Half-sandwich ruthenium (II) compounds comprising nitrogen containing ligands for treatment of cancer

Abstract

Compounds which may be used in the treatment and/or prevention of cancer have the formula (I) wherein: R 1 , R 2 , R 3 , R 4 , R 5 and R 6 independently represents H, alkyl, —CO 2 R′, aryl or akylaryl, which latter two groups are optionally substituted on the aromatic ring; R′ represent alkyl, aryl or alkaryl; X is halo, H 2 O, (R′)(R″)SO, R′CO 2 — or (R′)(R″)C═O, where R″ represents alkyl, aryl or alkaryl; Y is a counterion; m is 0 or 1; q is 1, 2 or 3; C′ is C 1 to C 12 alkylene, optionally substituted in or on the alkylene chain, bound to two A groups; p is 0 or 1 and r is 1 when p is 0 and r is 2 when p is 1, and A and B are: each independently N-donor nitrile ligands; or B is halo and A is an N-donor pyridine ligand, optionally substituted at one or more of the carbon atoms of the pyridine ring; or p is 0, A is NR 7 R 8 and B is NR 9 R 10 , wherein R 7 , R 8 , R 9 and R 10 independently represent H or alkyl, and A and B are linked by an alkylene chain, optionally substituted in or on the alkylene chain, or p is 1, A is NR 7 and B is NR 9 R 10 , wehrein R 7 , R 9 and R 10 are as previously defined, and A and B are linked by an alkylene chain, optionally substituted.

1 - 18 . (canceled)  
   
   
       19 . A method of treating cancer, comprising administering to a subject a therapeutically effective amount of a compound of formula (I):  
     
       
         
         
             
             
         
       
     
     wherein: 
 R 1 , R 2 , R 3 , R 4 , R 5  and R 6  independently represent H, alkyl, cycloalkyl, —CO 2 R′, aryl or alkylaryl, which latter two groups are optionally substituted on the aromatic ring;  
 R′ represents alkyl, cycloalkyl, aryl or alkaryl;  
 X is halo, H 2 O, (R′)(R″)SO, R′CO 2   −  or (R′)(R″)C═O, where R″ represents alkyl, cycloalkyl, aryl or alkylaryl;  
 Y is a counterion;  
 m is 0 or 1;  
 q is 1,2or 3;  
 C′ is C 1  to C 12  alkylene, optionally substituted in or on the alkylene chain, bound to two A groups;  
 p is 0 or I and r is 1 when p is 0 and r is 2 when p is 1; and  
 A and B are: each independently: R 11 —CN wherein R 11  represents alkyl; or B is halo and A is a 4-substitued pyridine, optionally substituted at one or more of the carbon atoms of the pyridine ring; or p is 0, A is NR 7 R 8  and B is NR 9 R 10 , wherein R 7 , R 8 , R 9  and R 10  independently represent H, alkyl or cycloalkyl, and A and B are linked by an alkylene chain, optionally substituted in or on the alkylene chain; or p is 1, A is NR 7  and B is NR 9 R 10 , wherein R 7 , R 9  and R 10  are as previously defined, and A and B are linked by an alkylene chain, optionally substituted.  
 
   
   
       20 . The method as claimed in  claim 19 , wherein R 2 , R 3 , R 4 , R 5  and R 6  all represent H.  
   
   
       21 . The method as claimed in  claim 19 , wherein R 1  is H.  
   
   
       22 . The method as claimed in  claim 19 , wherein R 1  is 2-propyl and R 4  is methyl.  
   
   
       23 . The method as claimed in  claim 19 , wherein R 1  is phenyl.  
   
   
       24 . The method as claimed in  claim 19 , wherein R 1  is —CO 2 CH 3 .  
   
   
       25 . The method as claimed in  claim 19 , wherein A and B are both R 11 —CN and R 11  represents alkyl.  
   
   
       26 . The method as claimed in  claim 19 , wherein one of A and B is a 4-substituted pyridine and the other is halo.  
   
   
       27 . The method as claimed in  claim 19 , wherein A and B together represent NR 7 R 8 —(CR 12 R 3 ) n —NR 9 R 10 , wherein R 12  and R 13  are hydrogen, or together with the carbon to which they are attached form a carbocyclic ring, and n is an integer from 1 to 4.  
   
   
       28 . The method as claimed in  claim 27 , wherein R 7 , R 8 , R 9  and R 10  all represent H.  
   
   
       29 . The method as claimed in  claim 27 , wherein R 12  and R 13  are both H and n is 2.  
   
   
       30 . The method as claimed in  claim 27 , wherein p is 0.  
   
   
       31 . The method as claimed in  claim 27 , wherein R 8  is absent, p is 1 and C′ is C 4  to C 10  straight chain alkylene.