N-aryl (thio) anthranilic acid amide derivatives, their preparation and their use as VEGF receptor tyrosine kinase inhibitors

Abstract

Described are compunds of formula (I), wherein W is O or S; X is NR 8 ; Y is CR 9 R 10 —(CH 2 ) n wherein R 9 and R 10 are independently of each other hydrogen or lower alkyl, and n is an integer of from and including 0 to and including 3; or Y is SO 2 ; R 1 is aryl; R 2 is a mono- or bicyclic heteroaryl group comprising one or more ring nitrogen atoms with the exception that R 2 cannot represent 2-phthalimidyl, and in case of Y═SO 2 cannot represent 2,1,3-benzothiadiazol-4-yl; any of R 3 , R 4 , R 5 and R 6 , independently of the other, is H or a substituent other than hydrogen; and R 7 and R 8 , independently of each, other, are H or lower alkyl; or a N-oxide or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical product for the treatment of a neoplastic disease which responds to an inhibition of the VEGF receptor tyrosine kinase activity. The compounds of formula (I) can be used for the treatment e.g. of a neoplastic disease, such as a tumor disease, of retinopathy and age-related macular degeneration.

1 - 17 . (canceled)  
   
   
       18 . A method for treating a neoplastic disease which responds to an inhibition of the VEGF receptor tyrosine kinase activity comprising administering a compound of formula I,  
     
       
         
         
             
             
         
       
     
     wherein 
 W is O or S;  
 X is NR 8 ;  
 Y is CR 9 R 10 —(CH 2 ) n  wherein 
 R 9  and R 10  are independently of each other hydrogen or lower alkyl, and  
 n is an integer of from and including 0 to and including 3; or  
 
 Y is SO 2 ;  
 R 1  is aryl;  
 R 2  is an imidazoly;  
 any of R 3 , R 4 , R 5  and R 6 , independently of the other, is H or a halogen or an alkyl group; and  
 R 7  and R 8 , independently of each other, are H or lower alkyl;  
 or a N-oxide or a pharmaceutically acceptable salt thereof.  
 
   
   
       19 . A method for the treatment of retinopathy or age-related macula degeneration comprising administering 
 a compound of formula I,                          wherein    W is O or S;    X is NR 8 ;    Y is CR 9 R 10 —(CH 2 ) n  wherein 
 R 9  and R 10  are independently of each other hydrogen or lower alkyl, and  
 n is an integer of from and including 0 to and including 3; or  
   Y is SO 2 ;    R 1  is aryl;    R 2  is an imidazoly;    any of R 3 , R 4 , R 5  and R 6 , independently of the other, is H or a halogen or an alkyl group; and    R 7  and R 8 , independently of each other, are H or lower alkyl;    or a N-oxide or a pharmaceutically acceptable salt thereof.    
   
   
       20 . A method for the treatment of a neoplastic disease according to  claim 18  wherein the compound of formula I is administered in a quantity effective against the said disease, to a warm-blooded animal requiring such treatment.  
   
   
       21 . A method for the treatment of retinopathy or age-related macular degeneration according to  claim 19  wherein the compound of formula I is administered in a quantity effective against said diseases, to a warm-blooded animal requiring such treatment.