Inhibitors of advanced glycation end products

Abstract

The present invention provides compounds of the formula, wherein A, B, G, R 2 , R 6 , and X are defined herein, pharmaceutical compositions of the same, and methods for treating or inhibiting development of AGE- and/or ALE-associated complications in subjects in need thereof

1 . A compound of the formula,  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt thereof, wherein 
 X is N, N—O, or CR 1 ;  
 G is —H, heterocycle, or —(C 1 -C 6 )alkyl, wherein the heterocycle and alkyl are optionally substituted with at least one group independently selected from the group consisting of -halogen, —OR G , —N(R G ) 2 , —SR G , —S(O)R G , —S(O) 2 R G , —COOR G , —CON(R G ) 2 , and —(C 1 -C 6 )alkyl-OR G , wherein R G  is hydrogen, —(C 1 -C 6 )alkyl, or —C(O)(C 1 -C 6 )alkyl;  
 A is of the formula,  
                     
 wherein  
 Y is N or N-oxide; and  
 ring C is:  
 (i) monocyclic;  
 (ii) saturated; and  
 (iii) contains 1 or 2 total heteroatoms, and 5 or 6 total atoms, wherein 
 the remaining heteroatom moiety is O, S, or NR N1 , and the carbon atoms are each optionally substituted with one or two R C  wherein 
 R N1  is —H, -oxide, —C 1 -C 6 )alkyl, —C 2 -C 6 )alkenyl, 
 —(C 1 -C 6 )alkynyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkanoyl, —(C 3 -C 8 )cycloalkyl, -heterocycle, -aryl, -heteroaryl, —(C 3 -C 8 )cycloalkanoyl, -heterocycloyl, -aroyl, -heteroaroyl, —(C 1 -C 6 )alkoxycarbonyl, or -aryl(C 1 -C 6 )alkoxycarbonyl, wherein 
 R N1  is optionally substituted with one or more groups which are independently -halogen, —OR N12 , —N(R N12 ) 2 , —COOR N12 , —CON(R N12 ) 2 , —SR N12 , —S(O)R N12 , —S(O) 2 R N12 , —NO 2 , —CN, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkyl-OR N12 , -aryl, —(C 1 C 6 )haloalkyl, —(C 3 -C 8 )cycloalkyl, —(C 1 -C 6 )alkanoyl, or -aroyl, wherein R N12  is hydrogen, —(C 1 -C 6 )alkyl, or —C(O)(C 1 -C 6 )alkyl;  
 
 
 
 
 each R C  is independently -Z 1 -M-Z 2 -R Z , wherein 
 M is —C(O)—, —C(S)—, —S(O)—, —S(O) 2 —, or absent, 
 provided when M is —S(O)—, —S(O)—, or absent, at least one of Z 1  and Z 2  is also absent;  
 
 Z 1  and Z 2  are independently —O—, —S—, —N(R N′ )—, or absent, wherein 
 R N′  is —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 1 -C 6 )alkynyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkanoyl, —(C 3 -C 8 )cycloalkyl, -heterocycle, -aryl, -heteroaryl, —(C 3 -C 8 )cycloalkanoyl, -heterocycloyl, -aroyl, -heteroaroyl, —(C 1 -C 6 )alkoxycarbonyl, or -aryl(C 1 -C 6 )alkoxycarbonyl, wherein 
 R N′  is optionally substituted with one or more groups which are independently -halogen, —OR, —COOR, —CONR 2 , —SR, —S(O)R, —S(O) 2 R, —NR 2 , —NO 2 , —CN, —(C 1 -C 6 )alkyl, -aryl, -heterocycle, -heteroaryl, —(C 3 -C 8 )cycloalkyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkanoyl, or -aroyl  
  wherein each R is independently —H, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkoxy, —(C 3 -C 8 )cycloalkyl, -heterocycloalkyl, aryl, or heteroaryl, wherein the alkyl and alkoxy are optionally substituted with one or more R′;  
  wherein each R′ is independently halogen, —OR″, —CN, —COR″, —COOR″, —CONR″ 2 , NR″ 2 , wherein  
  each R″ is independently —H, —(C 1 -C 6 )alkyl, or —(C 1 -C 6 )haloalkyl;  
 
 
 R Z  is —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 1 -C 6 )alkynyl, —(C 1 -C 6 )haloalkyl, —(C 3 -C 8 )cycloalkyl, —(C 1 -C 6 )alkylaryl, -heterocycle, -aryl, or -heteroaryl, wherein 
 R Z  is optionally substituted with at least one R Z′ , wherein 
 each R Z  is independently -halogen, —OR, —(C 1 -C 6 )alkoxy, —C(O)OR, —C(O)R, —C(O)NR 2 , —S(O) 2 R, —OS(O) 2 R, -cyano, -nitro,—(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 3 -C 8 )cycloalkyl, -heterocycloalkyl, or heteroaryl,  
  wherein R Z′  is optionally substituted with one or more R′,  
 
 
 
 or any two R C  attached to the same carbon, taken together, is oxo or ═N(R N4 ), wherein 
 R N4  is —H, —OR, —N(R N5 ) 2 , —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 1 -C 6 )alkynyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkanoyl, —(C 3 -C 8 )cycloalkyl, -heterocycle, -aryl, or -heteroaryl, wherein 
 R N4  is optionally substituted with one or more groups which are independently -halogen, —OH, -amino, —(C 1 -C 6 )alkylamino, —(C 1 -C 6 )dialkylamino, —NO 2 , —CN, —(C 1 -C 6 )alkyl, -aryl, -heteroaryl, -heterocycle, —(C 3 -C 8 )cycloalkyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkoxy, —(C 1 -C 6 )alkanoyl, or -aroyl; and  
 each R N5  is independently —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 1 -C 6 )alkynyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkanoyl, or —(C 3 -C 8 )cycloalkyl;  
 B is of the formula,  
                     
 wherein  
 
 
 ring D is (i) monocyclic, and 
 (ii) saturated, unsaturated, or aromatic;  
 
 R C′  is R C , provided that R C′  is not aryl or heteroaryl;  
 G 1 , G 2 , and G 3  each are independently N, O, CR 3 , C(R 3 ) 2 , or NR N′ , wherein 
 each R 3  is independently -Z 3 -M-Z 4 -R Z , 
 provided when M is —S(O)—, —S(O)—, or absent, at least one of Z 3  and Z 4  is also absent;  
 Z 3  and Z 4  are independently —O—, —S—, —N(R N3 )— or absent, wherein 
 R N3  is —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, —(C 1 -C 6 )alkynyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkanoyl, —(C 3 -C 8 )cycloalkanoyl, -heterocycloyl, -aroyl, -heteroaroyl, —(C 1 -C 6 )alkoxycarbonyl, or -aryl(C 1 -C 6 )alkoxycarbonyl, wherein 
 R N3  is optionally substituted with one or more groups which are independently -halogen, —OH, -amino, —(C 1 -C 6 )alkylamino, —(C 1 -C 6 )dialkylamino, —NO 2 , —CN, —(C 1 -C 6 )alkyl, -aryl, -heterocycle, -heteroaryl, —(C 3 -C 8 )cycloalkyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkoxy, —(C 1 -C 6 )alkanoyl, or -aroyl;  
 
 
 
 
 or two R 3  taken together are oxo; and  
 bonds a, b, c, d, and e are independently a single or double bond,  
 provided that 
 (i) no two consecutive atoms in ring D are both oxygen;  
 (ii) no two consecutive bonds are both double bonds;  
 (iii) if a or b is a double bond, then R C′  is absent; and  
 (iv) if a or e is a double bond, then R N′  is absent; and  
 
 R 1 , R 2 , and R 6  are independently —H, -halogen, —NO 2 , —CN, or R C ,  
 provided that when X═CR 1 , 
 (i) R 2 , R 6 , and R N1  are not phenyl;  
 (ii) R C  is not aryl, heteroaryl, heterocycle, or (C 2 -C 6 )alkenyl  
 (iii) and G 1 ═N together, then G 2  is not O; and  
 (iv) two R C  together may not form oxo;  
 
 and provided that when X═N, and 
 (i) G 1  and G 3 each are CR 3 , G 2 ═N, and bonds b and d are each a double bond, all simultaneously; or  
 (ii) G 1  is CR 3 , G 3  is C(O), G 2  is NR N′ , and bond b is a double bond, all simultaneously; either R 2  or R 6  is not —NH-aryl or —NH-heteroaryl.  
 
 
   
   
       2 . The compound according to  claim 1 , wherein X is N and G is hydrogen.  
   
   
       3 . The compound according to  claim 2 , wherein 
 B is aromatic; and    G 1 , G 2 , and G 3  are each independently O, N or CR 3 .    
   
   
       4 . The compound according to  claim 3 , wherein 
 B is imidazolyl, oxazoyl, pyrazoyl, pyrroyl, or isoxazoyl wherein each carbon atom is substituted by R 3 .    
   
   
       5 . The compound according to  claim 4 , wherein 
 B is imidazolyl wherein each carbon atom is substituted by R 3 .    
   
   
       6 . The compound according to  claim 5 , wherein 
 each R 3  is independently R Z3 , wherein 
 R Z3  is —H, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 3 -C 8 )cycloalkyl, —(C 1 -C 6 )alkylaryl, -heterocycle, -aryl, or -heteroaryl, wherein R Z3  is optionally substituted with at least one R Z3′ , wherein 
 each R Z3  is independently -halogen, -cyano, —OR, —C(O)OR, —C(O)R, —C(O)NR 2 , —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 3 -C 8 )cycloalkyl, or -heterocycloalkyl.  
 
   
   
   
       7 . The compound according to  claim 5 , wherein 
 R 2  and R 6  are each —H, -halogen, —NO 2 , —CN, or —R Z6  wherein 
 R Z6  is —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 3 -C 8 )cycloalkyl, —(C 1 -C 6 )alkylaryl, -heterocycle, -aryl, or -heteroaryl, wherein R Z6  is optionally substituted with at least one R Z6′ , 
 wherein each R Z6′  is independently -halogen, —OR, —C(O)OR, —C(O)R, —(C 1 -C 6 )alkyl, or —(C 1 -C 6 )haloalkyl, 
 wherein R Z6′  is optionally substituted with one or more R′.  
 
 
   
   
   
       8 . The compound according to  claim 5 , wherein 
 R N′  is —H, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkanoyl, —(C 3 -C 8 )cycloalkyl, -aryl, -heteroaryl, —(C 3 -C 8 )cycloalkanoyl, -heterocycloyl, -aroyl, -heteroaroyl, —(C 1 -C 6 )alkoxycarbonyl, or -aryl(C 1 -C 6 )alkoxycarbonyl, wherein 
 R N′  is optionally substituted with one or more groups which are independently -halogen, —OR N″ , —NR N″   2 , —NO 2 , —CN, —(C 1 -C 6 )alkyl, -aryl, -heterocycle, -heteroaryl, —(C 3 -C 8 )cycloalkyl, or —(C 1 -C 6 )haloalkyl, 
 wherein each R N″  is independently —H, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkoxy, —(C 3 -C 8 )cycloalkyl, -heterocycloalkyl, aryl, or heteroaryl, wherein the alkyl and alkoxy are optionally substituted with one or more R′.  
 
   
   
   
       9 . The compound according to  claim 5 , wherein 
 ring C contains 2 heteroatoms, and 5 total atoms, wherein the remaining heteroatom moiety is O, S, or NR N1 , and the carbon atoms are each optionally substituted with one or two R C .    
   
   
       10 . The compound according to  claim 5 , wherein 
 ring C contains 2 heteroatoms, and 6 total atoms, wherein    the remaining heteroatom moiety is O, S, or NR N1 , and the carbon atoms are each optionally substituted with one or two R C .    
   
   
       11 . The compound according to  claim 2 , wherein B is not aromatic and 
 G 1 , G 2 , and G 3  are each independently O, N, CR 3 ,C(R 3 ) 2 , or N(R N′ ).    
   
   
       12 . The compound according to  claim 12 , wherein 
 B is pyrrolidinyl, pyrazolidinyl, imidazolidinyl, isoxazolidinyl, oxazolidinyl, triazolidinyl, or tetrazolidinyl, wherein 
 each carbon is substituted by two R 3  and each nitrogen is substituted by R N′ .  
   
   
   
       13 . The compound according to  claim 12 , wherein 
 each R 3  is independently R Z3 , wherein 
 R Z3  is —H, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 3 -C 8 )cycloalkyl, —(C 1 -C 6 )alkylaryl, -heterocycle, -aryl, or -heteroaryl, wherein R Z3  is optionally substituted with at least one R Z3′ , wherein 
 each R Z3′  is independently -halogen, -cyano, —OR, —C(O)OR, —C(O)R, —C(O)NR 2 , —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 3 -C 8 )cycloalkyl, or -heterocycloalkyl.  
 
   
   
   
       14 . The compound according to  claim 12 , wherein 
 R 2  and R 6  are each —H, -halogen, —NO 2 , —CN, or —R Z6  wherein 
 R Z6  is —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 3 -C 8 )cycloalkyl, —(C 1 -C 6 )alkylaryl, -heterocycle, -aryl, or -heteroaryl, wherein R Z6  is optionally substituted with at least one R Z6′ , 
 wherein each R Z6′  is independently -halogen, —OR, —C(O)OR, —C(O)R, —(C 1 -C 6 )alkyl, or —(C 1 -C 6 )haloalkyl, 
 wherein R Z6′  is optionally substituted with one or more R′.  
 
 
   
   
   
       15 . The compound according to  claim 12 , wherein 
 each R N′  is —H, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkanoyl, —(C 3 -C 8 )cycloalkyl, -aryl, -heteroaryl, —(C 3 -C 8 )cycloalkanoyl, -heterocycloyl, -aroyl, -heteroaroyl, —(C 1 -C 6 )alkoxycarbonyl, or -aryl(C 1 -C 6 )alkoxycarbonyl, wherein 
 R N′  is optionally substituted with one or more groups which are independently -halogen, —OR N″ , —NR N″   2 , —NO 2 , —CN, —(C 1 -C 6 )alkyl, -aryl, -heterocycle, -heteroaryl, —(C 3 -C 8 )cycloalkyl, or —(C 1 -C 6 )haloalkyl, 
 wherein each R N″  is independently —H, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkoxy, —(C 3 -C 8 )cycloalkyl, -heterocycloalkyl, aryl, or heteroaryl, wherein the alkyl and alkoxy are optionally substituted with one or more R′.  
 
   
   
   
       16 . The compound according to  claim 12 , wherein 
 ring C contains 2 heteroatoms, and 5 total atoms, wherein    the remaining heteroatom moiety is O, S, or NR N1 , and the carbon atoms are each optionally substituted with one or two R C .    
   
   
       17 . The compound according to  claim 12 , wherein 
 ring C contains 2 heteroatoms, and 6 total atoms, wherein    the remaining heteroatom moiety is O, S, or NR N1 , and the carbon atoms are each optionally substituted with one or two R C .    
   
   
       18 . The compound according to  claim 1 , wherein X is CR 1  and G is hydrogen.  
   
   
       19 . The compound according to  claim 18 , wherein 
 R 1 is —N, —NO 2 , -halogen, —C(O)OR 4 , —C(O)R 4 , —C(O)N(R 4 ) 2 , —S(O)R 4 , —S(O) 2 R 4 , or —S(O) 2 N(R 4 ) 2 , wherein 
 each R 4 is independently —H, —(C 1 -C 6 )alkyl, —(C 2 -C 6 )alkenyl, 
 —(C 3 -C 8 )cycloalkyl, —(C 1 -C 6 )alkylaryl, -heterocycle, -aryl, or -heteroaryl, wherein 
 R 4  is optionally substituted with at least one group, each of which are independently -halogen, —OH, —(C 1 -C 6 )alkoxy, —C(O)R 41 , —S(O) 2 R 41 , —OS(O) 2 R 41 , -cyano, -nitro,—(C 1 -C 6 )alkyl, or —(C 1 -C 6 )haloalkyl,  
  wherein R 41  is —H, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkoxy, —(C 3 -C 8 )cycloalkyl, -heterocycloalkyl, aryl, or heteroaryl.  
 
 
   
   
   
       20 . The compound according to  claim 19 , wherein 
 B is aromatic; and    G 1 , G 2 , and G 3  are each independently O, N or CR 3 .    
   
   
       21 . The compound according to  claim 20 , wherein 
 B is imidazolyl, oxazoyl, pyrazoyl, pyrroyl, or isoxazoyl wherein each carbon atom is substituted by R 3 .    
   
   
       22 . The compound according to  claim 21 , wherein 
 B is imidazolyl wherein each carbon atom is substituted by R 3 .    
   
   
       23 . The compound according to  claim 22 , wherein 
 each R 3  is independently R Z3 , wherein 
 R Z3  is —H, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 3 -C 8 )cycloalkyl, —(C 1 -C 6 )alkylaryl, -heterocycle, -aryl, or -heteroaryl, wherein R Z3  is optionally substituted with at least one R Z3′ , wherein 
 each R Z3′  is independently -halogen, -cyano, —OR, —C(O)OR, —C(O)R, —C(O)NR 2 , —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 3 -C 8 )cycloalkyl, or -heterocycloalkyl.  
 
   
   
   
       24 . The compound according to  claim 22 , wherein 
 R 2  and R 6  are each —H, -halogen, —NO 2 , —CN, or —R Z6  wherein 
 R Z6  is —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 3 -C 8 )cycloalkyl, —(C 1 -C 6 )alkylaryl, -heterocycle, -aryl, or -heteroaryl, wherein R Z6  is optionally substituted with at least one R Z6′ , 
 wherein each R Z6′  is independently -halogen, —OR, —C(O)OR, —C(O)R, —(C 1 -C 6 )alkyl, or —(C 1 -C 6 )haloalkyl, 
 wherein R Z6′  is optionally substituted with one or more R′.  
 
 
   
   
   
       25 . The compound according to  claim 22 , wherein 
 R N′  is —H, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkanoyl, —(C 3 -C 8 )cycloalkyl, -aryl, -heteroaryl, —(C 3 -C 8 )cycloalkanoyl, -heterocycloyl, -aroyl, -heteroaroyl, —(C 1 -C 6 )alkoxycarbonyl, or -aryl(C 1 -C 6 )alkoxycarbonyl, wherein 
 R N′  is optionally substituted with one or more groups which are independently -halogen, —OR N″ , —NR N″   2 , —NO 2 , —CN, —(C 1 -C 6 )alkyl, -aryl, -heterocycle, -heteroaryl, —(C 3 -C 8 )cycloalkyl, or —(C 1 -C 6 )haloalkyl, 
 wherein each R N″  is independently —H, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkoxy, —(C 3 -C 8 )cycloalkyl, -heterocycloalkyl, aryl, or heteroaryl, wherein the alkyl and alkoxy are optionally substituted with one or more R′.  
 
   
   
   
       26 . The compound according to  claim 22 , wherein 
 ring C contains 2 heteroatoms, and 5 total atoms, wherein    the remaining heteroatom moiety is O, S, or NR N1 , and the carbon atoms are each optionally substituted with one or two R′.    
   
   
       27 . The compound according to  claim 22 , wherein 
 ring C contains 2 heteroatoms, and 6 total atoms, wherein    the remaining heteroatom moiety is O, S, or NR N1 , and the carbon atoms are each optionally substituted with one or two R C .    
   
   
       28 . The compound according to  claim 19 , wherein B is not aromatic and 
 G 1 , G 2 , and G 3  are each independently O, N, CR 3 ,C(R 3 ) 2 , or N(R N′ ).    
   
   
       29 . The compound according to  claim 28 , wherein 
 B is pyrrolidinyl, pyrazolidinyl, imidazolidinyl, isoxazolidinyl, oxazolidinyl, triazolidinyl, or tetrazolidinyl, wherein    each carbon is substituted by two R 3  and each nitrogen is substituted by R N′ .    
   
   
       30 . The compound according to  claim 29 , wherein 
 each R 3  is independently R Z3 , wherein 
 R Z3  is —H, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 3 -C 8 )cycloalkyl, —(C 1 -C 6 )alkylaryl, -heterocycle, -aryl, or -heteroaryl, wherein R Z3  is optionally substituted with at least one R Z3′ , wherein 
 each R Z3′  is independently -halogen, -cyano, —OR, —C(O)OR, —C(O)R, —C(O)NR 2 , —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 3 -C 8 )cycloalkyl, or -heterocycloalkyl.  
 
   
   
   
       31 . The compound according to  claim 29 , wherein 
 R 2  and R 6  are each —H, -halogen, —NO 2 , —CN, or —R Z6  wherein 
 R Z6  is —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 3 -C 8 )cycloalkyl, —(C 1 -C 6 )alkylaryl, -heterocycle, -aryl, or -heteroaryl, wherein R Z6  is optionally substituted with at least one R Z6′ , 
 wherein each R Z6′  is independently -halogen, —OR, —C(O)OR, —C(O)R, —(C 1 -C 6 )alkyl, or —(C 1 -C 6 )haloalkyl, 
 wherein R Z6′  is optionally substituted with one or more R′.  
 
 
   
   
   
       32 . The compound according to  claim 29 , wherein 
 each R N′  is independently —H, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkanoyl, —(C 3 -C 8 )cycloalkyl, -aryl, -heteroaryl, —(C 3 -C 8 )cycloalkanoyl, -heterocycloyl, -aroyl, -heteroaroyl, —(C 1 -C 6 )alkoxycarbonyl, or -aryl(C 1 -C 6 )alkoxycarbonyl, wherein 
 R N′  is optionally substituted with one or more groups which are independently -halogen, —OR N″ , —NR N″   2 , —NO 2 , —CN, —(C 1 -C 6 )alkyl, -aryl, -heterocycle, -heteroaryl, —(C 3 -C 8 )cycloalkyl, or —(C 1 -C 6 )haloalkyl, 
 wherein each R N″  is independently —, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )haloalkyl, —(C 1 -C 6 )alkoxy, —(C 3 -C 8 )cycloalkyl, -heterocycloalkyl, aryl, or heteroaryl, wherein the alkyl and alkoxy are optionally substituted with one or more R′.  
 
   
   
   
       33 . The compound according to  claim 29 , wherein 
 ring C contains 2 heteroatoms, and 5 total atoms, wherein    the remaining heteroatom moiety is O, S, or NR N1 , and the carbon atoms are each optionally substituted with one or two R C .    
   
   
       34 . The compound according to  claim 29 , wherein 
 ring C contains 2 heteroatoms, and 6 total atoms, wherein    the remaining heteroatom moiety is O, S, or NR N1 , and the carbon atoms are each optionally substituted with one or two R C .    
   
   
       35 . The compound according to  claim 1  which is 
 4-(1H-imidazol-2-yl)-2-methyl-5-((4-methylpiperazin-1-yl)methyl)pyridin-3-ol.    
   
   
       36 . A pharmaceutical composition comprising the compound of  claim 1  and a pharmaceutically acceptable carrier.  
   
   
       37 . A method for treating or inhibiting development of one or more AGE- and/or ALE-associated complications in subject in need thereof comprising administering one or more compounds according to  claim 1  to the subject.  
   
   
       38 . A method for treating or inhibiting development of one or more AGE- and/or ALE-associated complications in a subject in need thereof comprising administering one or more pharmaceutical compositions according to  claim 26  to the subject.  
   
   
       39 . The method of  claim 37  wherein the one or more AGE- and/or ALE-associated complications are selected from the group consisting of accelerated protein aging, retinopathy, nephropathy, proteinuria, impaired glomerular clearance, neuropathy, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, atherosclerosis, cardiovascular disease, neurodegenerative amyloid diseases, diabetes-associated hyperlipidemia, oxidative modification of proteins, arthritis, connective tissue diseases, amyloidosis, urinary stone disease, obesity-related complications, proliferation of smooth muscle cells in the aorta, coronary artery occlusion, hypertension; and dialysis-related disorders selected from the group consisting of dialysis-related cardiac morbidity and mortality, dialysis-related amyloidosis, dialysis-related increases in permeability of the peritoneal membrane in a dialysis patient, renal failure progression in a dialysis patient, and ultrafiltration failure and peritoneal membrane destruction in a dialysis patient.  
   
   
       40 . A method for treating or inhibiting development of one or more disorders selected from the group consisting of diabetic nephropathy, proteinuria, impaired glomerular clearance, retinopathy, neuropathy, atherosclerosis, diabetes-associated hyperlipidemia, oxidative modification of proteins, arthritis, connective tissue diseases, amyloidosis, urinary stone disease, obesity-related complications proliferation or smooth muscle cells in the aorta, coronary artery occlusion, and hypertension; and dialysis-related disorders including dialysis-related cardiac morbidity and mortality, dialysis-related amyloidosis, dialysis-related increases in permeability of the peritoneal membrane in a dialysis patient, renal failure progression in a dialysis patient, and inhibiting ultrafiltration failure and peritoneal membrane destruction in a dialysis patient, wherein the method comprises administering an effective amount of a compound according to  claim 1  to a subject in need of such treatment.  
   
   
       41 . A method for treating or inhibiting development of one or more disorders selected from the group consisting of diabetic nephropathy, proteinuria, impaired glomerular clearance, retinopathy, neuropathy, atherosclerosis, diabetes-associated hyperlipidemia, oxidative modification of proteins, arthritis, connective tissue diseases, amyloidosis, urinary stone disease, obesity-related complications proliferation or smooth muscle cells in the aorta, coronary artery occlusion, and hypertension; and dialysis-related disorders including dialysis-related cardiac morbidity and mortality, dialysis-related amyloidosis, dialysis-related increases in permeability of the peritoneal membrane in a dialysis patient, renal failure progression in a dialysis patient, and inhibiting ultrafiltration failure and peritoneal membrane destruction in a dialysis patient, wherein the method comprises administering an effective amount of a pharmaceutical composition according to  claim 36  to a subject in need of such treatment.