Substituted cyclic amine metalloprotease inhibitors

Abstract

The invention provides compounds which are useful as inhibitors of metalloproteases, and which are effective in treating conditions characterized by excess activity of these enzymes. In particular, the present invention relates to a compound having a structure according to Formula (I). Also disclosed are compounds, pharmaceutical compositions and methods of treating diseases characterized by metalloprotease activity using these compounds or the pharmaceutical compositions containing them.

1 - 28 . (canceled)  
     
     
         29 . A pharmaceutical composition comprising: 
 (a) a pharmaceutically-acceptable carrier;    (b) a safe and effective amount of a compound having a structure according to Formula (I):                          wherein:    A is alkyl, heteroalkyl, aryl or heteroaryl, substituted or unsubstituted;    R 1  is NHOR 2 , where R 2  is hydrogen or alkyl;    W is one or more of hydrogen; lower alkyl; or an alkylene bridge;    Y is independently one or more of hydroxy, SR 3 , SOR 4 , SO 2 R 8 , alkoxy, or amino, wherein amino is of formula NR 6 R 7 , wherein R 6  and R 7  are independently chosen from hydrogen, alkyl, heteroalkyl, heteroaryl, aryl, OR 3 , SO 2 R 8 , COR 9 , CSR 10 , and PO(R 11 ) 2 ; or R 6  and R 7  may join together to form a ring;    R 3  is hydrogen, alkyl, aryl, or heteroaryl;    R 4  is alkyl, aryl, or heteroaryl;    each R 8  is independently alkyl, aryl, heteroaryl, heteroalkyl, amino, alkylamino, dialkylamino, arylamino, diarylamino, or alkylarylamino;    R 9  is hydrogen, alkoxy, aryloxy, heteroaryloxy, alkyl, aryl, heteroaryl, heteroalkyl, amino, alkylamino, dialkylamino, arylamino, or alkylarylamino;    R 10  is alkyl, aryl, heteroaryl, heteroalkyl, amino, alkylamino, dialkylamino, arylamino, diarylamino, or alkylarylamino;    R 11  is alkyl, aryl, heteroaryl, or heteroalkyl;    Z is hydrogen; hydroxy; alkyl; or an alkylene, or heteroalkylene; and    n is 2;    or an optical isomer, diastereomer or enantiomer of Formula (I), or a pharmaceutically-acceptable salt, or biohydrolyzable amide, ester, or imide thereof.    
     
     
         30 . A composition according to  claim 29 , wherein said compound is selected from the group consisting of: 
 (2R)-N,4-dihydroxy-1-(4-methoxyphenylsulfonyl)piperidine-2-carboxamide;    (2R)-1-(4-bromophenylsulfonyl)-N,4-dihydroxypiperidine-2-carboxamide;    (2R)-N-hydroxy-1-(4-methoxyphenylsulfonyl)-4-(phenylthio)piperidine-2-carboxamide; and    (R)-N-hydroxy-4,4-dimethoxy-1-(4-methoxyphenylsulfonyl)piperidine-2-carboxamide.    
     
     
         31 . A composition according to  claim 29 , wherein said composition is formulated for an administration route selected from the group consisting of oral, rectal, topical, nasal, ocular, and parenteral.  
     
     
         32 . A composition according to  claim 29 , wherein said composition is formulated for oral administration, said formulation being a chewing gum.