Substituted benzimidazoles and their use for inducing apoptosis

Abstract

The invention relates to compounds of formula (I) wherein R represents aryl or heteroaryl, X is a bond, a carbonyl group, a derivative of a carbonyl group, an ethylene group or an ethylenecarbonyl group, R 1 is optionally substituted amino or hydroxy, and the substituents R 2 to R 6 have the meanings given in the specification, to methods of synthesis of such compounds, to pharmaceutical compositions containing compounds of formula (I), to intermediates, to the use of a compounds of formula (I) as a medicament and for the preparation of a pharmaceutical composition for the treatment of neoplastic and autoimmune diseases, and to methods of treatment of neoplastic and autoimmune diseases using such compounds of formula (I) or of pharmaceutical compositions containing same.

1 . A compound of formula (I)  
     
       
         
         
             
             
         
       
     
     wherein 
 R represents aryl or heteroaryl optionally substituted by up to four substituents independently selected from  
 alkyl, cycloalkyl, cycloalkyl-lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy-lower alkoxy-lower alkyl, halo-lower alkoxy-lower alkyl, acyloxy-lower alkyl, heterocyclyl, heterocyclyl-lower alkyl, optionally substituted phenyl, optionally substituted phenyl-lower alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-lower alkyl, optionally substituted alkenyl, optionally substituted alkinyl, hydroxy, lower alkoxy, optionally substituted alkenyloxy, optionally substituted alkinyloxy, cycloalkoxy, halo-lower alkoxy, cycloalkyl-lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, heterocyclyloxy, heterocyclyl-lower alkoxy, optionally substituted phenyloxy, optionally substituted phenyl-lower alkoxy, optionally substituted heteroaryloxy, optionally substituted heteroaryl-lower alkoxy, sulfamoyloxy, carbamoyloxy, lower alkylcarbonyloxy,  
 amino, monoalkylamino, dialkylamino, aminocarbonylamino wherein each of the two amino groups is optionally substituted by alkyl, alkenyl, alkinyl or alkoxy-lower alkyl, heterocyclylcarbonylamino wherein heterocyclyl is bound via a nitrogen atom, aminosulfonylamino wherein each of the two amino groups is optionally substituted by alkyl, alkenyl, alkinyl or alkoxy-lower alkyl, heterocyclylsulfonylamino wherein heterocyclyl is bound via a nitrogen atom, lower alkoxycarbonylamino, lower alkylcarbonylamino wherein alkyl is optionally substituted by one or two substituents selected from optionally substituted phenyl, guanidyl, halogen, cyano, alkoxy, optionally substituted phenoxy, alkylmercapto and optionally substituted amino; lower alkenylcarbonylamino wherein alkenyl is optionally substituted by one or two substituents selected from lower alkyl, halo-lower alkyl, optionally substituted phenyl, halogen, cyano, alkoxy and optionally substituted amino; amino-lower alkyl or amino-lower alkylamino, wherein the nitrogen atom is unsubstituted or substituted by one or two substitutents selected from lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, optionally substituted phenyl, optionally substituted phenyl-lower alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-lower alkyl and lower alkylcarbonyl, or wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, cycloalkylcarbonyl, optionally substituted phenylcarbonyl, optionally substituted heteroarylcarbonyl, heterocyclylcarbonyl,  
 carboxy, lower alkoxycarbonyl, hydroxy-lower alkoxycarbonyl, lower alkoxy-lower alkoxycarbonyl, optionally substituted phenyl-lower alkoxycarbonyl, cyano, lower alkylmercapto, optionally substituted phenylmercapto, lower alkylsulfinyl, halo-lower alkylsulfinyl, optionally substituted phenylsulfinyl, lower alkylsulfonyl, halo-lower alkylsulfonyl, optionally substituted phenylsulfonyl, aralkylsulfonyl, halogen, and nitro; and wherein two adjacent substituents together with the atoms of aryl or heteroaryl may form a 5 or 6 membered carbocyclic or heterocyclic ring;  
 X represents a bond; oxygen; a group C═Y, wherein Y stands for oxygen, nitrogen substituted by hydroxy, alkoxy or optionally substituted amino; a group —CH═CH—(C═O) n — or —(C═O) n —CH═CH— wherein n is 0 or 1; or a group CR 7 R 8 ;  
 Q represents N or CR 9 ;  
 R 1  represents a group NR 10 R 11  or OR 12 ;  
 R 2  represents hydrogen, lower alkyl or amino;  
 R 3 , R 4 , R 5  and R 6 , independently of each other, represent hydrogen, lower alkyl, halo-lower alkyl, cyano-lower alkyl, carboxy-lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy-lower alkoxy-lower alkyl, halo-lower alkoxy-lower alkyl, heterocyclyl, heterocyclyl-lower alkyl, optionally substituted phenyl, optionally substituted phenyl-lower alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-lower alkyl, optionally substituted alkenyl, optionally substituted alkinyl,  
 hydroxy, lower alkoxy, halo-lower alkoxy, cycloalkoxy, cycloalkyl-lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, heterocyclyloxy, heterocyclyl-lower alkoxy, optionally substituted phenyloxy, optionally substituted phenyl-lower alkoxy, optionally substituted heteroaryloxy, optionally substituted heteroaryl-lower alkoxy, amino, carbamoyl, sulfamoyl, amino-lower alkyl or amino-lower alkylamino, wherein in each case the nitrogen atom is unsubstituted or substituted by one or two substitutents selected from lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, optionally substituted phenyl, optionally substituted phenyl-lower alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-lower alkyl and lower alkylcarbonyl, or wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl,  
 lower alkylcarbonyl, cycloalkylcarbonyl, optionally substituted phenylcarbonyl, optionally substituted heteroarylcarbonyl, heterocyclylcarbonyl,  
 carboxy, lower alkoxycarbonyl, hydroxy-lower alkoxycarbonyl, lower alkoxy-lower alkoxycarbonyl, optionally substituted phenyl-lower alkoxycarbonyl, cyano, lower alkylmercapto, optionally substituted phenylmercapto, lower alkylsulfinyl, halo-lower alkylsulfinyl, optionally substituted phenylsulfinyl, lower alkylsulfonyl, halo-lower alkylsulfonyl, optionally substituted phenylsulfonyl, aralkylsulfonyl, halogen, or nitro,  
 or R 3  and R 4 , R 4  and R 5 , or R 5  and R 6  together with the atoms of the phenyl ring form a 5 or 6 membered carbocyclic or heterocyclic ring;  
 R 7  represents hydrogen, lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, lower alkenyl, lower alkinyl, optionally substituted phenyl, lower alkoxy, lower alkenyloxy, lower alkinyloxy;  
 R 8  represents hydrogen, lower alkyl, hydroxy, lower alkoxy or lower alkenyloxy, or  
 R 7  and R 8  together with the carbon they are bound to form a 5 or 6 membered carbocyclic or heterocyclic ring;  
 R 9  represents hydrogen, lower alkyl or amino;  
 R 10  and R 11 , independently of each other, represent hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, hydroxyalkyl, alkoxyalkyl, hydroxyalkoxyalkyl, alkoxyalkoxyalkyl, cyanoalkyl, carboxyalkyl, optionally substituted alkenyl, optionally substituted alkinyl, or lower alkylcarbonyl wherein lower alkyl is optionally substituted by one or two substitutents selected from aryl, optionally substituted amino, alkoxy and aryloxy;  
 or R 10  and R 11  together with the atom they are bound to form heterocyclyl;  
 R 12  is hydrogen, lower alkyl, acyl or aminocarbonyl wherein amino is unsubstituted or substituted by lower alkyl;  
 tautomers and salts thereof.  
 
   
   
       2 . The compound of formula (I) according to  claim 1  wherein 
 R represents aryl or heteroaryl optionally substituted by up to four substituents independently selected from    alkyl, cycloalkyl, cycloalkyl-lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy-lower alkoxy-lower alkyl, halo-lower alkoxy-lower alkyl, acyloxy-lower alkyl, heterocyclyl, heterocyclyl-lower alkyl, optionally substituted phenyl, optionally substituted phenyl-lower alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-lower alkyl, optionally substituted alkenyl, optionally substituted alkinyl, hydroxy, lower alkoxy, optionally substituted alkenyloxy, optionally substituted alkinyloxy, cycloalkoxy, halo-lower alkoxy, cycloalkyl-lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, heterocyclyloxy, heterocyclyl-lower alkoxy, optionally substituted phenyloxy, optionally substituted phenyl-lower alkoxy, optionally substituted heteroaryloxy, optionally substituted heteroaryl-lower alkoxy, sulfamoyloxy, carbamoyloxy, lower alkylcarbonyloxy,    amino, monoalkylamino, dialkylamino, aminocarbonylamino wherein each of the two amino groups is optionally substituted by alkyl, alkenyl, alkinyl or alkoxy-lower alkyl, heterocyclylcarbonylamino wherein heterocyclyl is bound via a nitrogen atom, aminosulfonylamino wherein each of the two amino groups is optionally substituted by alkyl, alkenyl, alkinyl or alkoxy-lower alkyl, heterocyclylsulfonylamino wherein heterocyclyl is bound via a nitrogen atom, lower alkoxycarbonylamino, lower alkylcarbonylamino wherein alkyl is optionally substituted by one or two substituents selected from optionally substituted phenyl, guanidyl, halogen, cyano, alkoxy, optionally substituted phenoxy, alkylmercapto and optionally substituted amino; lower alkenylcarbonylamino wherein alkenyl is optionally substituted by one or two substituents selected from lower alkyl, halo-lower alkyl, optionally substituted phenyl, halogen, cyano, alkoxy and optionally substituted amino; amino-lower alkyl or amino-lower alkylamino, wherein the nitrogen atom is unsubstituted or substituted by one or two substitutents selected from lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, optionally substituted phenyl, optionally substituted phenyl-lower alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-lower alkyl and lower alkylcarbonyl, or wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, cycloalkylcarbonyl, optionally substituted phenylcarbonyl, optionally substituted heteroarylcarbonyl, heterocyclylcarbonyl,    carboxy, lower alkoxycarbonyl, hydroxy-lower alkoxycarbonyl, lower alkoxy-lower alkoxycarbonyl, optionally substituted phenyl-lower alkoxycarbonyl, cyano, lower alkylmercapto, optionally substituted phenylmercapto, lower alkylsulfinyl, halo-lower alkylsulfinyl, optionally substituted phenylsulfinyl, lower alkylsulfonyl, halo-lower alkylsulfonyl, optionally substituted phenylsulfonyl, aralkylsulfonyl, halogen, and nitro; and wherein two adjacent substituents together with the atoms of aryl or heteroaryl may form a 5 or 6 membered carbocyclic or heterocyclic ring;    X represents a bond; oxygen; a group C═Y, wherein Y stands for oxygen, nitrogen substituted by hydroxy, alkoxy or optionally substituted amino; a group —CH═CH—(C═O) n — or —(C═O) n —CH═CH— wherein n is 0 or 1; or a group CR 7 R 8 ;    Q represents N or CR 9 ;    R 1  represents a group NR 10 R 11  or OR 12 ;    R 2  represents hydrogen, lower alkyl or amino;    R 3 , R 4 , R 5  and R 6 , independently of each other, represent hydrogen, lower alkyl, halo-lower alkyl, cyano-lower alkyl, carboxy-lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy-lower alkoxy-lower alkyl, halo-lower alkoxy-lower alkyl, heterocyclyl, heterocyclyl-lower alkyl, optionally substituted phenyl, optionally substituted phenyl-lower alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-lower alkyl, optionally substituted alkenyl, optionally substituted alkinyl,    hydroxy, lower alkoxy, halo-lower alkoxy, cycloalkoxy, cycloalkyl-lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, heterocyclyloxy, heterocyclyl-lower alkoxy, optionally substituted phenyloxy, optionally substituted phenyl-lower alkoxy, optionally substituted heteroaryloxy, optionally substituted heteroaryl-lower alkoxy,    amino, carbamoyl, sulfamoyl, amino-lower alkyl or amino-lower alkylamino, wherein in each case the nitrogen atom is unsubstituted or substituted by one or two substitutents selected from lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, optionally substituted phenyl, optionally substituted phenyl-lower alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-lower alkyl and lower alkylcarbonyl, or wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl,    lower alkylcarbonyl, cycloalkylcarbonyl, optionally substituted phenylcarbonyl, optionally substituted heteroarylcarbonyl, heterocyclylcarbonyl,    carboxy, lower alkoxycarbonyl, hydroxy-lower alkoxycarbonyl, lower alkoxy-lower alkoxycarbonyl, optionally substituted phenyl-lower alkoxycarbonyl, cyano,    lower alkylmercapto, optionally substituted phenylmercapto, lower alkylsulfinyl, halo-lower alkylsulfinyl, optionally substituted phenylsulfinyl, lower alkylsulfonyl, halo-lower alkylsulfonyl, optionally substituted phenylsulfonyl, aralkylsulfonyl, halogen, or nitro,    or R 3  and R 4 , R 4  and R 5 , or R 5  and R 6  together with the atoms of the phenyl ring form a 5 or 6 membered carbocyclic or heterocyclic ring;    and pharmaceutically acceptable salts thereof; for use as medicaments.    R 7  represents hydrogen, lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, lower alkenyl, lower alkinyl, optionally substituted phenyl, lower alkoxy, lower alkenyloxy, lower alkinyloxy;    R 8  represents hydrogen, lower alkyl, hydroxy, lower alkoxy or lower alkenyloxy, or    R 7  and R 8 together with the carbon they are bound to form a 5 or 6 membered carbocyclic or heterocyclic ring;    R 9  represents hydrogen, lower alkyl or amino;    R 10  and R 11 , independently of each other, represent hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, hydroxyalkyl, alkoxyalkyl, hydroxyalkoxyalkyl, alkoxyalkoxyalkyl, cyanoalkyl, carboxyalkyl, optionally substituted alkenyl, optionally substituted alkinyl, or lower alkylcarbonyl wherein lower alkyl is optionally substituted by one or two substitutents selected from aryl, optionally substituted amino, alkoxy and aryloxy;    or R 10  and R 11  together with the atom they are bound to form heterocyclyl;    R 12  is hydrogen or lower alkyl;    tautomers and salts thereof.    
   
   
       3 . The compound of formula (I) according to  claim 1  wherein 
 R represents phenyl, naphthyl, thienyl, furyl, thiazolyl, oxadiazolyl, thiadiazolyl, imidazolyl, pyrazolyl, pyridinyl, pyrimidinyl, benzothienyl, benzofuryl, indolyl, benzisoxazolyl, each optionally substituted by up to four substituents independently selected from alkyl, cycloalkyl, cycloalkyl-lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, lower alkoxy-lower alkoxy-lower alkyl, halo-lower alkoxy-lower alkyl, acyloxy-lower alkyl, heterocyclyl, heterocyclyl-lower alkyl, optionally substituted phenyl, optionally substituted phenyl-lower alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-lower alkyl, optionally substituted alkenyl, optionally substituted alkinyl, hydroxy, lower alkoxy, optionally substituted alkenyloxy, optionally substituted alkinyloxy, cycloalkoxy, halo-lower alkoxy, cycloalkyl-lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, heterocyclyloxy, heterocyclyl-lower alkoxy, optionally substituted phenyloxy, optionally substituted phenyl-lower alkoxy, optionally substituted heteroaryloxy, optionally substituted heteroaryl-lower alkoxy, sulfamoyloxy, carbamoyloxy, lower alkylcarbonyloxy,    amino, monoalkylamino, dialkylamino, aminocarbonylamino wherein each of the two amino groups is optionally substituted by alkyl, alkenyl, alkinyl or alkoxy-lower alkyl, heterocyclylcarbonylamino wherein heterocyclyl is bound via a nitrogen atom, aminosulfonylamino wherein each of the two amino groups is optionally substituted by alkyl, alkenyl, alkinyl or alkoxy-lower alkyl, heterocyclylsulfonylamino wherein heterocyclyl is bound via a nitrogen atom, lower alkoxycarbonylamino, lower alkylcarbonylamino wherein alkyl is optionally substituted by one or two substituents selected from optionally substituted phenyl, guanidyl, halogen, cyano, alkoxy, optionally substituted phenoxy, alkylmercapto and optionally substituted amino; lower alkenylcarbonylamino wherein alkenyl is optionally substituted by one or two substituents selected from lower alkyl, halo-lower alkyl, optionally substituted phenyl, halogen, cyano, alkoxy and optionally substituted amino; amino-lower alkyl or amino-lower alkylamino, wherein the nitrogen atom is unsubstituted or substituted by one or two substitutents selected from lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, optionally substituted phenyl, optionally substituted phenyl-lower alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-lower alkyl and lower alkylcarbonyl, or wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, cycloalkylcarbonyl, optionally substituted phenylcarbonyl, optionally substituted heteroarylcarbonyl, heterocyclylcarbonyl,    lower alkylsulfinyl, halo-lower alkylsulfinyl, lower alkylsulfonyl, halo-lower alkylsulfonyl, halogen, and nitro;    and wherein two adjacent substituents together with the atoms of aryl or heteroaryl may form a 5 or 6 membered carbocyclic or heterocyclic ring;    X represents oxygen; a group C═Y, wherein Y stands for oxygen, nitrogen substituted by hydroxy, alkoxy or optionally substituted amino; or a group —CH═CH—(C═O) n — or —(C═O) n —CH═CH— wherein n is 0 or 1;    Q represents N or CR 9 ;    R 1  represents a group NR 10 R 11  or OR 12 ;    R 2  represents hydrogen, lower alkyl or amino;    R 3 , R 4 , R 5  and R 6 , independently of each other, represent hydrogen, lower alkyl, halo-lower alkyl, cyano-lower alkyl, carboxy-lower alkyl, hydroxy, lower alkoxy, halo-lower alkoxy, cycloalkoxy, cycloalkyl-lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, heterocyclyloxy, heterocyclyl-lower alkoxy, optionally substituted phenyloxy, optionally substituted phenyl-lower alkoxy, optionally substituted heteroaryloxy, optionally substituted heteroaryl-lower alkoxy,    amino, carbamoyl, sulfamoyl, amino-lower alkyl or amino-lower alkylamino, wherein in each case the nitrogen atom is unsubstituted or substituted by one or two substitutents selected from lower alkyl, cycloalkyl, cycloalkyl-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, optionally substituted phenyl, optionally substituted phenyl-lower alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-lower alkyl and lower alkylcarbonyl, or wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl,    lower alkylcarbonyl, cycloalkylcarbonyl, optionally substituted phenylcarbonyl, optionally substituted heteroarylcarbonyl, heterocyclylcarbonyl, carboxy, lower alkoxycarbonyl, hydroxy-lower alkoxycarbonyl, lower alkoxy-lower alkoxycarbonyl, optionally substituted phenyl-lower alkoxycarbonyl, cyano, lower alkylsulfinyl, halo-lower alkylsulfinyl, lower alkylsulfonyl, halo-lower alkylsulfonyl, halogen, or nitro;    or R 3  and R 4 , R 4  and R 5 , or R 5  and R 6  together represent methylenedioxy;    R 9  represents hydrogen;    R 10  and R 11 , independently of each other, represent hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, hydroxyalkyl, alkoxyalkyl, hydroxyalkoxyalkyl, alkoxyalkoxyalkyl, cyanoalkyl, carboxyalkyl, optionally substituted alkenyl, optionally substituted alkinyl, or lower alkylcarbonyl wherein lower alkyl is optionally substituted by one or two substitutents selected from aryl, optionally substituted amino, alkoxy and aryloxy;    or R 10  and R 11  together with the atom they are bound to form heterocyclyl;    R 2  is hydrogen;    tautomers and pharmaceutically acceptable salts thereof.    
   
   
       4 . The compound of formula (I) according to  claim 1  wherein 
 R represents phenyl, naphthyl, thienyl, furyl, thiazolyl, oxadiazolyl, thiadiazolyl, imidazolyl, pyrazolyl, pyridinyl, pyrimidinyl, benzothienyl, benzofuryl, indolyl, benzisoxazolyl, optionally substituted by up to four substituents independently selected from alkyl, halo-lower alkyl, phenyl, optionally substituted heteroaryl, lower alkoxy, optionally substituted alkenyloxy, optionally substituted alkinyloxy, lower alkoxy-lower alkoxy, amino, monoalkylamino, dialkylamino, aminocarbonylamino wherein each of the two amino groups is optionally substituted by alkyl, alkenyl, alkinyl or alkoxy-lower alkyl, heterocyclylcarbonylamino wherein heterocyclyl is bound via a nitrogen atom, aminosulfonylamino wherein each of the two amino groups is optionally substituted by alkyl, alkenyl, alkinyl or alkoxy-lower alkyl, heterocyclylsulfonylamino wherein heterocyclyl is bound via a nitrogen atom, lower alkoxycarbonylamino, lower alkylcarbonylamino wherein alkyl is optionally substituted by alkoxy or optionally substituted amino; lower alkenylcarbonylamino wherein alkenyl is optionally substituted by alkoxy or optionally substituted amino; lower alkylsulfinyl, halo-lower alkylsulfinyl, lower alkylsulfonyl, halo-lower alkylsulfonyl and halogen;    and wherein two adjacent substituents together with the atoms of aryl or heteroaryl may form a 5 or 6 membered carbocyclic or heterocyclic ring;    X represents oxygen or a group C═Y, wherein Y stands for oxygen;    Q represents N or CR 9 ;    R 1  represents a group NR 10 R 11  or OR 12 ;    R 2  represents hydrogen, lower alkyl or amino;    R 3 , R 4 , R 5  and R 6 , independently of each other, represent hydrogen, lower alkyl, halo-lower alkyl, cyano-lower alkyl, carboxy-lower alkyl, hydroxy, lower alkoxy, carboxy, lower alkoxycarbonyl, cyano or halogen;    R 9  represents hydrogen;    R 10  and R 11 , independently of each other, represent hydrogen, cyano-lower alkyl, carboxy-lower alkyl or lower alkylcarbonyl;    R 12  is hydrogen;    tautomers and pharmaceutically acceptable salts thereof.    
   
   
       5 . The compound of formula (I) according to  claim 1  wherein 
 R represents phenyl, pyridinyl or pyrimidinyl, each optionally substituted by up to four substituents independently selected from alkyl, optionally substituted heteroaryl, lower alkoxy, optionally substituted alkenyloxy, lower alkoxy-lower alkoxy, amino, monoalkylamino, dialkylamino, aminocarbonylamino wherein each of the two amino groups is optionally substituted by alkyl, alkenyl, alkinyl or alkoxy-lower alkyl, heterocyclylcarbonylamino wherein heterocyclyl is bound via a nitrogen atom; lower alkylsulfinyl, halo-lower alkylsulfinyl, lower alkylsulfonyl, halo-lower alkylsulfonyl and halogen; and wherein two adjacent substituents together with the atoms of aryl or heteroaryl may form a 5 or 6 membered carbocyclic or heterocyclic ring;    X represents oxygen or a group C═Y, wherein Y stands for oxygen;    Q represents N or CR 9 ;    R 1  represents a group NR 10 R 11 ;    R 2  represents hydrogen;    R 3 , R 4 , R 5  and R 6 , independently of each other, represent hydrogen, lower alkyl, halo-lower alkyl, hydroxy, lower alkoxy, carboxy, lower alkoxycarbonyl, cyano or halogen;    R 9  represents hydrogen;    R 10  represents hydrogen, hydroxy-lower alkyl, cyano-lower alkyl or lower alkylcarbonyl;    R 11  represents hydrogen;    tautomers and pharmaceutically acceptable salts thereof.    
   
   
       6 . A compound of formula (I) according to  claim 1  wherein 
 R represents 3,4-dimethylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-aminophenyl, 3-amino-4-chlorophenyl or 2-amino-5-pyridiyl;    X represents a group C═Y, wherein Y stands for oxygen;    Q represents N;    R 1  represents a group NR 10 R 11 ;    R 2 , R 3 , R 4 , R 5  and R 6  represent hydrogen;    R 10  represents hydrogen or cyanoethyl;    R 11  represents hydrogen;    tautomers and pharmaceutically acceptable salts thereof.    
   
   
       7 . A compound of formula (I) according to  claim 1  wherein 
 R represents 3,4-dimethylphenyl, 4-methoxyphenyl or 4-chlorophenyl;    X represents a group C═Y, wherein Y stands for oxygen;    Q represents CR 9 ;    R 1  represents a group NR 10 R 11 ;    R 2 , R 3 , R 4 , R 5 , R 6 , R 9 , R 10  and R 11  represent hydrogen;    tautomers and pharmaceutically acceptable salts thereof.    
   
   
       8 . A compound of formula (I) according to  claim 1  for use as a medicament.  
   
   
       9 . A method for the preparation of a compound of formula (I) according to  claim 1 , wherein a compound of formula (II)  
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2 , R 3 , R 4 , R 5  and R 6  are defined as for formula (I), or a derivative thereof with functional groups in protected form and/or a salt thereof, is alkylated with a halide of the formula (III)  
       R—X—CH 2 —Z (III)  
     wherein R is as defined for formula (I) and Z is a nucleophilic leaving group; 
 any protecting groups in a protected derivative of a compound of the formula (I) are removed;  
 and, if so desired, an obtainable compound of formula (I) is converted into another compound of formula (I), a free compound of formula (I) is converted into a salt, an obtainable salt of a compound of formula (I) is converted into the free compound or another salt, and/or a mixture of isomeric compounds of formula (I) is separated into the individual isomers.  
 
   
   
       10 . A compound of formula (II)  
     
       
         
         
             
             
         
       
     
     wherein 
 Q represents CR 9 ;  
 R 1  represents a group NR 10 R 11 ;  
 R 2 , R 3 , R 4 , R 5  and R 6  represent hydrogen;  
 R 9 , R 10  and R 11  represent hydrogen; tautomers and salts thereof.  
 
   
   
       11 . A pharmaceutical composition comprising a compound of formula (I) according to  claim 1  and a pharmaceutically acceptable carrier.  
   
   
       12 . Use a compound of formula (I) according to  claim 1 , a prodrug or a pharmaceutically acceptable salt of such a compound for the preparation of a pharmaceutical composition for the treatment of a neoplastic disease, autoimmune disease, transplantation related pathology and/or degenerative disease.  
   
   
       13 . A method of treatment of a neoplastic disease, autoimmune disease, transplantation related pathology and/or degenerative disease, which comprises administering a compound of formula (I) according to  claim 1 , a prodrug or a pharmaceutically acceptable salt of such a compound, in a quantity effective against said disease, to a warm-blooded animal requiring such treatment.