric acid, 2-(3,4-dihydro-1H-benzo[4,5]furo[2,3-c]pyridine-2-sulfonylmethyl)-3-methylbutyric acid, N-hydroxy-3-methyl-2-(1,3,4,9-tetrahydro-β-carboline-2-sulfonylmethyl)-butyramide, 2-(3,4-dihydro-1H-benzo[4,5]furo[2,3-c]pyridine-2-sulfonylmethyl-N-hydroxy-3-methylbutyramide, and N-hydroxy-2-(6-methoxy-1,3,4,9-tetrahydro-β-carboline-2-sulfonylmethyl)-3-methylbutyramide.  
     
     
         15 . The method of  claim 11 , wherein said compound is selected from 2-[2-(1-benzyloxycarbonylpiperidin-4-yl)-2-carboxyethanesulfonyl]-1,2,3,4-tetrahydro-β-carboline-9-carboxylic acid 2,2,2-trichloroethyl ester, 4-(1,3,4,9-tetrahydro-β-carboline-2-sulfonylmethyl)-tetrahydropyran-4-carboxylic acid, 2-(R)-(3,4-dihydro-1H-benzo[4,5]thieno[2,3-c]pyridine-2-sulfonylmethyl-3-methylbutyric acid, 4-(3,4-dihydro-1H-benzo[4,5]thieno[2,3-c]pyridine-2-sulfonylmethyl)-tetrahydropyran-4-carboxylic acid, 2-[2-(1-benzyloxycarbonyl-piperidin-4-yl)-2-hydroxy carbamoylethanesulfonyl]-1,2,3,4-tetrahydro-β-carboline-9-carboxylic acid 2,2,2-trichloroethyl ester, (1,3,4,9-tetrahydro-β-carboline-2-sulfonylmethyl)tetrahydropyran-4-carboxylic acid hydroxamide, 2-(R)-(3,4-dihydro-1H-benzo[4,5]thieno[2,3-c]pyridine-2-sulfonylmethyl-N-hydroxy-3-methylbutyramide, 4-(3,4-dihydro-1H-benzo[4,5]thieno[2,3-c]pyridine-2-sulfonylmethyl)-tetrahydropyran-4-carboxylic acid hydroxamide, and 4-[1-hydroxycarbamoyl-2-(1,3,4,9-tetrahydro-β-carboline-2-sulfonyl)ethyl]-piperidine-1-carboxylic acid benzyl ester.