Pharmaceutically Active Compounds

Abstract

and pharmaceutical compositions containing such compounds. The compounds and compositions have valuable pharmaceutical properties. In particular, they may be used for the treatment of cancer. Novel intermediates and novel methods of preparation are also disclosed.

1 . A compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein
 Q 1 , Q 2  and Q 3  all represent nitrogen atoms; 
 
         A represents an optionally substituted five- or six-membered aromatic ring; 
         R 1  represents an aliphatic carbocyclic or heterocyclic ring, optionally substituted by —(C═O) x NR a R b , —OR c , —SO 2 R g  or optionally substituted alkyl, in which
 x is 0 or 1; 
 R a  and R b  independently represent (a) H, (b) optionally substituted alkyl, (c) optionally substituted cycloalkyl, (d) optionally substituted heterocycloalkyl, (e) —(C═O)R d , or (f) —SO 2 R e , wherein R d  and R e  independently represent (i) optionally substituted alkyl, (ii) optionally substituted alkoxy, or (iii) optionally substituted cycloalkyl; or R a  and R b  together with the nitrogen atom to which they are attached form an optionally substituted aromatic or aliphatic heterocyclic ring; 
 R c  represents optionally substituted alkyl; 
 and 
 R g  represents optionally substituted cycloalkyl; 
 
         R 2  represents H, optionally substituted alkyl or halo; 
         R 3  represents an optionally substituted aryl or heteroaryl ring; 
         R 5  and R 6  independently represent H or optionally substituted alkyl; or R 5  and R 6  together with the carbon atom to which they are attached form an optionally substituted cycloalkyl ring, optionally containing a heteroatom; 
         and the corresponding N-oxides; and pharmaceutically acceptable salts and solvates of such compounds and their N-oxides and prodrugs. 
       
     
     
         2 .- 5 . (canceled) 
     
     
         6 . A compound according to  claim 1 , wherein A represents an optionally substituted five- or six-membered heterocyclic ring. 
     
     
         7 .- 9 . (canceled) 
     
     
         10 . A compound according to  claim 1 , wherein A represents optionally substituted phenyl. 
     
     
         11 .- 13 . (canceled) 
     
     
         14 . A compound according to  claim 1 , wherein R 1  represents a six-membered aliphatic carbocyclic or heterocyclic ring, optionally substituted by —(C═O) x NR a R b , —SO 2 R g  or optionally substituted alkyl. 
     
     
         15 .- 40 . (canceled) 
     
     
         41 . A compound according to  claim 14 , wherein R a  and R b , together with the nitrogen atom to which they are attached, form an optionally substituted 5- or 6-membered aromatic or aliphatic heterocyclic ring. 
     
     
         42 . A compound according to  claim 41 , wherein the aromatic or aliphatic heterocyclic ring is optionally substituted by oxo or alkyl. 
     
     
         43 .- 64 . (canceled) 
     
     
         65 . A compound according to  claim 1 , wherein R 3  represents an optionally substituted 5- or 6-membered aryl or heteroaryl ring. 
     
     
         66 .- 79 . (canceled) 
     
     
         80 . A compound according to  claim 1 , wherein R 5  and R 6 , together with the carbon atom to which they are attached, form an optionally substituted cycloalkyl ring, optionally containing a heteroatom. 
     
     
         81 .- 468 . (canceled) 
     
     
         469 . An intermediate compound of formula (II): 
       
         
           
           
               
               
           
         
         wherein
 (a) one of Q 1  and Q 2  represents a nitrogen atom and the other represents CH, or both Q 1  and Q 2  represent nitrogen atoms, and Q 3  represents CH; or 
 (b) Q 1 , Q 2  and Q 3  all represent nitrogen atoms; 
 
         A represents an optionally substituted five- or six-membered aromatic ring; 
         R 1  represents an aliphatic carbocyclic or heterocyclic ring, optionally substituted by —(C═O) x NR a R b , —OR c , —SO 2 R g  or optionally substituted alkyl, in which 
         x is 0 or 1;
 R a  and R b  independently represent (a) H, (b) optionally substituted alkyl, (c) optionally substituted cycloalkyl, (d) optionally substituted heterocycloalkyl, (e) —(C═O)R d , or (f) —SO 2 R e , wherein R d  and R e  independently represent (i) optionally substituted alkyl, (ii) optionally substituted alkoxy, or (iii) optionally substituted cycloalkyl; or R a  and R b  together with the nitrogen atom to which they are attached form an optionally substituted aromatic or aliphatic heterocyclic ring; 
 R c  represents optionally substituted alkyl; 
 
         and 
         R g  represents optionally substituted cycloalkyl; 
         R 2  represents H, optionally substituted alkyl or halo; 
         R 3  represents an optionally substituted aryl or heteroaryl ring; 
         R 5  and R 6  independently represent H or optionally substituted alkyl; or R 5  and R 6  together with the carbon atom to which they are attached form an optionally substituted cycloalkyl ring, optionally containing a heteroatom; 
         and R x  and R y  independently represent H or a protecting group. 
       
     
     
         470 . A compound according to  claim 469 , wherein A is optionally substituted phenyl. 
     
     
         471 . An intermediate compound of formula (IV): 
       
         
           
           
               
               
           
         
         wherein
 (a) one of Q 1  and Q 2  represents a nitrogen atom and the other represents CH, or both Q 1  and Q 2  represent nitrogen atoms, and Q 3  represents CH; or 
 (b) Q 1 , Q 2  and Q 3  all represent nitrogen atoms; 
 
         A represents an optionally substituted five- or six-membered aromatic ring; 
         R 1  represents an aliphatic carbocyclic or heterocyclic ring, optionally substituted by —(C═O) x NR a R b , —OR c , —SO 2 R g  or optionally substituted alkyl, in which 
         x is 0 or 1;
 R a  and R b  independently represent (a) H, (b) optionally substituted alkyl, (c) optionally substituted cycloalkyl, (d) optionally substituted heterocycloalkyl, (e) —(C═O)R d , or (f) —SO 2 R e , wherein R d  and R e  independently represent (i) optionally substituted alkyl, (ii) optionally substituted alkoxy, or (iii) optionally substituted cycloalkyl; or R a  and R b  together with the nitrogen atom to which they are attached form an optionally substituted aromatic or aliphatic heterocyclic ring; 
 R c  represents optionally substituted alkyl; 
 
         and 
         R g  represents optionally substituted cycloalkyl; 
         R 2  represents H, optionally substituted alkyl or halo; 
         R 3  represents an optionally substituted aryl or heteroaryl ring; 
         R 5  and R 6  independently represent H or optionally substituted alkyl; or R 5  and R 6  together with the carbon atom to which they are attached form an optionally substituted cycloalkyl ring, optionally containing a heteroatom; 
         and R x  and R y  independently represent H or a protecting group. 
       
     
     
         472 . A compound according to  claim 471 , wherein A is optionally substituted phenyl. 
     
     
         473 .- 475 . (canceled) 
     
     
         476 . A method of preparing a compound of formula I-30 
       
         
           
           
               
               
           
         
       
       which method comprises esterification of a compound of formula I-27 
       
         
           
           
               
               
           
         
       
       Followed by hydrogenation and reductive amination to yield the compound of I-30. 
     
     
         477 . The method according to  claim 476 , wherein esterification of the compound of formula I-27 is carried out by a Horner-Wadsworth reaction to yield an intermediate of formula I-28 
       
         
           
           
               
               
           
         
       
     
     
         478 . The method according to  claim 477 , wherein the Horner-Wadsworth reaction is carried out using triethyl phosphonoacetate. 
     
     
         479 . The method according to  claim 476 , wherein hydrogenation of the compound of formula I-27 yields an intermediate of formula I-29 
       
         
           
           
               
               
           
         
       
     
     
         480 . The method according to  claim 479 , wherein the hydrogenation is palladium-catalysed hydrogenation. 
     
     
         481 . The method according to  claim 476 , which further comprises the separation of diastereoisomers of the formula I-30 to provide the trans isomer I-24